Đại học Y Dược Huế 2005 = Di Truyền Học Đại Cương

GIO TRNH
DI TRUYN HC I CNG
ThS. Hong Trng Phn (ch bin)

TS. Trng Th Bch Phng TS. Trn Quc Dung
11
Simpo PDF Merge and Split Unregistered Version - http://www.simpopdf.com
Li ni u
n nay, di truyn hc ra i ch mi hn mt trm nm song n
pht trin vi mt tc ht sc nhanh chng. c bit l, trong vng 50
nm li y k t ngy James Watson v Francis Crick khm ph ra cu
trc phn t DNA, 25/4/1953. S hon thnh vic gii m di truyn bi
hai nhm nghin cu ca Marshall Nirenberg v Har Gobind Khorana
vo thng 6 nm 1966 v s ra i ca K thut Di truyn v Cng ngh
DNA ti t hp vo gia thp nin 1970 l hai s kin ni bt nht k t
sau khi sinh hc phn t ra i. K , s hon tt ca D n B gene
Ngi vo thng 4 nm 2003 c xem l mt trong nhng k cng thm
him v i nht ca loi ngi. Ln u tin con ngi c th c c
mt cch y ton b trnh t 3.164.700.000 cp base trong b gene
ca mnh. Tt c nhng s kin ni bt ny minh chng mt iu rng: S
pht trin cng vi nhng thnh tu t c ca di truyn hc trong thi
gian qua qu l v cng to ln!
gp phn i mi ni dung gio trnh Di truyn hc theo hng
cp nht kin thc cng nh phng php dy v hc b mn bc i
hc, chng ti tham cu nhiu ti liu khc nhau v n lc bin son
gio trnh trn tinh thn y. Chng ti hy vng rng gio trnh ny s p
ng c phn no nhu cu ging dy v hc tp ca ging vin v sinh
vin, v cng c th s dng nh mt ti liu tham kho b ch cho gio
vin Sinh hc cc trng THPT trong bi cnh i mi gio dc hin nay.
Ni dung gio trnh gm phn M u cng vi 12 chng bao qut
cc kin thc i cng ca mt gio trnh Di truyn hc. Cc chng 14 cp ch yu ni dung thuc Di truyn hc c in, cc chng 5-10
tp trung vo phn Di truyn hc phn t v chng 12 c xem l phn
nhp mn ca Di truyn hc qun th, cn chng 11 l s kt hp gia
cc kin thc di truyn c in v hin i trn i tng l con ngi.
Cui mi chng u c cc phn Cu hi v Bi tp v Ti liu Tham
kho bn c tin n tp v tra cu.
Gio trnh Di truyn hc c ra i trong khun kh ca D n Gio
dc thuc i hc Hu, v vy mt s kin thc nng cao s c cp
trong mt gio trnh ring, nh: Di truyn Vi sinh vt v ng dng,v
Cng ngh DNA Ti t hp. Bn cnh , mt s thut ng khoa hc
c thng nht s dng bng ting Anh gip ngi hc d dng hn
trong vic tip cn vi thng tin qua sch bo nc ngoi hoc internet.
12
Gio trnh ny do ThS. Hong Trng Phn (ch bin), TS. Trng Th
Bch Phng v TS. Trn Quc Dung l nhng ging vin ang cng tc
ti Khoa Sinh hc cc trng i hc S phm v i hc Khoa hc
thuc i hc Hu bin son, vi s phn cng nh sau:
ThS. Hong Trng Phn bin son phn M u v cc chng 1, 2,
3, 4, 5, 6, 10 v 12;
TS. Trng Th Bch Phng bin son cc chng 7, 8 v 9; v
TS. Trn Quc Dung bin son chng 11.
gio trnh ny kp thi ra mt bn c, chng ti xin trn trng
cm n D n Gio dc i hc Hu ti tr cho vic bin son v xut
bn gio trnh trong khun kh ca D n Gio dc i hc mc B.
Chng ti xin by t lng cm n c bit n GS. TS. Phan C Nhn,
Trng i hc S phm H Ni, dy cng c bn tho v cho nhiu
kin qu bu cng nh khch l chng ti rt nhiu k t khi cng
gio trnh bt u c hnh thnh.
Do kh nng cn hn ch, chc chn gio trnh cn nhiu thiu st.
Chng ti rt mong nhn c s ph bnh v ch bo ca cc ng
nghip v bn c gio trnh c hon chnh hn trong ln in sau.
Hu, ngy 25 thng 6 nm 2005
Cc tc gi
3
Mc lc
11
Li ni u
M u
Hong Trng Phn
I. Khi nim di truyn hc

II. Lc s pht trin ca di truyn hc
III. i tng v cc lnh vc nghin cu ca di truyn hc
IV. Cc phng php nghin cu ca di truyn hc
V.Cc nguyn tc nghin cu v phng php hc tp di truyn hc
VI. Di truyn hc vi cng ngh sinh hc, tin hc v cc vn x hi
13
13
13
17
18
20
21
Chng 1: C s ca Di truyn hc Mendel

Hong Trng Phn
I. Tiu s Mendel - Cha ca di truyn hc

II. i tng v phng php th nghim ca Mendel
1. i tng
2. Phng php
III. Lai mt tnh v nguyn l phn ly
1. Kt qu th nghim lai mt tnh
2. Gii thch v kim chng nguyn l phn ly
3. Nguyn l phn ly v tnh ph bin ca n
IV. Lai hai tnh v nguyn l phn ly c lp
1. Kt qu th nghim lai hai tnh
2. Gii thch v ni dung nguyn l phn ly c lp
V. S di truyn Mendel ngi
1. Cc tnh trng ln
2. Cc tnh trng tri
VI. L thuyt xc sut trong d on v phn tch di truyn hc
1. Mt s khi nim v tnh cht c bn ca xc sut
2. Mt s nguyn l xc sut c bn
VII. Phng php 2 (Chi-square method) trong nh gi ph
hp gia cc s liu quan st v k vng
24
24
25
25
26
26
26
27
28
28
28
29
30
31
32
33
33
34
39
4
Chng 2: M rng v p dng ca Di truyn hc

Mendel
Hong Trng Phn
I. Cc kiu quan h gia cc gene allele i vi mt tnh trng

1. Cc kiu tri hon ton, khng hon ton v ng tri
2. Tc ng ca gene gy cht (lethals)
3. Hin tng a allele (multiple allelism)
II. Tnh a hiu ca gene (pleiotropy)
III. Cc kiu tng tc gia cc gene khng allele
1. Tng tc b tr (complementary)
2. Tng tc t ch (epistasis)
3. Tng tc cng gp- s di truyn a gene v cc tnh trng s lng
IV. Cc mi quan h kiu gene - kiu hnh
1. Thng bin v mc phn ng
2. thm nhp (penetrance) v biu hin (expressivity)
43
43
43
45
46
47
48
49
52
54
59
59
60
Chng 3: C s T bo ca s Sinh sn, Di truyn

v Bin d
Hong Trng Phn
I. Sinh sn hu tnh v tnh n nh ca cc b nhim sc th

II. Hnh thi hc nhim sc th eukaryote
1. Kch thc nhim sc th
2. Tm ng v cc kiu nhim sc th
3. Cc kiu bng nhim sc th (chromosomal bands)
III. Chu k t bo v nguyn phn
1. Chu k t bo (cell cycle)
2. Nguyn phn (mitosis)
IV. Gim phn, s pht sinh giao t v th tinh
1. Gim phn (meiosis)
2. S pht sinh giao t (gametogenesis)
3. S th tinh (fertilization)
V. Cc bin i ca nhim sc th
1. Cc bin i v cu trc nhim sc th
2. Cc bin i v s lng nhim sc th
67
67
70
70
71
72
74
75
76
78
78
81
83
84
84
91
5
Chng 4: Di truyn hc Nhim sc th

Hong Trng Phn 103
I. Trng phi Morgan vi thuyt di truyn nhim sc th

1. Tm quan trng ca rui gim Drosophila
2. Thuyt di truyn nhim sc th
II. S xc nh gii tnh (sex determination)
1. S xc nh gii tnh do kiu gene (GSD)
2. S xc nh gii tnh do mi trng (ESD)
III. S di truyn lin kt vi gii tnh (sex-linked inheritance)
1. c im di truyn ca cc gene trn nhim sc th X v Y
2. S bt hot ca nhim sc th X v mt s vn lin quan
3. Cc tnh trng gii hn bi gii tnh v chu nh hng ca
gii tnh
IV. Lin kt v ti t hp ca cc gene trn mt nhim sc th
1. Khm ph v s trao i cho rui gim
2. Lin kt gene hon ton (gim phn khng c trao i cho)
V. Trao i cho v lp bn di truyn
1. Tn s ti t hp
2. Bn di truyn
3. Trao i cho bn si
VI. Lp bn gene t cc php lai phn tch ba im
1. Trao i cho kp vi vic xc nh trt t v khong cch cc gene
2. nhiu v h s trng hp (coefficient of coincidence)
VII. Lp bn bng phn tch b bn (tetrad analysis)
103
103
107
108
108
112
113
113
117
120
121
122
124
125
125
127
131
134
134
137
139
Chng 5: Bn cht Ho hc v Ti bn ca Vt cht

Di truyn
Hong Trng Phn 147
I. Bng chng vt cht di truyn l cc nucleic acid

1. Cc th nghim bin np vi khun
2. Tnh n nh ca hm lng DNA cc sinh vt bc cao
3. Cc th nghim virus
II. Thnh phn ho hc v cu trc ca DNA
1. Cu trc ca mt nucleotide
147
147
148
149
150
150
6
2. Cu trc chui polynucleotide

3. Thnh phn ho hc v cu trc ca chui xon kp DNA
4. S lc v cc c tnh ho l ca cc nucleic acid
III. Kch thc b gene v tnh phc tp v mt tin ho
1. S lc v b gene ca cc virus, prokaryote v eukaryote
2. Mi quan h gia kch thc b gene v tnh phc tp v tin ho
3. Hm lng DNA v nghch l gi tr C
4. V kch thc DNA cc bo quan
IV. T chc phn t ca cc nhim sc th
1. Cu trc cht nhim sc
2. S lc cc thnh phn DNA trong b gene eukaryote
V. Ti bn DNA (DNA replication)
1. Cc nguyn tc v c im chung ca ti bn DNA
2. Cc enzyme tham gia ti bn DNA
3. C ch ti bn DNA
VI. Ti bn ca cc b gene RNA (RNA genomes)
1. c im ti bn ca cc b gene RNA virus
2. Ti bn ca b gene RNA
3. Phin m ngc
151
152
155
157
157
159
159
161
161
161
163
164
164
167
168
174
174
174
175
Chng 6: Gene v Qu trnh Sinh tng hp Protein

Hong Trng Phn 179
I. S pht trin ca khi nim gene

1. Cc quan nim ca Mendel v Morgan v gene
2. Gi thuyt mt gene - mt enzyme ca Beadle v Tatum
3. Quan nim ca Benzer v cc n v cu trc v chc nng di
truyn
4. Mi quan h gene - cistron cc prokaryote v eukaryote
II. Cu trc v chc nng ca protein
1. Cu trc protein
2. Chc nng protein
III. M di truyn
1. Bng chng di truyn hc v m b ba
2. Gii m di truyn
179
179
180
180
182
186
186
187
189
190
190
7
3. Cc c tnh ca m di truyn
4. Nhng ngoi l so vi m di truyn "ph bin"
5. S linh hot trong vic kt cp anticodon-codon
IV. C ch phin m (transcription) v sa i sau phin m
1. Cc RNA v c im chung ca phin m
2. Cc RNA polymerase ca prokaryote v eukaryote
3. Cc promoter cc prokaryote v eukaryote
4. Cc giai on ca qu trnh phin m
5. S sa i sau phin m i vi cc mRNA eukaryote
V. Cu trc v chc nng ca cc loi RNA v ribosome
1. RNA thng tin (messenger RNA = mRNA)
2. RNA vn chuyn (transfer RNA = tRNA)
3. RNA ribosome (ribosomal RNA = rRNA)
4. Ribosome
VI. C ch dch m (translation)
1. Hot ho amino acid
2. C ch ca qu trnh dch m (tng hp polypeptide)
191
192
193
194
194
196
196
197
198
200
200
200
201
201
202
202
202
Chng 7: S iu ho Biu hin ca Gene

Trng Th Bch Phng 208
I. Cc nguyn l iu ho v mc kim sot phin m

II. iu ho biu hin gene prokaryote
1. Cu trc ca operon
2. iu ho dng tnh operon lactose
3. iu ho m tnh operon tryptophan
4. Phin m d (attenuation)
III. iu ho biu hin gene eukaryote
1. S bin i DNA
2. Cc promoter
3. Nhng trnh t tng cng phin m (enhancer)
4. Trnh t bt hot gene (gene silencing)
5. Promoter chn lc (alternative promoter)
6. Splicing chn lc
202
209
210
212
213
215
217
218
218
219
220
220
220
8
Chng 8: t bin Gene, Ti t hp v cc Yu t

Di truyn Vn ng
I. t bin gene
1. Cc kiu t bin gene
2. Cc tc nhn gy t bin gene
3. C ch phn t ca cc t bin gene
II. Sa cha v bo v DNA
III. Cc yu t di truyn vn ng (transposable genetic elements)
1. Cc yu t di truyn vn ng prokaryote
2. Cc yu t di truyn vn ng eukaryote
223
223
228
228
232
237
237
239
Chng 9: S Di truyn T bo cht
I. S di truyn t bo cht
1. S di truyn ca cc gene lp th
2. S di truyn ca cc gene ty th
3. Hiu qu dng m ln chiu xon v c
II. Lp bn ty th v lp th
1. Lp bn gene ca DNA lp th
2. Lp bn gene ca DNA ty th
III. Di truyn hc phn t cc bo quan
1. Cc b gene lp th (cpDNA)
2. Cc b gene ty th (mtDNA)
245
245
246
249
251
251
253
254
254
255
Chng 10: i cng v Cng ngh DNA Ti t hp

Hong Trng Phn 258
I. Cc cng c chnh ca k thut to dng DNA ti t hp

1. Cc enzyme gii hn
2. Cc vector thng dng trong k thut di truyn
3. Thit lp phn t DNA ti t hp in vitro
II. To dng gene hay DNA ti t hp
1. Nguyn tc chung
2. Quy trnh to dng gene ti t hp
3. Tng hp v to dng cDNA
258
258
260
261
263
263
264
267
9
III. Cc phng php biu hin cc gene c to dng

IV. ng dng ca cng ngh DNA ti t hp
1. Cng ngh DNA ti t hp vi vic nghin cu b gene
2. Cng ngh DNA ti t hp vi y-dc hc
3. K thut di truyn vi cc sinh vt bin i gene
267
269
269
271
274
Chng 11: Di truyn hc Ngi

Trn Quc Dung 278
I. Cc phng php nghin cu di truyn hc ngi

1. Phng php phn tch ph h (genealogy analysis)
2. Phng php nghin cu tr sinh i
3. Phng php di truyn t bo hc ngi
4. Phng php nghin cu qun th
5. Cc k thut sinh hc phn t
II. Cc phng php lp bn di truyn ngi
1. Phn tch lin kt (linkage analysis)
2. Cc phng php lp bn vt l (physical mapping)
III. Nhim sc th Y v cht nhim sc gii tnh ca ngi
1. Nhim sc th Y ca ngi
2. Cht nhim sc th gii tnh ca ngi
IV. S di truyn cc gene tri-ln trn nhim sc th thng v
nhim sc th gii tnh
1. S di truyn cc gene tri-ln trn nhim sc th thng
2. S di truyn cc gene tri-ln trn nhim sc th gii tnh
V. Di truyn y hc
1. Cc bnh di truyn do ri lon chuyn ho v cc bnh nhim
sc th
2. C s di truyn ung th
VI. T vn di truyn y hc
278
278
279
279
279
280
280
280
280
283
283
284
285
285
286
288
288
291
292
Chng 12: Di truyn hc Qun th

Hong Trng Phn 296
I. Cc khi nim c bn ca di truyn hc qun th

1. Qun th (population)
2. Cc h thng giao phi
296
296
296
10
3. Vn gene (gene pool)

4. Tn s kiu gene v tn s allele
II. Nguyn l Hardy-Weinberg v trng thi cn bng ca qun th
1. Nguyn l Hardy-Weinberg
2. Nhng ng dng ca nguyn l Hardy-Weinberg
III. M rng nguyn l Hardy-Weinberg
1. a allele (multiple alleles)
2. Tn s allele sai bit gia hai gii tnh
3. Cc gene lin kt trn X
IV. Ni phi (inbreeding)
1. T th tinh (self-fertilization)
2. H s ni phi (inbreeding coefficient)
3. Tnh ton h s ni phi
V. Cc nhn t tc ng ln thnh phn di truyn qun th
1. t bin
2. Bin ng di truyn ngu nhin
3. Dng gene hay s di nhp c
4. Chn lc t nhin
297
297
299
299
302
305
305
308
309
310
311
312
313
315
315
316
316
318
13
M u
I. Khi nim di truyn hc
Theo quan nim ca Bateson (1906), di truyn hc (genetics) l khoa
hc nghin cu cc c tnh di truyn v bin d vn c ca mi sinh vt
cng vi cc nguyn tc v phng php iu khin cc c tnh .
y, tnh di truyn (heredity) c biu hin s ging nhau gia con ci
vi cha m; v tnh bin d (variability) biu hin s sai khc gia cha
m v con ci cng nh gia cc con ci vi nhau.
Cn lu rng, gene l khi nim cn bn ca di truyn hc cho nn
ni dung ca khi nim gene khng ngng c pht trin cng vi s
pht trin ca di truyn hc.
II. Lc s pht trin ca di truyn hc

S ra i v pht trin ca di truyn hc gn lin vi cng trnh
nghin cu ca Gregor Mendel nm 1865. Tuy nhin, trc thi Mendel
c bit l t th k XVII c mt s s kin quan trng sau y: (1) S ra
i ca knh hin vi s khai bi A.van Leuvenhook (1632-1723); v (2)
Sinh hc bt u pht trin mnh vo th k XIX vi s ra i thuyt t
bo ca M.Schleiden v T.Schwann (1838,1839) v cc thuyt tin ha
ca J.B.Lamarck (1809) v c bit l ca R.C.Darwin (1859). Nhn
chung, quan nim ph bin thi by gi vn l s di truyn cc tnh trng
tp nhim (inheritance of acquired characters) do Lamarck xut v s
di truyn ha hp (blending inheritance), ngha l s pha ln "tinh cha
huyt m" con ci.
1. S ra i v pht trin ca di truyn Mendel
T u H Lan (Pisum sativum), vi tng v
phng php nghin cu c o, nm 1865 Gregor
Mendel (Hnh 1) pht hin ra cc quy lut di truyn
c s u tin v qua suy ra s tn ti tt yu ca cc
n v i truyn c th - nhn t di truyn (genetic
factor) - quy nh cc tnh trng c truyn t th h
ny sang th h khc m sau ny gi l gene. Tuy nhin,
gii khoa hc ng thi khng hiu v do khng
th nh gi tm vc v i ca pht minh ny.
Hnh 1 G. Mendel
Mi n nm 1900, ba nh thc vt hc l Carl
Correns (Germany), Hugo de Vries (Netherlands) v Erich von Tschermak
(Austria) c lp nhau khm ph li cc quy lut di truyn ca Mendel. V
di truyn hc chnh thc ra i t y m ngi sng lp l Mendel.
14
Trong nhng nm u th k XX, nh ng dng di truyn Mendel,

cc nh chn ging pht hin thm cc hin tng nh: tri khng hon
ton, ng tri, gene gy cht, a allele, cc kiu tng tc gene... giai
on ny, ngoi thuyt t bin ca H.de Vries nm 1901, cn c hai s
kin lin quan n s ra i ca thuyt di truyn nhim sc th v di
truyn hc qun th sau ny, l s khi xng "thuyt nhim sc th"
bi Walter Sutton v Theodor Bovary nm 1902 v vic thit lp quy lut
Hardy-Weinberg nm 1908.
Mt s thut ng thng dng cng c xut trong giai an ny,
nh: di truyn hc (genetics) bi W.Bateson nm 1906, gene, kiu gene
(genotype) v kiu hnh (phenotype) bi W.Johannsen nm 1909.
2. S ra i v pht trin ca thuyt di truyn nhim sc th
T 1910, Thomas Hunt Morgan (Hnh 2) cng vi
ba cng s l Alfred H.Sturtevant, Calvin Bridges v
Herman J. Muller xy dng thnh cng thuyt di
truyn nhim sc th (chromosome theory of inheritance)
da trn i tng nghin cu l rui gim Drosophila
melanogaster. Hc thuyt ny xc nhn rng gene l n
v c s ca tnh di truyn nm trn nhim sc th (
trong nhn); trn cc gene sp xp theo ng thng
Hnh 2 T.H.Morgan
to thnh nhm lin kt. Nhng ng gp ng k ca cc mn xut

sc ca Morgan l: xy dng bn di truyn (Sturtevant 1913), ch ra
c ch xc nh cc kiu hnh gii tnh rui gim (Bridges 1916) v pht
trin phng php gy t bin bng tia X (Muller 1927). Vi ng gp to
ln Morgan c trao gii Nobel nm 1933 v Muller nm 1946.
Nm 1931, Barbara McClintock (Hnh 3) v Harriet
Creighton thu c bng chng vt l trc tip v ti t
hp ng. Sau , hin tng ny cng c C. Stern
quan st Drosophila. Nh vy ti t hp c th c
pht hin c v mt vt l ln di truyn ng vt cng
nh thc vt. n 1944, McClintock pht hin cc yu
t di truyn vn ng (transposable genetic elements), v
b c trao gii Nobel nm 1983 v khm ph ny.
Hnh 3 B.McClintock
3. S ra i v pht trin ca di truyn hc phn t

S ra i ca di truyn hc phn t (molecular genetics) gn lin vi
cc khm ph v DNA (deoxyribonucleic acid) t gia th k XX trn i
15
tng nghin cu ch yu l cc vi sinh vt. Tuy nhin, trc Friedrich

Miescher (1869) khm ph ra mt hn hp trong nhn t bo gi l
nuclein m thnh phn chnh ca n sau ny c bit l DNA.
Hnh 4 Beadle, Tatum, Jacob v Monod (t tri sang)
V mi quan h gia gene v protein, t 1902 Archibald Garrod qua

nghin cu bnh alcaptonuria ngi gi rng y l mt tnh trng
ln Mendel, c th lin quan ti s sai hng mt enzyme. Bng cc th
nghim gy t bin cc gene lin quan n cc con ng sinh ha trn
nm mc Neurospora, nm 1941 George Beadle v E.L.Tatum (Hnh 4)
xc nhn mi gene kim sot s tng hp mt enzyme c th. Chnh gi
thuyt mt gene-mt enzyme (one gene-one enzyme hypothesis) ni ting
ny m ng cho s ra i ca di truyn ha-sinh, v hai ng c
trao gii Nobel cng vi Joshua Lederberg nm 1958. V sau, gi thuyt
ny c chnh xc ha l mt gene xc nh ch mt chui polypeptid cu trc s cp ca cc protein, trong c cc enzyme.
Vy bn cht ca gene l g? Nm 1944, Oswald
Avery (Hnh 5) v cc cng s l MacLeod v
McCarty bng th nghim bin np in vitro chng
minh rng DNA l vt cht mang thng tin di truyn.
Nm 1949, Erwin Chargaff cng b cc kt qu u
tin v thnh phn ha hc ca DNA mt s loi.
Hnh 5 O.T. Avery
Vic nghin cu cu trc phn t

DNA c bt u t 1951 vi cc
dn liu nhiu x tia X ca Rosalind
Franklin v Maurice Wilkins (Hnh
6). Cc s liu ha hc v vt l ny
l c s m t James Watson v
Francis Crick (Hnh 7) xy dng
thnh cng m hnh cu trc phn t
DNA nm 1953, cn gi l chui
Hnh 6 R.Franklin (tri) v M.Wilkins
16
xon kp (double helix). Pht minh v

i ny m ra k nguyn mi cho s
pht trin ca di truyn hc v sinh
hc ni chung. Vi pht minh ,
Watson v Crick cng vi Wilkins
c trao gii Nobel nm 1962 .
Bi bo nhan "Mt cu trc cho
Deoxyribose Nucleic Acid" ca
Watson v Crick ng trn tp ch
Nature ngy 25/4/1953 c nh gi
Hnh 7 J.D.Watson (tri) v F.H.C.Crick
l mt bi bo khng bnh thng. Ch vn vn c 128 dng nhng ng

sau bi bo l c mt bc tin lch s v i ca di truyn hc m mi
dng l mt cu chuyn. Tht vy, sau cu trc chui xon kp l hng
lot cc khm ph mi. Nm 1958 Matthew Meselson v Franklin Stahl
chng minh s ti bn bn bo ton ca DNA; v nm 1961
Seymour Benzer hon tt cng trnh
nghin cu cu trc tinh vi ca gene;
Francois Jacob v Jacques Monod
(Hnh 4) tm ra c ch iu ha sinh
tng hp protein (gii Nobel 1965 vi
Andre Lwoff); S.Brenner, Jacob v
Meselson khm ph ra RNA thng tin;
S.Brenner v F.Crick chng minh m
ditruyn l m b ba; cng trnh gii m
Hnh 8 H.G.Khorana (tri) v M.Nirenberg
di truyn ny c hon thnh vo thng 6 nm 1966 bi hai nhm nghin

cu ca Marshall Nirenberg v Har Gobind Khorana (gii Nobel nm
1968; Hnh 8).
4. S ra i v pht trin ca cng ngh DNA ti t hp
C th ni, nn tng ca cng ngh DNA ti t hp (recombinant
DNA technology) c thnh lp t 1972 khi Paul Berg (Hnh 10) to ra
phn t DNA ti t hp u tin trong ng nghim (recombinant DNA in
vitro). Mt nm sau Herbert Boyer v Stanley Cohen (Hnh 10) ln u
tin s dng plasmid to dng DNA. Lnh vc ng dng mi ny ca
sinh hc phn t to ra mt cuc cch mng mi trong sinh hc. ng
gp ng k trong lnh vc ny l khm ph v cc enzyme gii hn
(restriction enzyme) t 1961-1969 ca Werner Arber, Daniel Nathans v
17
Hamilton Smith (gii Nobel 1978; Hnh 10); xut cc phng php xc
nh trnh t base trong cc nucleic acid nm 1977 bi P.Berg, W.Gilbert
Hnh 9 Cc nh khoa hc ot gii Nobel y hc lin quan k thut gene.

T tri sang: D.Nathans, H.Smith, W.Arber, P.Sharp v R.Robert.
Hnh 10 Cc nh khoa hc ot gii Nobel ha hc lin quan k thut

gene. T tri sang: H.Boyer, S.Cohen, P.Berg, W.Gilbert, F.Sanger v
K.Mullis.
v Frederick Sanger (gii Nobel ha hc 1980; Hnh 10); s khm ph ra

cc gene phn on (split gene) nm 1977 bi Phillip Sharp v Richard
Robert (gii Nobel 1993; Hnh 9); s pht minh ra phng php PCR
(polymerase chain reaction) ca Kary B.Mullis nm 1985 (Hnh 10) v
phng php gy t bin nh hng (site-directed mutagenesis) ca
Michael Smith t 1978-1982 (gii Nobel ha hc 1993)...
Cng vi nhng thnh tu ng dng ly k trong sn xut v i sng
x hi, nh vic sn xut cc ch phm y-sinh hc bng cng ngh DNA
ti t hp, s dng liu php gene (gene therapy) trong iu tr bnh di
truyn, to cc ging sinh vt mi bng con ng bin i gene
(genetically modified organisms = GMOs), d n b gene ngi (Human
Genome Project = HGP)... gy ra khng t hoi nghi, tranh ci xung quanh
cc vn v o l sinh hc (bioethics) v an ton sinh hc (biosafety).
III. i tng v cc lnh vc nghin cu ca di truyn hc

Trong giai on u, i tng ca di truyn hc l cc thc vt, ng
vt, ngi v cc vi sinh vt. T dn ti s hnh thnh cc lnh vc
nghin cu tng ng l di truyn hc thc vt, ng vt, ngi v di
truyn hc vi sinh vt, trong di truyn hc t bo l c s. Giai on
18
ny ko di t thi Mendel cho n thp nin 1940, vi c trng l

nghin cu quy lut di truyn cc tnh trng qua cc th h. V vy n
thng c gi l giai on di truyn hc Mendel hay di truyn hc c
in (Mendelian or classical genetics).
T thp nin 1950 n nay, vi s ra i ca di truyn hc phn t
(molecular genetics), i tng nghin cu l t chc, cu trc, chc nng
v c ch hot ng ca cc b gene (genomes), cc gene v cc sn phm
ca chng mc phn t. c bit vi s ra i ca cc k thut to dng
gene (gene-cloning techniques) t thp nin 1970, vic nghin cu c bn
cng nh ng dng tr nn ht sc thun li. S phn ha thnh cc
chuyn ngnh lc ny l v cng phong ph v a dng, nh: di truyn
hc bnh (genetics of disease), di truyn hc ung th (genetics of cancer),
di truyn hc pht trin (developmental genetics), cng ngh sinh hc
(biotechnology)...Gn y cn xut hin mt s lnh vc nghin cu mi
nh genomics, DNA chip technology, DNA microarray technology...
Mt hng khc ca di truyn hc chuyn nghin cu cu trc di
truyn ca cc qun th v s bin i di truyn bn trong qun th v
gia cc qun th. l nhnh di truyn hc qun th (population
genetics), m nguyn l c s ca n c G.Hardy (England) v
W.Weinberg (Germany) c lp a ra nm 1908. Tuy nhin, lnh vc
nghin cu ny ch thc s bt u t thp nin 1930 vi cc cng trnh
ca R.A.Fisher, J.B.S.Haldane v Sewall Wright. Ngy nay cc nh di
truyn hc khng cn thin v nghin cu s bin i mc kiu hnh m
tp trung vo s bin i phn t trong mt qun th nhm tm hiu
ngha tin ha ca cc bin i . V nh th di truyn hc qun th tr
thnh nn tng cho cc thuyt tin ha hin i.
Qua phn tch trn cho thy ba nhnh chnh ca di truyn hc, l:
di truyn hc Mendel, di truyn hc phn t v di truyn hc qun th.
IV. Cc phng php nghin cu ca di truyn hc

Vic nghin cu di truyn hc c tin hnh bi nhiu phng php
khc nhau. Bn cnh cc phng php kinh in c th cn c s pht
trin v tch hp ca cc phng php t ton hc, tin hc, vt l v ha
hc c bit l trong lnh vc sinh hc phn t.
1. Cc phng php kinh in c th ca di truyn hc
Trc ht l phng php t th phn dng chn cc dng
thun lm b m trong cc php lai, cc phng php lai mt hoc ng
thi nhiu tnh trng gia cc b m do Mendel xut. Trong bao
gm c cc hnh thc lai thun nghch v lai phn tch (testcross) nhm rt
19
ra quy lut, kim tra kiu gene hoc dng thit lp bn di truyn.
i vi nghin cu di truyn ngi v mt s vt nui giao phi cn
huyt (consanguineous), c trng l phng php phn tch ph h
(pedigree analysis) nhm xc nh c im di truyn tri-ln ca mt tnh
trng hoc bnh tt; nghin cu tr sinh i cng trng v khc trng
nhm xc nh h s di truyn (heritability) ca tnh trng; phng php
gy t bin (mutagenesis) kt hp vi lai hu tnh dng trong nghin cu
v chn to ging, c bit l thc vt...
2. Phng php ton hc
Trong nghin cu khoa hc ni chung v di truyn hc ni ring, vic
p dng cc cng c ton thng k v l thuyt xc sut phn tch nh
lng v l gii cc kt qu nghin cu l rt thit yu. Chnh iu lm
cho di truyn hc tr thnh mt khoa hc chnh xc v mang tnh d bo.
iu ny th hin r trong cc cng trnh nghin cu ca Mendel, Morgan
cng nh trong cc nghin cu di truyn s lng v di truyn qun th.
3. Cc phng php vt l v ha hc
Trong nghin cu di truyn, c bit l di truyn phn t v t bo i
hi phi s dng cc k thut v phng php ca vt l v ha hc.
Chng hn, trong nghin cu hnh thi nhim sc th khng th thiu cc
loi knh hin vi quang hc v in t, cc k thut nhum bng (banding
techniques); nghin cu thnh phn ha hc v cu trc DNA i hi cc
phng php sc k v nhiu x tia X...
4. Cc phng php t bo hc
Trong nghin cu di truyn t bo c rt nhiu phng php c s
dng quan st hnh thi nhim sc th v thit lp kiu nhn
(karyotype) ca cc loi cng nh chn on cc bnh tt lin quan
n s bin i s lng v cu trc nhim sc th.
Bn cnh cc k thut nui cy m v chun b nhim sc th l cc
k thut nhum bng khc nhau, k thut lai hunh quang ti ch
(fluorescence in situ hybridization = FISH), k thut min dch t bo
hc... (xem Verma v Babu 1995).
5. Cc phng php ca sinh hc phn t - k thut di truyn
S tin b nhanh chng gn y ca sinh hc phn t v cng ngh
sinh hc l nh s pht trin mnh m ca cc k thut ti t hp DNA, lai
phn t, s dng cc mu d v phng php nh du khc nhau, phng
php PCR, cc phng php xc nh trnh t nucleic acid cng nh cc
phng php bin i vt liu di truyn mi.
Vi cc cng c k thut mi ny cho php i su nghin cu t
20
chc ca cc gene v b gene, cc c ch iu ha v bin i di truyn

mc phn t cng nh cc thnh tu ng dng mi trong y-sinh hc, nng
nghip v cc lnh vc khc ca i sng-x hi.
V. Cc nguyn tc nghin cu v phng php hc tp di truyn hc
1. Cc nguyn tc nghin cu ca di truyn hc
Trong nghin cu di truyn hc v sinh hc ni chung c cc nguyn
tc chung cn tun th nh l phng php lun, sau y: (1) Ly t bo
lm n v nghin cu; (2) Thng tin di truyn cha trong b gene t bo
chi phi mi biu hin sng ca n m cc gene l n v di truyn c s;
(3) S hot ng ca cc gene trong qa trnh pht trin c th l c trng
cho tng gene trong tng giai on c th; (4) Cc qu trnh trong cc h
thng sng phi c iu ha v kim sot m bo cho s tn ti ca
n l lin tc, trong ph bin l s t iu chnh bng cc c ch phn
hi thng tin (feed-back mechanism); (5) S thng nht gia cu trc v
chc nng biu hin tt c cc mc t chc khc nhau ca s sng;
(6) Tt c cc t chc v qu trnh sng u tun theo cc quy lut vt l
v ha hc; (7) S sng trn tri t tri qua qu trnh tin ha khong 3,5
t nm qua, v vy khi so snh, nhng nt tng ng gia chng cho thy
tnh thng nht v mt ngun gc v nhng nt d bit cho thy tnh pht
trin, s phn ha a dng tt yu ca chng.
2. Phng php hc tp mn di truyn hc
Cng nh bt k mn hc no khc, vic hc tp mn di truyn i
hi phi nm vng lch s mn hc, i tng, nhim v, phng php
nghin cu v h thng kin thc cn bn ca n. Bn cnh cc nguyn
tc ni trn vn rt cn cho t duy trong hc tp, di y nu mt s
im chnh lin quan phng php hc tp c th ca b mn.
(1) Nm vng cc kin thc lin mn (nh t bo hc, ha sinh hc, vi
sinh hc, hc thuyt tin ha...) v lin ngnh (nh cc khi nim v
nguyn l c bn ca ton thng k-xc sut, vt l v ha hu c).
(2) Nm vng h thng khi nim c bn cng nh cc thut ng mi
khng ngng ny sinh. Trong gene l khi nim cn bn c ni hm
khng ngng pht trin, c bit l trong ba thp nin li y.
(3) Hiu r bn cht ca cc nguyn l di truyn trong tng ch
cng nh mi lin quan gia chng c th gii thch v vn dng trong
gii quyt cc bi ton hoc tnh hung ca i sng v thc tin sn xut.
(4) nm kin thc v pht trin cc k nng t duy mt cch vng
chc i hi phi bit vn dng kin thc vo gii bi tp cng nh cc k
nng thc hnh th nghim.
21
(5) Di truyn hc l mt khoa hc thc nghim, nn thng tin thu

c l nh cc quan st t th gii t nhin, v phng php khoa hc
chnh l cng c hiu bit cc quan st . Ni n phng php
nghin cu khoa hc l ni n cc bc tin hnh theo mt trnh t t
chc cng vic cht ch sau y: Quan st Gi thuyt D on
Thc nghim ( kim tra gi thuyt t ra) xut gi thuyt mi.
Cng cn lu rng, c tnh ca khoa hc l hoi nghi, i hi phi
c bng chng xc thc, l kt hp gia logic v tr tng tng, l gii
thch v d on, khng c s c on; ngi nghin cu hay nh khoa
hc phi nhn bit sng t, trung thc, v t, v ni chung l chu s chi
phi ca cc nguyn tc o c c tha nhn rng ri.
(6) Trong khi hc gio trnh, bn nn lm t nht mt tiu lun v mt
vn cp nht mnh yu thch. iu rt l th v b ch. Bi cng
vic ny i hi s say m tm ti cc thng tin mi, c bit l trn mng
vit mt bi tng lun c tnh khoa hc v trnh by trong mt seminar.
(7) Bi di truyn hc l mt ngnh khoa hc non tr nhng pht trin
vi tc cc nhanh, nn khi lng kin thc mi tch ly c l v
cng phong ph v a dng. c th cp nht thng tin v mn hc i
hi phi tng cng kh nng s dng ting Anh v internet. iu quan
trng l phi to cho mnh mt hoi bo hc tp, mt kh nng v phng
php t hc v thnh lp cho c mt th mc tra cu. Trong ng k
l cc trang web (c gii thiu trong tng chng), hoc c th s dng
ngay cc t kha (key words) c cho tng ch tm kim vi
cng c c th ni mnh nht hin nay l Google.
VI. Di truyn hc vi cng ngh sinh hc, tin hc v cc vn x hi
Nh cp, s pht trin ht sc nhanh chng ca di truyn hc
trong vi thp nin qua, c bit l s tin b ca cng ngh sinh hc
(biotechnology) ni chung c nhng tc ng mnh m ln nhiu
ngnh khoa hc v trn mi mt ca i sng, kinh t, chnh tr v x hi
phm vi ton cu. Di truyn hc c hnh dung v tr trung tm v
giao thoa vi sinh hc, ha sinh hc, k ngh, y-dc, nng nghip, sinh
thi hc, kinh t hc, lut, x hi hc v trit hc.
Gio s danh d mn ha hc i hc Havard, F.H.Westheimer,
bnh lun v sinh hc phn t nh sau:"Cuc cch mng tr tu v i nht
ca 40 nm qua xy ra trong sinh hc. Liu c th tm ra mt ngi
no c hc ngy nay m khng hiu bit cht g v sinh hc phn t?"
(dn theo Weaver v Hedrick 1997, tr.15).
Cc thnh tu t c nh ng dng di truyn hc trong nng nghip
22
l v cng to ln, gp phn to nn cuc "cch mng xanh ln th hai" vi

s ra i ca hng lot cc ging vt nui-cy trng c u th lai vt tri,
cc sinh vt bin i gene (GMOs) mang nhng c tnh hon ton mi l.
Trong y hc, l s ra i ca hng lot cc dc phm c sn
xut bng k thut di truyn dng cho iu tr bnh v ci bin tr thng
minh ca con ngi; l cc phng php chn on v iu tr bnh
mc phn t...S thnh cng ca d n b gene ngi (HGP) vo thng 4
nm 2003 cho php chng ta ln u tin c c ton b trnh t
khong 3,2 t cp nucleotide trong b gene con ngi (Homo sapiens).
HGP l mt trong nhng k cng thm him v i nht trong lch s nhn
loi (NHGRI 2005). Theo c tnh mi nht c cng b ngy
21/10/2004 trn tp ch Nature, b gene chng ta cha s lng gene m
ha protein thp mt cch ng kinh ngc, khong 20.000 n 25.000 ch
khng phi l 50.000 n 140.000 gene nh d on ban u hoc 35.000
theo d on trong vi ba nm li y (NHGRI 2005).
Chnh s kt hp tin hc v my tnh trong nghin cu sinh hc phn
t dn ti s ra i mt ngnh mi l sinh-tin hc (bioinformatics) cho
php thu thp, t chc v phn tch s lng ln cc s liu sinh hc nh
s dng mng my tnh v cc ngun d liu (databases). V mt s lnh
vc nghin cu mi khc cng ra i nh: genomics - phn tch ton b
genome ca mt sinh vt c chn, DNA microchip technology - xc
nh cc t bin trong cc gene, DNA microarray technology - nghin
cu cch thc mt s lng ln cc gene tng tc ln nhau v c ch
mng li iu ha ca t bo kim sot ng thi s lng cc k ln
cc gene...
Nhng thch thc cho tng lai ca nghin cu khoa hc v cc b
gene (genomics) i vi sinh hc, vn sc khe v x hi cng c
t ra (Collins v cs 2003). S hon tt ca HGP t n khng c ngha l
xong m ng hn l im khi u cho cng cuc nghin cu thm
ch cn hng th hn. Cc nh nghin cu hin gi ang c gng lm sng
t mt s qu trnh phc tp nht ca sinh hc, l: mt a b pht
trin t mt t bo n l bng cch no, cc gene phi hp chc nng ca
cc m v c quan nh th no, s tin nh bnh tt xy ra nh th no v
b no ngi lm vic ra sao (NHGRI 2005).
Cng vi nhng thnh tu ng dng ly k trong sn xut v i sng
x hi ni trn, nhiu vn mi c t ra cho cc ngnh gio dc, lut,
trit hc, x hi hc v gy khng t hoi nghi, tranh ci xung quanh
cc vn v o l sinh hc, an ton sinh hc v mi sinh.
23
Ti liu Tham kho

Ting Vit
H Hunh Thy Dng. 1997. Sinh hc Phn t. NXB Gio Dc.
Phm Thnh H. 2000. Di truyn hc. Ti bn ln II, NXB Gio Dc.
Phan C Nhn (ch bin), Nguyn Minh Cng, ng Hu Lanh. 1999. Di
truyn hc. NXB Gio Dc.
Ting Anh
Collins FS, Green ED, Guttmacher AE, Guyer MS. 2003. A vision for the
future of genomics research. Nature, Vol. 422, No. 6934, p.835-847.
McKusick V. 1998. Mendelian Inheritance in Man. 12th ed., Johns
Hopkins University Press, Baltimore.
National Human Genome Research Institute (NHGRI)/ National Institute
of Health (NIH). 2005: http://www.genome.gov/
http://www.ncbi.nlm.nih.gov/
Online Mendelian Inheritance in Man (OMIMTM):
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
Tamarin RH. 1999. Principles of Genetics. 6th ed, McGraw-Hill, Inc, NY.
Verma RS and Babu A. 1995. Human chromosome : principles and
techniques. 2nd ed, international edition, McGraw-Hill, Inc., New York.
Watson JD and Crick FHC. 1953. A structure for Deoxyribose Nucleic
Acid. April 25,1953, Nature, Vol.171, page 737.
Weaver RF, Hedrick PW. 1997. Genetics. 3rd ed, McGraw-Hill
Companies, Inc. Wm.C.Brown Publishers, Dubuque, IA.
Zinnen T. 2005. JD Watson and FHC Crick - A structure for Deoxyribose
Nucleic Acid - Nature, 25 April 1953. (http://www.accessexcellence.org)
24
Chng 1
C s ca Di truyn hc Mendel
Cho n u th k XX, mi ngi cn cha hiu c c ch ca s
di truyn, mc d vn bit rng con ci sinh ra thng ging b m. Quan
nim ph bin cho n gia th k XIX c gi gn trong ci gi l
thuyt di truyn ha hp (theory of blending inheritance) nhm gii thch
s kin con ci mang cc c im ca c hai b m. Tuy nhin, n nm
1866 Gregor Mendel a ra thuyt di truyn gin on (theory of
particulate inheritance), vi gi rng: n v di truyn c th kim sot
mt tnh trng c truyn t th h ny sang th h khc tn ti di
dng ht, ngy nay ta gi l gene.
Cc khm ph quan trng ca Mendel t nn mng cho s ra i ca
di truyn hc sau ny. Nh Thomas Hunt Morgan nhn nh: "Trong
mi nm nghin cu cy u H Lan trong ngi vn ca tu vin, G.
Mendel lm nn s khm ph v i nht trong sinh hc t c
trong nm trm nm qua".
I. Tiu s Mendel - Cha ca Di truyn hc

Gregor Mendel sinh nm 1822, ln ln trang tri ca cha mnh ti
mt tnh ca Austria (o). V gia nh ngho
nn ng phi vo tu vin tip tc vic hc
ca mnh. Trong khong thi gian ny, Mendel
nghin cu vt l v ton l nhng mn hc
gip ng nhiu trong cc th nghim di truyn
sau ny. ng c gi ti i hc Vienna
thi ly bng gio vin chnh thc, nhng
khng v quay v tu vin "dy hc" trong
nhiu nm.
Hnh 1.1 Gregor Mendel trong ngi vn ca tu vin Brno.
Khi cn trang tri ca cha mnh, Mendel quan tm ti cc cy ci

v con vt, v thng gi li nhng ci hoa, con ong v chut. Sau ny
tu vin Brno ng tp trung vo cc cy u H Lan (Pisum sativum).
Mendel xc nh c cc nguyn l di truyn c s t cc th
nghim chn ging thc vt. Cc kt qu nghin cu ny c Mendel
trnh by nm 1865 trc Hi Nghin cu Khoa hc T nhin Brno v
cng b nm 1866 Germany trong mt bi bo nhan l Cc th
nghim lai thc vt (Experiments on Plant Hybrids). Bi bo ny nhanh
chng c mt nhiu th vin, nhng nhng ngi cng thi ng khng
25
hiu c cc pht hin ca ng, c l mt phn l do ng s dng ton

hc l gii cc kt qu ca mnh. Ngoi ra, hu ht cc nh nghin cu
ng thi do tin hnh nhiu tnh trng ng thi dn ti cc kt qu ri
bi nn khng th nhn ra c cc nguyn l di truyn c s.
Mendel tr thnh tu vin trng t nm 1868 v khng cng b thm
mt kt qu no v di truyn na k t sau kit tc nm 1866.
Mendel qua i nm 1884 trc khi cng trnh ca ng c gii
khoa hc thu hiu. Mi n nm 1900, cng trnh ca ng mi c ba
nh thc vt hc c lp nhau khm ph li, l Carl Correns ca
Germany, Hugo de Vries ca Netherlands v Erich von Tschermak ca
Austria. y l mc khi u cho cc nghin cu di truyn hc hin i.
Ngy nay, phng php th nghim ca Mendel c xem l th d kinh
in v s nghin cu khoa hc c lp k hoch cn thn v bi bo ca
ng l s minh ha tuyt vi ca mt thin ti khoa hc.
II. i tng v phng php th nghim ca Mendel

1. i tng
(a)
(b)
Hnh 1.2 (a) By tnh trng tng phn u H Lan c Mendel nghin
cu; dng tri nm bn tri ca mi trng hp. (b) Cu to hoa u,
phng php th phn cho v cy u H Lan.
26
Mendel chn u H Lan (Pisum sativum) lm i tng nghin cu

v chng c hai c im c bn l sai khc nhau v nhiu tnh trng tng
phn d quan st (hnh 1.2a) v sinh sn bng li t th phn. Ngoi ra,
u c hoa kh ln nn thao tc d dng (hnh 1.2b); c kh nng cho s
lng i con nhiu; v nhiu ging u lc by gi c gi tr kinh t cao.
2. Phng php
Tnh cht c o ca phng php nghin cu Mendel th hin
ch: (1) Chn cc dng thun (pure lines) khc nhau bng cch cho t th
phn lin tip nhiu th h dng lm dng b m trong cc php lai; (2)
Theo di trc tin kt qu di truyn ring bit ca tng tnh trng qua vi
th h, trong th h cy lai th nht hay F1 sinh ra do giao phn gia
hai dng b m thun chng khc nhau, cn th h cy lai th hai hay F2
sinh ra t s t th phn ca cc cy lai F1, ri sau mi tin hnh
nghin cu s di truyn ng thi ca hai hoc nhiu tnh trng; (3) Khi
qut v l gii cc kt qu th nghim thu c bng ton thng k v xc
sut; v (4) Kim tra li mt cch cn thn cc gi thuyt khoa hc bng
cc php lai thun nghch (reciprocal matings) v lai phn tch (testcross).
III. Lai mt tnh v nguyn l phn ly

1. Kt qu th nghim lai mt tnh (monohybrid cross)
Mendel tin hnh by php lai mt tnh khc nhau v cc kt qu
thu c c trnh by Bng 1.1.
Bng 1.1 Cc kt qu lai mt tnh ca Mendel
F2
TT
Kiu hnh P
F1
1 Ht trn
nhn
Trn
5474 trn : 1850 nhn
2 Ht vng xanh
Vng
6022 vng : 2001 xanh
3 Hoa ta trng
ta
705 ta : 224 trng
4 Qu phng tp
Phng
882 phng : 299 tp
5 Qu xanh vng
Xanh
428 xanh : 152 vng
6 Hoa dc thn nh Dc thn
651 dc thn : 207 nh
7 Thn cao thp
Cao
787 cao : 277 thp
T l F2
2,96:1
3,01:1
3,15:1
2,95:1
2,82:1
3,14:1
2,84:1
T tt c cc php lai trn cho thy: Khi b m th h xut pht (P)

thun chng khc nhau v mt cp tnh trng tng phn, th th h F1
tt c con lai u biu hin ch mt tnh trng ca b hoc m, tnh trng
c gi l tnh trng tri (dominant) v tnh trng kia khng quan st
c gi l tnh trng ln (recessive). Sau cho cc con lai F1 t th
phn th th h F2 ng thu c c hai kiu hnh (phenotype) ca b m
ban u vi t l xp x 3/4 tri v 1/4 ln.
Ngoi ra, Mendel cng cho cc cy F2 t th phn ring r v theo di
s phn ly th h F3. Kt qu cho thy 1/4 cy ca F2 sinh ra kiu hnh
27
ln tt c u l cc cy ln thun chng; iu c ngha l tt c con ci

ca chng l ln. Tuy nhin, trong s 3/4 biu hin kiu hnh tri th mt
s l tri thun chng, cn s khc th ging nh cc c th F1 ch
chng cho i con gm c tri v ln. Nhn chung, c ba kiu c th F2
l: 1/4 tri thun chng, 1/2 tri khng thun chng (cho i con vi t l
3 tri :1 ln) v 1/4 ln thun chng.
2. Gii thch v kim chng nguyn l phn ly
T cc kt qu th nghim Mendel kt lun rng, thng qua cc
giao t b m truyn cho con ci cc nhn t di truyn (genetic factor)
m ngy nay ta gi l gene. Mendel cn gi rng cc nhn t ny tn ti
di vi dng bin i (nay gi l cc allele) xc nh cc kiu hnh khc
nhau ca cng mt tnh trng. ng gi nh rng mi c th c hai allele
ca mi gene, mt ci nhn t giao t ca b v mt ci t giao t ca m.
Mc d iu i vi chng ta by gi c v n gin, nhng thi i
Mendel khng c ai hiu c n.
By gi ta hy xt th nghim 2. Trc tin, quy c cc gene xc nh
cc tnh trng tri v ln bng cc ch ci vit hoa v vit thng, chng
hn: A - ht vng, v a - ht xanh. Nh vy c ba kiu gene (genotype),
trong hai kiu ng hp t (homozygote) - c hai allele ging nhau:
AA v aa, tc dng thun chng v mt kiu d hp t (heterozygote) cha hai alele khc nhau: Aa, tc dng lai. V allele vng l tri hn allele
xanh, nn c th d hp t Aa c cng kiu hnh vi th ng hp tri AA.
P
Ht vng (AA) Ht xanh (aa)
Giao t P
A
a
F1
Aa (vng)
Giao t F1
( A : a)ci
( A : a)c
Khung Punnett
F2
AA
Aa
Aa
aa
T l kiu gene 1 AA : 2 Aa : 1 aa
T l kiu hnh 3 vng (A-) : 1 xanh (aa)
Hnh 1.3 S biu din kt qu lai mt tnh ca Mendel.
Trong gim phn, mi b m thun chng ht vng (AA) v ht xanh

(aa) ch cho mt loi giao t mang allele tng ng l A v a. Do kt
qu ca s th tinh ch to ra mt kiu d hp t Aa, ngha l tt c con lai
28
F1 u c kiu hnh tri ht vng. Khi bc vo gim phn, cc c th F1

d hp t (Aa) s cho hai loi giao t (A v a) vi t l tng ng.
cng l thc cht ca nguyn l phn ly (principle of segregation), hay quy
lut th nht ca Mendel (Mendel's first law). Kt qu ca s t th tinh
ngu nhin gia cc loi giao t c v ci ca F1 ny s cho ra bn kiu
t hp F2, vi t l phn ly theo kiu gene l 1AA: 2Aa: 1aa v t l
kiu hnh tng ng l 3 vng (A-): 1 xanh (aa). Lu rng thng thng
ngi ta s dng khung Punnett (Punnett square) do nh di truyn hc
ngi Anh R.C.Punnett a ra nm 1905 xc nh kt qu di truyn ca
cc php lai. S biu din kt qu lai mt tnh c nu hnh 1.3.
khng nh nguyn l phn ly, Mendel tin hnh hai th nghim:
Mt l, cho cc c th d hp t F1 t th phn nh ni trn; v hai l,
cho F1 lai ngc tr li vi b hoc m c kiu hnh ln. Php lai vi mt
c th ln nh th c gi l lai phn tch (testcross), thay v gi l lai
ngc (backcross) bi v n cho php kim tra kiu gene ca mt c th
tri l d hp hay ng hp. C s di truyn ca kiu lai ny nh sau:
B m
Aa (ht vng)
aa (ht xanh)
Giao t 50% A : 50% a
100% a
i con 50% Aa (vng)
: 50% aa (xanh)
3. Nguyn l phn ly v tnh ph bin ca n
Sau khi cc nguyn l di truyn ca Mendel c khm ph li nm
1900, tnh ph bin ca cc nguyn l Mendel ni chung v nguyn l
phn ly ni ring c cc nh nghin cu khng nh bng cch lp li
cc php lai ca ng (chng hn gia u ht vng v ht xanh; bng 1.2)
cng nh tin hnh cc php lai tng t cc ng vt v thc vt khc.
Bng 1.2 Cc kt qu lai lp li u H Lan
Nh nghin cu
Mendel (1866)
Correns (1900)
Tschermak (1900)
Bateson (1905)
Darbishire (1909)
Vng
6.022
1.394
3.580
11.902
109.060
Nhn
2.001
453
1.190
3.903
36.186
T l F2
3,01:1
3,08:1
3,01:1
3,05:1
3,01:1
Tnh ton b
131.958
43.733
3,02:1
Ni dung chnh ca nguyn l hay quy lut phn ly c th tm lc

nh sau: Cc allele l nhng dng khc nhau ca cng mt gene; trong
cc th d hp t chng phn ly v cc giao t vi t l tng ng.
IV. Lai hai tnh v nguyn l phn ly c lp

1. Kt qu th nghim lai hai tnh (dihybrid cross)
29
xc nh s di truyn ng thi ca nhiu cp tnh trng, Mendel

tin hnh nhiu th nghim khc nhau. Bng 1.3 gii thiu kt qu lai
hai tnh gia cc ging u thun chng ht vng-trn v ht xanh-nhn.
Bng 1.3 Cc kt qu lai hai tnh ca Mendel
Th h
Ptc
F1
F2
Kiu hnh ht
Vng-trn xanh-nhn
Vng-trn
Vng-trn
Vng-nhn
Xanh-trn
Xanh-nhn
Tng =
S lng
315
101
108
32
T l F2
(quan st)
9,84
3,16
3,38
1,0
T l F2
(k vng)
9
3
3
1
556
Vi php lai ny, tt c con lai F1 u c kiu hnh tri kp l ht vng

v trn. Khi cho F1 t th phn, F2 xut hin 4 kiu hnh l vng-trn,
vng-nhn, xanh-trn v xanh-nhn vi t l xp x 9:3:3:1.
2. Gii thch v ni dung nguyn l phn ly c lp
Nu xt t l phn ly ca tng tnh trng F2, ta c: 315 + 101 = 416
vng v 108 + 32 = 140 xanh, xp x 3 vng : 1 xanh. Tng t, v hnh
dng ht, ta c 315 + 108 = 423 trn v 101 + 32 = 133 nhn, xp x 3 trn
: 1 nhn. iu chng t mi tnh trng u tun theo quy lut phn ly 3
tri :1 ln.
Bng cch p dng quy tc nhn xc sut ca cc bin c c lp (xem
mc VI), ta d dng chng minh c rng s phn ly ca hai t l ny l
hon ton c lp nhau nh d on ban u. Tht vy, (3 vng :1 xanh)(3
trn :1nhn) = 9 vng-trn : 3 vng-nhn : 3 xanh-trn : 1 xanh-nhn.
Cn lu l t l 9:3:3:1 ny cng c Mendel tm thy trong khi lp
li th nghim vi cc tnh trng khc. T ng mi xy dng nn
nguyn l phn ly c lp (principle of independent assortment), cn gi
l quy lut th hai ca Mendel (Mendel's second law). Ni dung ca
nguyn l ny pht biu rng: Cc allele ca cc gene khc nhau th phn
ly mt cch c lp vi nhau trong qu trnh hnh thnh giao t (kt qu
l to ra t l 9:3:3:1 th h F2 t mt php lai hai tnh).
minh ha cho nhng iu trnh by trn y, ta quy c: A - vng,
a - xanh, B - trn, b - nhn.
Lu : kim tra li gi thuyt phn ly c lp, Mendel tin hnh
lai phn tch gia cc cy vng-trn F1 (AaBb) vi cy xanh-nhn (aabb).
Kt qu thu c gm 55 vng-trn : 49 vng-nhn : 51 xanh-trn : 53
30
xanh-nhn, tng ng vi t l 1:1:1:1 = (1:1)(1:1). iu chng t

cc cy F1 cho bn loi giao t vi t l ngang nhau, ngha l cha hai
cp gene d hp phn ly c lp.
vng, trn
xanh, nhn
Ptc Kiu hnh
Kiu gene
AABB
aabb
Giao t
AB
ab
F1 Kiu gene
AaBb
Kiu hnh
vng, trn
Giao t
AB : Ab : aB : ab
Khung Punnett
F2
AB
Ab
aB
ab
AB
AABB
AABb
AaBB
AaBb
Ab
AABb
AAbb
AaBB
Aabb
aB
AaBB
AaBb
aaBB
aaBb
ab
AaBb
Aabb
aaBb
aabb
T l kiu gene
1/16 AABB + 2/16 AaBB +
2/16 AABb + 4/16 AaBb
1/16 AAbb + 2/16 Aabb
1/16 aaBB + 2/16 aaBb
1/16 aabb
T l kiu hnh
= 9/16 vng, trn
= 3/16 vng, nhn
= 3/16 xanh, trn
= 1/16 xanh, nhn
Hnh 1.4 C s di truyn hc ca nguyn l phn ly c lp.
V. S di truyn Mendel ngi

Cng nh u H Lan, rui gim hay mo, ngi c rt nhiu tnh
trng di truyn theo cc quy lut Mendel. Chng hn, theo thng k ca
Victor A.McKusick nm 1994, c 6.678 tnh trng v cc bnh n gene.
Cho n ngy 8/2/2005, cc s liu v s lng gene v kiu hnh c
nu bng 1.4 (OMIM 2005).
Ni chung, vic xc nh phng thc di truyn ngi l tng i
kh khn, v mi gia nh c t con, thng khng qu 10 ngi. khc
phc iu ngi ta s dng phng php phn tch ph h (pedigree
analysis). Di y nu mt s tnh trng tri v ln ngi m khng
phn tch c im ca cc kiu di truyn (xem chng 11).
31
Bng 1.4 S lng cc mc
Gene c trnh t bit

Gene c trnh t v kiu hnh r
M t kiu hnh, c s ph.t r
Kiu hnh hay locus Mendel, c
s phn t cha bit
Cc kiu hnh chnh yu khc c
c s Mendel cn kh nghi
Tng
NST
thng
9517
360
1512
Lin
kt X
423
38
137
Lin
kt Y
48
0
2
DNA
ty th
37
0
27
Tng
10.025
398
1.678
1326
134
1.464
2150
14.865
153
885
2
56
0
64
2.305
15.870
1. Cc tnh trng ln (recessive traits)

ngi, hu ht cc ri lon di truyn l ln (xem bng 1.5). i a
s nhng ngi mc cc bnh ny thng c b m u bnh thng v
kiu hnh, nhng li mang gene bnh trng thi d hp.
Bng 1.5 Mt s ri lon n gene thuc nhim sc th thng ngi
(phng theo Campbell v Reece 2001; Lewis 2003)
Ri lon
Cc ri lon ln
Bch tng
Ha x nang
Galactosemia
Gaucher
Hemochromatosis
Phenylketonuria
Bnh hng cu lim
(ng hp t)
Bnh Tay-Sachs
Cc ri lon tri
Achondroplasia
Bnh Alzheimer
Bnh Huntington
Hypercholesterolemia
Khng dung np
lactose
Hi chng Marfan
Cc triu chng (v nguy c mc phi)

Thiu sc t da, tc v mt (1/22.000)
Tha cht nhy phi, dch tiu ha, gan
Tch ly galactose cc m; tr n; tn thng mt
v gan. (1/100.000; x l bng king galactose).
Gan v lch sng phng, thiu mu, xut huyt ni
C th gi li st; nguy c ly nhim cao, tn thng
gan, tim v ty , tha sc t da
Tch ly phenylalanyl trong mu; thiu sc t da bnh
thng; tr n, hn m, cht tui nh (1/10.000)
Tn thng lch v nhiu c quan; nguy c ly nhim
cao (1/500 ngi M gc chu Phi; ng tri)
Tch ly lipid trong cc t bo no gy suy thoi thn
kinh; m mu; cht thi th u
Ln vi t chi ngn, u v thn bnh thng
Thoi ha tm thn; thng xy ra mun mng
Thoi ha tm thn v cc c ng mt kim sot
Tha cholesterol trong mu; bnh tim; 1/500 l d hp
Khng c kh nng phn gii ng lactose, gy ra
tnh trng chut rt sau khi n loi ng ny
T chi di nh vn, ngc lm, hng thy tinh th,
cc ngn tay mnh khnh, ng mch ch suy yu
32
Bnh thn a nang

Tt nhiu ngn
Cc bng trong cc qu thn, ur trong mu, huyt p

cao, au bng di
Tha cc ngn tay, ngn chn
Hai bnh ln in hnh l bch tng v ha x nang. Nhng ngi

b bch tng (albino) l do thiu ht sc t melanin, nn da d trng bch,
tc v trng en ca mt tr nn nht khc thng (hnh 1.5)... Ha x
nang (cystic fibrosis) l mt bnh di truyn gy cht ph bin nht M
(USA). Bnh ln ny ph bin nht nhng ngi M da trng gc Capca
(Caucasians), vi tn s chung l 1/1.800, ngha l trung bnh c 25 ngi
c mt ngi mang allele ln ny (Campbell v Reece 2001) hay i vi
tr s sinh l 1/2.500 (Weaver v Hedrick 1997). Ngi b bnh ny c
c im l tit ra mt lng d tha cht nhy dy phi, ty v cc c
quan khc. Cc cht nhy ny c th lm nhiu lon s th, tiu ha v
chc nng ca gan v lm cho ngi bnh ri vo nguy c vim phi v
cc bnh truyn nhim khc. Nu khng c iu tr, hu ht tr em mc
bnh ny s b cht tui ln nm. Theo thng k ca McKusick nm
1994, c 1.730 mc cho cc locus ln.
2. Cc tnh trng tri (dominant traits)
Mc d hu ht cc allele c hi l allele ln, nhng mt s cc ri
lon ngi l do cc allele tri (xem bng 1.5). Trong s c mt vi
allele khng gy cht, chng hn nh tt tha cc ngn tay v chn (hnh
1.5), hoc c mng da gia cc ngn tay v chn. Cc tnh trng nh c
tn nhang, di tai thng cng nh cc kh nng un li hnh ng v gp
ngc li ln trn u do cc gene tri n khc nhau kim sot. Theo
thng k ca McKusick nm 1994, c 4.458 mc cho cc locus tri.
Hnh 1.5 Mt s v d v di truyn Mendel ngi.

T tri sang l bch tng, tt nhiu ngn v dng ln ph bin (achondroplasia).
33
Th d in hnh v ri lon tri nghim trng l dng ln ph bin

do thoi ha sn gi l achondroplasia (hnh 1.5), u v thn mnh pht
trin bnh thng nhng tay chn ngn mt cch bt thng; t l mc
bnh ny l khong 1 trn 25.000 ngi. Ch nhng ngi d hp t mi
b ri lon ny; cn kiu gen ng hp t tri gy cht phi. Trng hp
khc l bnh Huntington (Huntington's disease), mt dng ri lon do s
suy thoi ca h thn kinh thng xy ra t sau tui trung nin. Khi
bnh tin trin, n lm cho cc c ng trn mi phn ca c th mt kh
nng kim sot. S mt mt cc t bo no dn ti mt tr nh v kh nng
suy xt, gp phn y nhanh s suy thoi. Cui cng, mt lun cc k
nng vn ng lm cho khng nut v ni nng c. Ci cht thng xy
ra sau khi cc triu chng bt u biu hin khong 10-20 nm
(Campbell v Reece 2001).
VI. L thuyt xc sut trong d on v phn tch di truyn hc

hiu r cc pht hin ca Mendel v cc nguyn l ca di truyn
hc ni chung, cng nh vn dng cc kin thc ny mt cch c hiu
qu vo trong hc tp v thc tin i sng-sn xut, chng ta cn nm
vng mt vi khi nim v nguyn l xc sut c bn sau y.
1. Mt s khi nim v tnh cht c bn ca xc sut
(1) Mt cch n gin, xc sut (probability) c nh ngha bng s
ln xy ra mt bin c hay s kin (event) c th chia cho tng s c may
m bin c c th xy ra. Nu ta k hiu xc sut ca bin c A l
P(A), m l s ln xut hin ca A v n l tng s php th hay ton b s
kh nng c th c, khi : P(A) = m / n; trong 0 m n, v n > 0.
Nh vy, 0 P(A) 1.
(2) Php th l vic thc hin mt nhm cc iu kin xc nh, v d
mt th nghim tung ng xu hay gieo ht xc xc hoc mt php lai c
th. Cc kt cc khc nhau c th c t php th gi l cc bin c, c
k hiu bng cc ch ci in hoa A, B, C...V d: Khi tung mt ng xu, s
kin xy ra ch c th l mt sp (S) hoc nga (N) vi xc sut tng
ng l 0,5. Tng t, kiu gene d hp Aa c th to ra hai loi giao t
mang A v a vi xc sut ngang nhau l 0,5 trong khi cc kiu gene ng
hp nh aa chng hn ch cho mt loi giao t mang a; v vy i con ca
php lai phn tch Aa aa c t l k vng l 0,5 Aa : 0,5 aa.
Khi thc hin php th c th xut hin mt trong cc loi bin c sau:
-Bin c ngu nhin (A) l s kin c th xy ra nhng cng c th
khng, 0 P(A) 1.
-Bin c chc chn ( ) l s kin nht thit xy ra, P() = 1.
34
-Bin c khng th c () l s kin nht thit khng xy ra, P() = 0.

-Bin c xung khc: Hai bin c A v B gi l i xung khc vi nhau
nu tch ca chng l mt bin c khng th c: AB = P(AB) = 0
v P(AB) = P(A) + P(B).
-Bin c i lp: "khng A" () c gi l bin c i lp ca bin
c A khi = \ A v A= . Khi P() = 1 P(A).
-Nhm y cc bin c hay khng gian bin c s cp () l tp
hp ton b cc bin c s cp () ca mt php th m khi c thc
hin th nht thit mt trong chng phi xy ra, v c hin tng xung
khc tng i. V d, dy cc bin c B1, B2,..., Bn lp thnh mt nhm
y nu tho mn hai iu kin: (i) Tng ca chng l mt bin c chc
chn: B1 B2 ... Bn = ; v (ii) Chng xung khc tng i mt: BiBj
= ; ij (i, j = 1,2,...,n).
2. Mt s nguyn l xc sut c bn
2.1. Quy tc cng
Quy tc cng pht biu rng: xc sut kt hp ca hai (hoc nhiu) s
kin xung khc tng i xy ra l tng cc xc sut ring r ca chng.
(i) Vi A, B l hai bin c bt k, ta c P(AB) = P(A) + P(B) P(AB)
(ii) Nu A v B l hai bin c xung khc, th: P(AB) = P(A) + P(B)
(iii) H qu: Nu l bin c i lp ca A, th P() = 1 P(A).
V d, vi kiu gene Rr, nu ta k hiu xc sut ca loi giao t mang
allele R l P(R) v ca loi giao t mang allele a l P(r), theo l thuyt ta
c: P(R hoc r) = P(R) + P(r) = 1/2 + 1/2 = 1.
2.2. Xc sut iu kin
nh ngha: Nu A, B l hai bin c bt k v P(A) > 0, th xc sut
iu kin ca bin c B vi iu kin bin c A xy ra l:
P(B/A) = P(AB) : P(A).
V d: T kt qu th nghim lai gia hai th u thun chng ht vng
v ht xanh ca Mendel, hy tm xc sut mt cy u ht vng F2 l
th d hp (Vv). Bng lp lun thng thng ta thy trong s bn kiu t
hp F2 c 3 kiu t hp cho kiu hnh ht vng (V-) nhng ch c 2 kiu
l d hp (Vv). V vy xc sut cn tm l 2/3.
Nu gii theo nh ngha xc sut, ta k hiu: A l s kin ht vng
F2 v B l s kin ht vng d hp. Theo l thuyt, F2 c 4 s kin ng
kh nng vi t l l 1VV: 2Vv: 1vv. y P(A) = 3/4 v P(A.B) = P(B)
= 2/4 P(B/A) = P(AB) : P(A) = 2/4 : 3/4 = 2/3.
B
35
2.3. Quy tc nhn

T nh ngha v xc sut iu kin, ta i n nh ngha v hai bin
c c lp nh sau: Hai bin c A v B c gi l c lp vi nhau nu
P(B/A) = P(B) hoc P(A/B) = P(A). Ngha l s xy ra hay khng xy ra
ca bin c ny khng nh hng n s xy ra ca bin c kia.
Khi , quy tc nhn c pht biu nh sau: Xc sut trng hp ca
c hai bin c c lp bng tch cc xc sut ring r ca chng. Ngha
l, nu A v B l cc bin c c lp th: P(AB) = P(A).P(B)
V d: Khi gieo mt ng xu hai ln lin tip hoc gieo hai ng xu
cn i v ng cht cng mt lt th c 4 kh nng xy ra l (SS), (SN),
(NS), (NN) vi xc sut ngang nhau. Tht vy, xc sut xut hin c hai
mt sp hoc nga l: P(S,S) = P(N,N) = 1/2 1/2 = 1/4; cn xc sut xut
hin mt mt sp v mt mt nga l P(S,N) = 2 1/2 1/2 = 1/2; v tng
cc xc sut ca tt c cc s kin ng nhin bng 1.
T y ta c th xy dng c s ca "php th c lp", nguyn tc
gii bi ton lai hai tnh v cc phng php biu din kt qu lai nh sau:
(i) Mnh "php th c lp" di y c thit lp da trn quy
tc nhn xc sut, ch yu dng kim tra xem quy lut di truyn chi
phi ng thi c hai tnh trng no trong mt php lai l c lp hay
lin kt (nu l lin kt th lin kt hon ton hay khng hon ton), hoc
mt tnh trng no c lin kt vi gii tnh hay khng. Mnh ny
c pht biu nh sau: Nu cc gene phn ly c lp v t hp t do, th
t l phn ly ng thi ca c hai tnh trng bng tch cc t l phn ly
ring r ca cc tnh trng , v ngc li.
V d 1: Kt qu ca mt php lai hai tnh c t l phn ly l 3:3:1:1 v
cc t l ca tng tnh l 3:1 v 1:1. Ta ni rng cc tnh trng tun
theo quy lut phn ly c lp, v: 3:3:1:1 = (3:1)(1:1).
V d 2: Kt qu s t th tinh ca mt c th F1(hoc tp giao gia
cc c th F1 sinh ra t cc b m thun chng khc nhau v tng cp gene
allele) v mt tnh trng no m c t l phn ly l 9:3:3:1 hoc l mt
bin dng ca cng thc phn ly . Ta c th khng nh rng tnh trng
ny tun theo quy lut tng tc gia cc gene khng allele phn ly c
lp. Tht vy, t kt qu trn cho thy i lai c 9+3+3+1 = 16 kiu t
hp vi t l ngang nhau, chng t (cc) c th F1 cho t nht 4 loi
giao t vi t l tng ng, ngha l d hp t nht 2 cp gene phn ly
c lp. Ngha l tnh trng tun theo quy lut tng tc gene.
(ii) H qu: Nu tch cc t l phn ly ring r ca cc tnh trng khc
vi t l phn ly ng thi ca c hai tnh, chng t cc tnh trng tun
36
theo quy lut di truyn lin kt.

V d: Kt qu ca mt php lai cho thy t l phn ly ca c hai tnh
l 1A-bb:2A-B-:1aabb hoc 3A-B-:1aabb, trong khi t l phn ly ca mi
tnh trng vn l 3:1.Ta d dng thy rng tch (3:1)(3:1) 1:2:1 hoc 3:1,
chng t cc tnh trng ny tun theo quy lut lin kt hon ton, v kiu
gene ca b m chng i vi trng hp u l Ab/aB Ab/aB hoc
AB/ab Ab/aB, v trng hp sau l AB/ab AB/ab.
(iii) Nguyn tc tng qut gii mt bi ton lai hai hoc nhiu tnh
T nhng iu trnh by trn y cho thy rng thc ra ton lai gm
hai dng tng qut: lai mt tnh v lai nhiu tnh, v vic gii mt bi ton
lai hai tnh tr ln ni chung c thc hin theo ba bc chnh: Bc 1:
Tch xt quy lut di truyn ca tng tnh trng; Bc 2: Gp xt quy lut
di truyn ca hai tnh hoc tng hai tnh trng mt ( xc nh xem chng
tun theo quy lut no, c lp hay lin kt); v Bc 3: Thit lp (cc) s
lai kim chng (xem "Php gii ton lai", Hoa hc tr s 362 tr.40-41).
Nh vy, ci kh ca cc bi ton lai thc ra l dng lai mt tnh, v
ci kh nht ca dng ton ny l xc nh cho c quy lut chi phi tnh
trng v cc kiu quan h c th c gia cc gene allele cng nh gia cc
gene khng allele vi nhau. T mi c th xc nh cc kiu gene, kiu
hnh, v cui cng l kim chng cc kt qu bng s lai thch hp.
(iv) Cc phng php biu din kt qu lai: Bi v bt c mt mnh
quy lut no cng l "mnh ko theo" v c tnh xc sut (ngha l cha
ng kh nng tin on tim tng), cho nn vic tnh ton v biu din
cc kt qu k vng ca bt k mt php lai no r rng l u da trn c
s xc sut m ch yu l quy tc nhn. C nhiu cch khc nhau trong
biu din kt qu ca cc php lai. Chng hn, trnh by di dng khung
Punnett, vn l phng php kinh in ca di truyn hc. Mt phng
php thng dng khc l phng php phn nhnh (forked-line approach),
Phng php ny c th dng tm xc sut ca cc kiu i con i vi
nhiu gene phn ly c lp; n cng rt tin dng khi xc nh thnh phn
allele v xc sut ca cc loi giao t t mt kiu gene c th. Ngoi ra,
tu trng hp c th s dng trc tip quy tc nhn (product rule).
2.4. Cng thc xc sut nh thc
n gin, ta xt php th ng xu gm hai s kin i lp l mt
sp (S) v mt nga (N), vi cc xc sut tng ng l p v q, trong q =
1-p. Gi s trong n php th c lp c tin hnh, s kin S xut hin k
ln v s kin N l n-k. tnh cc xc sut ny ta phi s dng cng thc
xc sut nh thc (binomial probability) sau y:
37
Pn(k) = Ckn .pk.qn-k ; k = 0, 1, 2,..., n.

trong , Ckn l h s nh thc; y Ckn = n!/ k!(n-k)!
Lu : Dy n php th ny cn gi l dy php th Bernoulli, v n
tho mn ba iu kin: (1) N l dy c lp; (2) Trong mi php th,
khng gian bin c s cp ch c hai bin c s cp i lp l S v N; v
(3) Xc sut ca mt bin c S hoc N l khng thay i trong mi php
th, P(S) = p v P(N) = q = 1 p.
V d: Gieo mt ng xu lin tip ba ln, c th xy ra 23 = 8 kh nng
c lp v th t trong 4 nhm sau y:
3 mt sp
2 sp v 1 nga
1 sp v 2 nga
3 mt nga
SSS
SSN
SNN
NNN
SNS
NSN
NSS
NNS
Vi gi thit p = q =1/2, da vo cng thc xc sut nh thc ta d

dng tnh c xc sut ca mi trng hp trn nh sau:
P(3 mt sp)
= 1(1/2)3(1/2)0 = 1/8
P(3 mt nga) = 1(1/2)0(1/2)3 = 1/8
P(2 sp 1 nga) = 3(1/2)2(1/2)1 = 3/8
P(1 sp 2 nga) = 3(1/2)1(1/2)2 = 3/8
2.5. Cng thc xc sut ton phn
Gi s dy B1,B2,...,Bn l mt nhm y cc bin c, ngha l chng
c hp l mt s kin tt yu (B1B2...Bn = ) v gm tng i xung
khc (BiBj = , vi i j; i,j = 1, 2,...,n); v gi A l mt bin c bt k.
Khi :
A = A = (B1B2...Bn ) A = (B1 A) (B2 A) ... (Bn A)
p dng cc nh l cng v nhn, ta c cng thc xc sut ton phn
P(A) = P(B1).P(A/B1) + P(B2).P(A/B2) +...+ P(Bn).P(A/Bn)
= P(Bi).P(A/Bi) ; vi i = 1,..,n.
2.6. Cng thc Bayes
Vi gi thit nh trn cng thm mt iu kin mi l php th c
tin hnh v kt qu l s kin A xy ra. V cc Bi (i= 1, 2,...,n) lp
thnh mt nhm y nn cng vi A phi c ch mt s kin Bk no
xy ra. Vy khi A xut hin th s kin no trong s cc Bi c nhiu kh
nng xy ra hn c? Gii p cu hi ny c ngha l cn tnh xc sut
B
38
P(Bk/A). Vn dng nh l nhn xc sut, ta c:

P(ABk) = P(A).P(Bk/A) = P(Bk).P(A/Bk)
Suy ra: P(Bk/A) = P(Bk).P(A/Bk) : P(A) ; vi P(A) > 0.
Thay P(A) t cng thc xc sut ton phn trn, ta c cng thc
Bayes nh sau: P(Bk/A) = P(Bk).P(A/Bk) : P(Bi).P(A/ Bi)
Trong cc P(Bi) c gi l cc xc sut tin nghim (v chng
c xc nh trc khi tin hnh php th), cn P(Bk/A) c gi l xc
sut hu nghim (v n ch c xc nh sau khi tin hnh php th).
Cn lu rng, cc quy lut Mendel v thc cht l cc nh lut nhn
xc sut, cho nn tin on cc nguy c di truyn cn s dng n cng
thc Bayes, tc l nh l xc sut ca nguyn nhn. V bi ton t ra ch
c th gii quyt trn vn mt khi bit c cc xc sut tin nghim.
B
V d: Ly ngu nhin mt cy u ht vng F2 (trong th nghim ca

Mendel) cho lai vi cy ht xanh, v th h lai nhn c tt c l 6 cy
ht vng. Hy tm xc sut ca cy ht vng F2 em lai l th ng hp.
(Quy c: Y- ht vng, y - ht xanh).
Gii: Ta bit rng F2 c t l kiu gene l 1/4 YY : 1/2 Yy : 1/4 yy
v t l kiu hnh l 3/4 vng : 1/4 xanh. V cy ht vng (Y-) c chn
ngu nhin trong s cc cy ht vng F2 nn n c th l ng hp (YY)
hoc d hp (Yy), vi xc sut tng ng l 1/3 hoc 2/3.
Gi B1 - s kin "cy ht vng F2 ly ra l th ng hp"
B2 - s kin "cy ht vng F2 ly ra l th d hp"; (B1B2 = )
v A l s kin "6 cy ht vng nhn c th h lai".
Ta c cc xc sut tin nghim: P(B1) = 1/3 v P(B2) = 2/3
V cc xc sut iu kin: P(A/ B1) = 1 v P(A/ B2) = (1/2)6 = 1/64
Vy xc sut (hu nghim) cn tm l:
P(B1/A) = P(B1).P(A/ B1) : [P(B1).P(A/ B1) + P(B2).P(A/ B2)]
= (1/31) : [(1/31) + (2/31/64)] = 32/33 = 0,97.
B
Lu : Kt qu ny cho thy rng cy ht vng F2 (c ly ngu

nhin lai phn tch) c kiu gene ng hp l hu nh chc chn (n
97%), vi mc = 0,05. Ni cch khc, ch vi 6 cy ht vng thi
cng khng nh s ng tnh ca i con. n y hn l chng ta
thy r cng thc Bayes c tm quan trng nh th no trong vic tin
on nguyn nhn v nguy c di truyn, cng nh cho php l gii mt s
tnh hung phc tp (xem Hong Trng Phn 1995, 2000b).
39
VII. Phng php Khi-bnh phng (Chi-square method) trong

nh gi ph hp gia cc s liu quan st v k vng
Ni chung, cc s liu thng k thu c t cc th nghim vn sai
khc t nhiu so vi cc con s mang tnh cht l thuyt, tu thuc ch yu
vo mu th nghim v phng php ly mu. Trong trng hp , chng
ta bn khon khng r liu s gi nh "xp x" ca chng ta c tht chc
chn khng? Hay ni theo ngn ng thng k, "gi thuyt tng ng H0
c chp nhn hay b bc b", ngha l kt qu thu c c tht nghim
ng vi t l ca mt quy lut no hay khng?
c c cu tr li rt ro cho vn ny ch c cch l s dng
trc nghim Khi-bnh phng (2-test). y l mt cng c ton thng k
thng dng cho php kim tra ph hp gia cc tr s thc t quan st
c (observed, k hiu: O) v cc tr s l thuyt c k vng
(expected, k hiu: E) ca mt gi thuyt hay phn phi thc nghim khoa
hc no , hoc kim tra tnh c lp ca hai i lng ngu nhin.
Nh ta c th rt ra quy lut, hoc hiu qu ca hai phng php th
nghim no . ng v phng din thc hnh, phng php ny c
tin hnh n gin nh sau:
Bc 1: t gi thuyt tng ng H0 v sau tnh tr s 2 thc t
da theo cng thc: 2 = [(Oi Ei)2/ Ei ] ; i= 1, 2,...,n.
Bc 2: Tm tr s 2 l thuyt bng cch tra Bng cc gi tr ca
phn phi 2 vi k bc t do. Thng thng ngi ta s dng mc xc
sut sai lm P hay mc ngha = 0,05 v k = n 1; trong n l s lp
kiu hnh v n cn tu trng hp c th. Mc = 0,05 thng c
dng lm ranh gii phn chia gia min n nh chp nhn gi thuyt H0
v min n nh bc b gi thuyt H0. tin li, di y nu ra mt vi
tr s 2 = 0,05 l thuyt thng dng ng vi mt s bc t do k nh sau:
S bc t do (k)
2
Gi tr
= 0,05
3,84
5,99
3
7,82
4
9,49
Bc 3: So snh cc gi tr 2 thc t v l thuyt.

- Nu nh tr s 2 thc t nh hn tr s 2 l thuyt, tc l c mc
xc sut P hay > 0,05, gi thuyt H0 c chp nhn. Ngha l kt qu
thu c ph hp vi t l c gi nh.
- Ngc li, nu nh tr s 2 thc t ln hn hoc bng tr s 2 l
thuyt, tc l c mc xc sut P hay 0,05, gi thuyt H0 b bc b.
Ngha l kt qu thu c khng ph hp vi t l c gi nh.
40
V d: Trong th nghim lai mt tnh ca Mendel, F2 thu c 705

hoa tm v 224 hoa trng. Trn nguyn tc, vi hai kiu hnh F2 khin ta
c th ngh ti mt s t l l thuyt gn vi n nh 2:1, 3:1 hoc 9:7.
Nhng y t l "tm : trng" thc t l 3,15:1 nn t l k vng hp l
hn c l 3:1. chnh l gi thuyt H0 cn kim tra.
By gi ta c th tnh ton gi tr 2 thc t nh sau:
Kiu hnh
S quan st (Oi)
S k vng (Ei)
(Oi Ei)2/ Ei
Hoa tm
705
3/4 929 = 696,75
0,098
Hoa trng
224
1/4 929 = 232,25
0,293
Tng
929
929
2 = 0,391
Bng cch tra bng cc gi tr ca phn phi 2 = 0,05 vi k = 21= 1

bc t do, ta tm c tr s 2 l thuyt l 3,84. V tr s 2 thc t (0,391)
nh hn tr s 2 l thuyt (3,84) rt nhiu, nn gi thuyt H0 hon ton
c chp nhn. Ngha l kt qu th nghim trn ph hp mt cch st sao
vi t l 3:1. iu c ngha rng s sai khc gia cc s liu thc v
cc con s l thuyt tng ng l rt khng ng k, khng c ngha v
phng din thng k.
Cu hi v Bi tp
1. i tng v phng php th nghim ca Mendel c nhng c
im c o no m t Mendel khm ph ra cc quy lut di truyn
c s u tin, t nn mng cho s ra i ca di truyn hc?
2. Khi lai gia chut en v chut nu nhn c F1 ton chut en.
Sau cho cc chut ny tp giao vi nhau thu c F2 gm 53 en v 17
nu. Hy gii thch kt qu, vit cc s lai v tnh xc sut ca mi
trng hp phn ly kiu hnh c th c F2 (bit rng s chut F2 thu
c t mi t hp lai ca cc chut F1 trung bnh l bn con).
3. T kt qu lai cu sau y, hy xc nh kiu gene ca mi c th.
Php lai
i con
Trng-1 x trng-2
6 trng : 1 en
Trng-1 x trng-3
5 trng
Trng-1 x en-1
3 trng : 3 en
4. Cho mt rui gim mt nu cnh di giao phi vi mt rui gim
mt cnh di. i con thu c gm 51 di, 53 nu di, 17 ngn
v 18 nu ngn. Hy xc nh kiu gene ca cc rui gim b m.
41
5. Da vo cc php lai v kt qa di y, hy bin lun ch ra

cc quy lut di truyn v kiu gene ca cc b m trong mi php lai.
i con
Php lai
Vng, trn vng, trn
Vng, nhn vng, nhn
Xanh, trn vng, nhn
Vng,
trn
45
0
31
Vng,
nhn
Xanh,
trn
Xanh,
nhn
15
42
29
16
0
32
5
15
30
6. Gi s thc hin php lai gia con mo lng ngn, tha, c m

trng (llddSs) v mo lng di, rm, c m trng (LlDdSs). Hy trnh by
cc phng php nhn xc sut n gin v s phn nhnh tnh t l
k vng ca mi mt mo con c kiu hnh sau: lng ngn, tha, khng c
m trng; lng ngn, rm, c m trng; v lng di, rm, c m trng.
7. rui gim, mt (se+) l tri so vi mt mu nu ti (se; vit tt
ca sepia). Cho hai rui gim mt d hp lai vi nhau, v ly mt con
mt i con cho lai tr li vi mt b m mt . C may i con
php lai ngc xut hin rui gim mt mu nu ti l bao nhiu?
8. khng nh cc nguyn l di truyn ca Mendel, cc nh nghin
cu lp li cc th nghim u H Lan. Ring cc th nghim v mu
sc ht, F2 Correns thu dc 1.394 vng v 453 xanh, trong khi
Tschermak quan st thy c 3.580 vng v 1.190 xanh. Cc tr s ny c
ph hp vi nguyn l phn ly khng? Bn hy chng minh iu bng
cng c ton thng k thch hp.
9. Gi s ngi chng b bch tng, ngi v v cc con ca h (mt
trai v hai gi) u bnh thng. Khi ln ln, chng lp gia nh vi nhng
ngi cng khng mc bnh ny v mi gia nh ny u c mt trai v
mt gi bnh thng. Gi s xy ra s kt hn ng huyt gia hai a
chu c quan h cu c rut, khi xc sut sinh ra mt trai u lng
mc bnh ny l bao nhiu? Hy v s ph h ni trn v gii thch.
10. Gi s bn c mt cy u H Lan thn cao cha r kiu gene. Bn
em cy ny lai phn tch vi cy thn thp hoc cho n t th phn v
thu c tt c by cy u c thn cao. Hi xc sut cy thn cao em
lai kim tra c kiu gene ng hp l bao nhiu?
Ti liu Tham kho

Ting Vit
Nguyn Ngc King 1996. Thng k hc trong Nghin cu Khoa hc.
42
NXB Gio Dc, H Ni.

Phm Vn Kiu 1998. L thuyt Xc sut v Thng k Ton hc. NXB
Khoa hc v K thut, H Ni.
Hong Trng Phn 1995. nh gi hin tng ng tnh trong lai phn
tch nh cng thc Bayes. Thng tin Khoa hc v Gio dc s 11/1995, tr.
133-138, Trng HSP Hu.
Hong Trng Phn 2000a. Php gii ton lai. Hoa hc tr s 362, tr.40-41.
Hong Trng Phn 2000b. Cng thc Bayes v php tnh gn ng trong
phn tch di truyn hc. Thng bo Khoa hc s 4/2000, tr. 65-76, Trng
HSP H Ni.
Ting Anh
Brooker RJ. 1999. Genetics - Analysis and Principles. Benjamin/
Cummings Publishing Company, Inc., Menlo Park, CA.
Campbell NA, Reece JB. 2001. Essential Biology. Benjamin/Cummings,
an imprint of Addison Wesley Longman, Inc, San Francisco, CA.
Hartl DL, Freifelder D, Snyder LA. 1988. Basic Genetics. Jones and
Bartlett Publishers, Inc, Boston - Portola Valley.
Lewis R. 2003. Human Genetics: Concepts and Applications. 5th ed,
McGraw-Hill, Inc, NY.
<http://www.ncbi.nlm.nih.gov/Omim/mimstats.html>
Russell PJ. 2000. Fundamentals of Genetics. 2nd ed, Benjamin/ Cummings
Publishing Company, Inc, Menlo Park, CA.
Suzuki DT, Griffiths AJF, Miller JH, Lewontin RC. 1989. An Introduction
to Genetic Analysis. 4th ed, W-H Freeman and Company, New York.
Weaver RF and Hedrick PW. 1997. Genetics. 3rd ed, McGraw-Hill
Companies, Inc. Wm.C.Brown Publishers, Dubuque, IA.
Mt s trang web
http://www.mhhe..com/lewisgenetics5
htttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
http://fpt.netspace.org/MendelWeb/Mendel.htm
http://www.nord-rdb.com/~orphan
43
Chng 2
M rng v p dng
ca Di truyn hc Mendel
Nt c sc ca cc th nghim Mendel l s nht qun hon ton
gia cc quan st v gi thuyt ca ng. Tuy nhin, k t sau khi cc cng
trnh ca Mendel c khm ph li, ngi ta cn pht hin ra nhiu ngoi
l suy rng t m hnh Mendel. Trong chng ny, chng ta s tm hiu
cc vn sau: (i) S khc nhau gia cc kiu tri hon ton, tri khng
hon ton v ng tri; (ii) Tc ng ca gene gy cht; (iii) Hin tng
a allele; (iv) Tnh a hiu ca gene; (v) Cc kiu di truyn do nhiu gene
cng tc ng ln mt tnh trng - tng tc gene; (vi) C s di truyn ca
cc tnh trng s lng. Cc kiu di truyn lin kt v lin kt vi gii tnh
tuy cng c xem nh l s m rng ca cc nguyn l Mendel, nhng
s c trnh by trong mt chng ring, chng 4.
I. Cc kiu quan h gia cc gene allele i vi mt tnh trng

1. Cc kiu tri hon ton, khng hon ton v ng tri
K t sau nm 1900, ngi ta cn pht hin thm mt s trng hp
tri khc nhau, b sung cho t l 3 tri :1 ln ca Mendel.
1.1. Tri hon ton (complete dominance)
y l trng hp di truyn tri-ln Mendel. Trong hu ht cc trng
hp, allele bnh thng (hay kiu di) tri hon ton so vi cc allele t
bin. iu ny c th l gii da trn c s di truyn sinh ha ch, allele
tri cho sn phm protein hot ng chc nng bnh thng trong khi
allele t bin khng to ra c sn phm c hot tnh. Do cc c th
ng hp v allele ln khng hon thnh c con ng chuyn ha c
lin quan n gene ny. ngi, l trng hp ca cc allele t bin
ln gy bch tng, bnh phenylxtn-niu (phenylketonuria = PKU)...
Tuy nhin, mt s trng hp, allele t bin tri hn kiu di;
ngha l allele kiu di l ln. V d: ngi, kiu ln ph bin do khng
to c sn l tri, cho nn cc th d hp biu hin kiu hnh t bin.
1.2. Tri khng hon ton (incomplete dominance)
Khi lai gia hai ging hoa bn gi (four-o'clock; Mirabilis jalapa)
thun chng c hoa mu v hoa mu trng, Carl Correns thu c tt
c cc cy F1 c hoa mu hng, kiu hnh trung gian gia hai b m. Sau
khi cho cc cy F1 t th phn, t l kiu hnh F2 l 1 : 2 hng : 1
trng. Mc d t l kiu hnh ny c hi lch so vi ca Mendel, nhng
44
thc t n tng ng vi t l kiu gene 1:2:1 (hnh 2.1). Nu s dng quy

c gene A- l tri khng han ton so vi a- trng, ta c s lai sau:
Ptc
Hoa (AA) Hoa trng (aa)
Aa (Hoa hng)
F1
F2
T l kiu gene
AA : Aa : aa
T l kiu hnh
: hng : trng
tri ng hp t
d hp t
ln ng hp t
Hnh 2.1 S di truyn trung gian i vi mu sc hoa nhiu thc vt.
Bi kiu hnh ca th d hp l trung gian gia hai th ng hp, v

vy ta c th l gii trn phng din sinh ha rng hm lng sn phm
tch ly do mt allele tri kim sot l khng th hin kiu hnh mu
nh trong trng hp c mt c hai allelele tri.
1.3. ng tri (codominance)
ng tri l hin tng c hai allele khc nhau trong mt th d hp
cng biu hin ra cc sn phm c hot tnh khc nhau trong t bo. Cc
allele nh th c gi l cc allele ng tri. in hnh l trng hp
nhm mu AB ca h nhm mu ABO (hnh 2.2; xem gii thch mc 3
bn di) v nhm mu MN ca h nhm mu M-N ngi.
Hnh 2.2 Kiu hnh cc nhm mu A, AB v B. ( y cho thy s ng

tri nhm mu AB. Nhm mu O khng c khng nguyn no).
H nhm mu M-N (do mt locus thuc nhim sc th thng kim

sot) c hai allele LM v LN. Nh th, trong mt qun th s c ba kiu
gene LMLM, LMLN v LNLN (c th vit gn l MM, MN v NN) tng
ng vi ba kiu hnh hay nhm mu l M, MN v N. Nu cho rng cc
php hn phi thun nghch l tng ng, th c th c su kiu hn
phi vi cc t l kiu gene k vng i con c cho bng 2.1.
45
Bng 2.1 Cc t l k vng i con i vi h nhm mu M-N

B m
i con
M M
L L
LMLN
LNLN
LMLM LMLM
1
M M
M N
L L L L
M M
N N
L L L L
M N
M N
L L L L
M N
N N
L L L L
N N
N N
L L L L
1
Mt v d khc l allele ln gy bnh hng cu hnh lim. nhng
ngi d hp t v allele ny (HbAHbS), c hai allele u c biu hin
v cc t bo mu ca h cha c hemoglobin bnh thng v bt thng.
2. Tc ng ca gene gy cht (lethal)
Cc allele gy cht l nhng t bin c th tri hoc ln lm gim sc
sng hoc gy cht i vi cc c th mang n v do , lm bin i t l
3:1 ca Mendel. Nhiu gene c cc allele nh hng ln t l cht ch
khng gy cht; cc allele ny c gi l cc allele c hi (deleterious).
Hnh 2.3 Bin i mu lng chut.
Hnh 2.4 Mo Manx khng ui.
Ni chung, cc allele gy cht thng l ln v gy cht cc th ng

hp. V d, t bin bch tng thc vt lm cho cy cht giai on non
v khng c dip lc quang hp. Bnh thiu mu hng cu hnh lim
ngi (xem mc II) c th gy cht vi t l ng k tui trng thnh
khi allele t bin ln ny trng thi ng hp.
Tuy nhin, mt s allele gy cht l nhng t bin tri. in hnh l
th nghim lai v mu sc lng chut ca Lucien Cunot nm 1904. Khi
lai gia hai chut thn vng (allele vng l tri; Hnh 2.3), ng thu c t
l xp x 2 vng : 1 kiu di. Mt khc, khi lai gia cc chut vng vi
chut kiu di (mu agouti), ng thy rng i con c t l xp x 1:1.
46
Cunot kt lun rng tt c cc chut vng u l nhng th d hp, cn

cc th ng hp v allele vng u b cht giai on phi.
B m
Yy (vng)
Yy (vng)
YY : Yy : yy
i con
(cht)
2 vng : 1 agouti
Hin tng "khng ui" mo Manx (c pht hin u tin o

Manx nm 1935; Hnh 2.4) l mt tnh trng khc gy ra bi mt allele t
bin tri M; n c hiu qu tri cc th d hp v gy cht cc th
ng hp. V vy khi lai gia cc mo Manx (Mm Mm) bao gi cng
thu c mo Manx khng ui v c ui bnh thng.
3. Hin tng a allele (multiple allelelism)
Trn thc t, mi mt gene khng ch c hai allele m c th c nhiu
hn hai allele, gi l a allele. Cc allele l nhng trng thi cu trc khc
nhau ca cng mt gene pht sinh do t bin (xem chng 8).
Ni chung, nu mt gene trn nhim sc th thng (autosome) c n
allele khc nhau, th trong qun th c th c n(n+1)/2 kiu gene, trong
c n kiu ng hp v n(n 1)/2 kiu d hp (xem bng 2.2). y chnh l
c s ca hin tng a hnh (polymorphism) quan st c trong cc
qun th t nhin.
Bng 2.2 Mi quan h s lng gia cc allele v cc kiu gene
S allele
1
2
3
4
...
n
S th ng hp
1
2
3
4
...
n
S th d hp
0
1
3
6
...
Tng s kiu gene

1
3
6
10
...
n(n 1)/2
n(n+1)/2
V d: S di truyn h nhm mu ABO ngi c kim sot bi

mt gen autosome c ba allele chnh l IA, IB v IO; trong IO l ln, cn
cc allele IA v IB l ng tri. Trong mt qun th, ni chung c su kiu
gen tng ng vi bn kiu hnh hay nhm mu sau y:
Kiu hnh
A
B
AB
O
A A A O
B B B O
A B
O O
Kiu gene
I I ,I I
I I , I
I I
I I
By gi ta hy tm hiu c s di truyn min dch ca h nhm mu
ABO ny. S khc nhau gia cc nhm mu l do s c mt ca cc loi
khng nguyn v khng th . Cc khng nguyn (antigen) y l nhng
phn t kt hp protein-ng bm trn b mt ca cc t bo hng cu v
47
chng xc nh tn nhm mu tng ng. Cc c th mang allele IA

v/hoc allele IB c khng nguyn tng ng A v/hoc B; cn allele IO
khng to c bt k khng nguyn no (nn nhng ngi ng hp v
allele ln ny c kiu hnh O, ngha l "khng" c khng nguyn A hoc B
no c trn b mt cc t bo hng cu).
Cc khng th (antibody) l nhng protein do h thng min dch to
ra vi mt s lng ln nhm p ng vi cc khng nguyn c th t
bn ngoi. C th, trong huyt thanh nhng ngi mang nhm mu O
thy c c hai loi khng th khng-A v khng-B gi l v ; nhng
ngi nhm mu AB khng c bt k loi khng th no; cn nhng
ngi nhm mu A v B ch c mt loi khng th tng ng l v .
ngha lm sng ca nguyn tc truyn mu l ch khi truyn sai
nhm mu s xy ra phn ng ngng kt cht ngi do phn ng gia
khng nguyn b mt ca hng cu ngi cho (donor), m lng huyt
thanh l khng ng k, vi khng th c trong huyt thanh ca ngi
nhn (recipient). V th, nhng ngi c cng nhm mu th c th cho v
nhn ca nhau. c bit, nhm mu O do thiu c hai loi khng nguyn
A v B nn c th truyn cho mt ngi mang bt k nhm mu no;
ngc li ngi mang nhm mu AB c th nhn bt k nhm mu no.
Hin tng a allele tn ti ph bin trong cc qun th sinh vt khc
nhau. V d, gene kim sot mu mt -trng rui gim gm mt chui
12 allele, vi tnh tri gim dn t kiu di cho n trng t bin ln
(w) theo th t t tri sang phi v trn xung nh sau:
Allele
Mu
Allele
Mu
W+
di
We
eossin
Wsat
satsuma
Wbl
blood
Wco
coral
Wap
apricot
Ww
wine
Wi
ivory
Wap3
apricot3
Wt
tinged
Wch
cherry
w
white
Mt s gene ngi, chng hn nh cc gene i vi khng nguyn

bch cu ngi HLA (human leukocyte antigen) xc nh cc khng
nguyn trn b mt ca hu nh tt c cc t bo c th c nhiu allele. V
d, gene HLA-B c nhiu hn 30 allele c xc nh khc nhau v mt
khng nguyn trong mt s qun th. Kt qu ca s a dng ny l, trong
mt qun th c rt nhiu kiu gene gene HLA-B (465 kiu gene khc
nhau, vi 30 kiu ng hp v 435 kiu d hp), thc s to nn mt dy
bin d kiu gene rng.
II. Tnh a hiu ca gene (pleiotropy)

Hin tng mt gene nh hng n hai hoc nhiu tnh trng c
gi l tnh a hiu (pleiotropy). V d, trong cc th nghim u H Lan,
48
Mendel lu rng gene kim sot mu hoa tm v trng cng nh

hng ln mu sc ht (v xm hoc nu) v gy ra s c mt hoc khng
c mt ca cc vt mu tm b l. Trong v d allele kim sot lng vng
chut ni trn, ta thy rng n cn nh hng ln sc sng cc th d
hp v gy cht cc th ng hp.
Nhiu bnh di truyn ngi gy ra bi cc gen c tc dng a hiu.
Chng hn, bnh phenylxtn-niu (phenylketonuria = PKU) xy ra cc
c th ng hp v allele ln . Nhng ngi mc bnh ny thiu hn
enzyme cn thit cho s chuyn ha bnh thng ca amino acid
phenylalanine thnh sn phm sinh ha k tip. Khi so snh cc c th
bnh thng v PKU vi nhau cho thy mc phenylalanine nhm bnh
cao hn nhiu. Ngoi ra, nhng ngi bnh cn c mt s bin i khc
nh: ch s IQ thp hn, u b hn, v tc hi nht hn. Tt c cc hiu
qu a hiu ny c th hiu nh l hu qu ca s ri lon sinh ha c s.
Chng hn, cc bnh nhn PKU c s tch ly mt c t trong u
khin cho b no b tn thng v dn ti IQ thp hn, u b hn.
Mt v d khc v tnh a hiu ngi l bnh
hng cu hnh lim (sickle-cell disease). Vy tnh a
hiu gii thch trng hp ny nh th no? Nhng
ngi ng hp v allele t bin ln ny (HbSHbS)
ch to ra cc phn t hemoglobin bt thng, khin
cho tt c cc t bo hng cu c dng hnh lim,
kch thc b, mu nht (Hnh 2.5). Cc t bo
hnh lim nhanh chng b c th ph hy v gy ra
s thiu mu v suy yu c th ni chung. Ngoi ra,
Hnh 2.5 Cc t bo hng cu bnh thng (trn) v dng
hnh lim (di), vi phng i gn gp i ca hnh trn.
do hnh dng gc cnh m cc t bo hnh lim khng th vn chuyn trn

tru trong mu v c xu hng tch t v gy tc nghn cc mao mch.
Dng mu i n cc b phn c th b gim bt, gy st nh k, au
n, v tn thng cc c quan khc nhau nh no b, lch, tim, thn...
III. Cc kiu tng tc gia cc gene khng allele

K t sau khi pht hin li cc nguyn l di truyn ca Mendel,
xut hin nhiu cng trnh nghin cu trn cc i tng khc nhau, nh:
b ng, u ngt, la m, ng, rui gim, g, chut, ch, nga...Mt s kt
qu thu c t cc th nghim lai mt tnh cho thy t l phn ly khc
vi cc t l 3:1 hoc 9:3:3:1. Cc trng hp cho t l phn ly 9:3:3:1
49
hoc mt dng bin i ca n c l gii l do s tng tc qua li gia

cc gene khng allele phn ly c lp.
Tu trung c hai kiu tng tc gene, l: tng tc gia cc gen
allele ( xt trn) v tng tc gia cc gen khng allele (thng c
gi tt l tng tc gene). Do cc gene khng allele c th nm trn cng
mt cp nhim sc th hoc trn cc cp nhim sc th tng ng khc
nhau, cho nn v nguyn tc s c hai dng tng tc gene khng allele
tng ng l tng tc c lp v tng tc lin kt; v dng sau phi l
ch yu bi v s lng gene ca mt sinh vt nhiu hn s lng nhim
sc th ca n rt nhiu. Tuy nhin, trn thc t, khi ni n s tng tc
gia cc gene khng allele l ta mun ni ti s tng tc gia cc gene
khng allele phn ly c lp.
Lu : (1) S lng cc tnh trng hnh thnh nn mt c th sinh vt
ni chung l nhiu hn s lng gene m ha protein c mt trong b
gene ca n. Chng hn, theo c tnh gn y cho thy trong b gene
ngi c khong 25.000 gene khc nhau trong khi c ti 50.000 loi
protein thc hin tt c mi hot ng sng ca cc t bo. (2) Nh th, s
biu hin ca a s tnh trng l kt qu ca s tng tc gia nhiu gene
khc nhau trong qu trnh pht trin c th; v thc cht ca s tng tc
l do s tng tc gia cc sn phm hot ng ca cc gen c bn
cht protein hoc gia cc sn phm sinh ra t s xc tc ca cc enzyme.
(3) Con ng chuyn ha mt cht c th trong t bo l mt chui gm
nhiu phn ng sinh ha ni tip nhau m mi khu phn ng c xc
tc bi mt enzyme (chng 7). Ngay c mt enzyme hay protein c cu
trc bc bn cng gm mt s chui polypepetide thuc cc gene khc
nhau to nn (chng 6). (4) cho n gin, thng thng ta gii thch
cc kt qu tng tc bng hai gene nhng trn thc t, c th c nhiu
hn hai gene cng quy nh mt tnh trng.
Di y chng ta xt ba kiu tng tc gen chnh: Tng tc b tr,
tng tc t ch v tng tc a phn cng gp. Cc v d nu ra di y
l nhng th nghim kinh in ca di truyn hc. hiu c bn cht di
truyn ca cc tnh trng , c bit l cc tnh trng mu sc, chng ta
c gng lm sng t c ch sinh ha ca chng trong kh nng c th.
1. Tng tc b tr (complementary)
Tng tc b tr l trng hp tng tc gene lm xut hin kiu hnh
mi khi c mt ng thi cc gene khng allele trong mt kiu gene. Cc
gene b tr c th l gene tri hoc gene ln ( trng thi ng hp).
Tng tc kiu b tr biu hin di nhiu dng vi cc t l kiu hnh F2
khc nhau, nh 9:3:3:1; 9:6:1; 9:7.
50
1.1. Tng tc b tr vi t l 9:3:3:1

V d kinh in cho trng hp ny l cc th nghim ca W.Bateson
v R.C.Punnett v s di truyn hnh dng mo g. Khi lai gia cc ging
g thun chng mo hnh hoa hng vi mo n (cn gi l mo hnh l)
thu c F1 ton mo hoa hng, v sau khi cho tp giao F1 th F2 c t l
phn ly 3 mo hoa hng : 1mo n. Tng t, khi lai gia cc ging g
thun chng mo hnh ht u vi mo n, F1 gm tt c mo ht u v
F2 phn ly 3 mo ht u : 1 mo n. Nhng khi lai gia hai ging g
thun chng mo hoa hng v mo ht u, th F1 li thu c tt c c
mo hnh qu c ch (hay ht h o) v t l phn ly F2 xp x 9 qu c
ch : 3 hnh hoa hng : 3 hnh ht u : 1 mo n (hnh 2.6).
Gii thch: Cc kt qu trong hai th nghim u cho
thy cc dng mo hoa hng v ht u l tri so vi
dng mo n. Kt qu sau cng cho thy F2 c 16 kiu
t hp vi t l ngang nhau, trong khi F1 ng nht kiu
gen (v b m thun chng); iu chng t F1 cho
4 loi giao t vi t l tng ng, ngha l d hp t
v hai cp gene phn ly c lp. Suy ra tnh trng ny do
hai gene khc nhau chi phi, ngha l tun theo quy lut
tng tc gene. Mt khc, kiu hnh mi biu hin F1
v khong 9/16 F2 (ng vi s c mt ca c hai gene
tri khng allele) phi l kt qu ca s tng tc gia
cc gene tri khng allele theo kiu b tr.
Quy c: Da vo t l phn ly kiu hnh F2 trong
trng hp hai gene phn ly c lp v tn gi cc dng
mo theo ting Anh (rose: hoa hng, pea: ht u), ta c
c ch: R-P-
hoa hng: R-pp
ht u: rrP-
mo n: rrpp
Hnh 2.6 Cc kiu mo c trng ca cc ging g khc

nhau v cc kiu gene tng ng.
th quy c v kim chng n gin nh sau:

R-P-: mo hnh qu c ch (do b tr gia cc gene tri R v P)
R-pp: mo hnh hoa hng (do biu hin ca gene tri R)
rrP-: mo hnh ht u (do biu hin ca gene tri P)
rrpp: mo n (do khuyt c hai gene tri; kiu di)
Kim chng:
Ptc
mo hoa hng (RRpp) mo ht u (rrPP)
F1
mo qu c ch (RrPp)
51
F1F1 = RrPp RrPp = (Rr Rr)(Pp Pp)

F2 = (3R-:1rr)(3P-:1pp) = 9 R-P-: 3 R-pp : 3 rrP- : 1 rrpp
= 9 c ch: 3 hoa hng : 3 ht u : 1 n
Mt v d khc, l lai gia hai ging chut lng mu en vi mu
v qu (cinnamon) c F1 ton chut lng mu xm (c dng "mui tiu"
khi nhn gn, cn gi l agouti) v F2 cho t l 9 xm : 3 mu v qu : 3
en : 1 nu. Bn c th gii thch c s di truyn ca trng hp ny?
1.2. Tng tc b tr vi t l 9:7
V d: Th nghim ca Bateson v Punnett v s di truyn mu sc hoa
cy u ngt (Lathyrus odoratus). T php lai gia hai ging hoa trng
thun chng khc nhau, hai ng thu c F1 gm tt c cy lai c hoa mu
ta (purple). Khi cho cc cy F1 t th phn F2 nhn c 382 hoa
ta v 269 hoa trng; kt qu ny gn vi t l 9:7.
Gii thch: Vi cch lp lun nh trn, ta d dng thy rng kiu hnh
hoa ta l kt qu ca s tng tc b tr gia hai gene tri khng allele
phn ly c lp. Trc khi i vo gii thch c s di truyn sinh ha ca
cc kiu hnh, ta hy quy c v kim chng kt qu th nghim trn.
Quy c:
C-P- : hoa ta (do tc ng b tr gia cc gene tri C v P)
C-pp, ccP-, ccpp : hoa trng (do khng c mt y c hai gene tri)
Kim chng:
Ptc
ging hoa trng 1(CCpp) ging hoa trng 2 (ccPP)
F1
hoa ta (CcPp)
F1F1 = CcPp CcPp = (Cc Cc)(Pp Pp)
F2 = (3C-:1cc)(3P-:1pp) = 9 C-P- : (3 C-pp + 3 ccP- + 1 ccpp)
= 9 ta : 7 trng
By gi ta th gii thch c s sinh ha ca cc kiu hnh. S hnh
thnh mu hoa cy u ngt l kt qu ca s tng hp mt hp cht gi
l anthocyanin; n xy ra thng qua mt chui cc khu chuyn ha c
xc tc bi cc enzyme vn l sn phm ca cc gene. Nu nh bt k
khu no trong qu trnh tng hp ny b gin on do vng mt ca mt
enzyme hot ng th s hnh thnh mu sc khng xy ra. Mc d chi tit
chnh xc ca s tng hp mu sc cy u ngt cn cha r, nhng c
th minh ha bng m hnh tng qut hnh 2.7.
52
Kiu gene c cha C

Kiu gene c cha P
Enzyme (C)
Enzyme (P)
Cht tin thn Sn phm trung gian Anthocyanin

Hnh 2.7 S minh ha mi quan h gia cc gene tri C v P trong qu
trnh hnh thnh sc t anthocyanin cy u ngt.
i vi cc kiu gene c cha c hai gene tri C v P (C-P-), c y

cc enzyme cn thit cho vic to ra anthocyanin v do vy hoa c mu
ta. Trong khi , kiu gene cha cc (ccP- hay ccpp), enzyme th nht
khng c to ra hay khng c hot tnh; hu qu l, phn ng to sn
phm trung gian khng thc hin c. Tng t, kiu gene cha pp (Cpp hoc ccpp) th phn ng th hai bin i cht trung gian thnh
anthocyanin b dng li, v thiu hn mt enzyme tng ng. Ni cch
khc, nu nh kiu gen c mang cp allele hoc l cc hoc l pp th con
ng tng hp b gin on v cc sc t khng c to ra, v kt qu l
hoa mu trng.
1.2. Tng tc b tr vi t l 9:6:1
V d: S di truyn hnh dng qu b ng. Khi lai hai ging b ng
thun chng qu trn khc ngun gc vi nhau, F1 xut hin ton dng
qu dt, v F2 c s phn ly kiu hnh xp x 9 dt : 6 trn : 1 di.
Gii thch: Kt qu ny c th c gii thch theo mt trong hai cch
sau: b tr gia cc gene tri hoc b tr gia cc gene ln. n gin,
di y ta gii thch theo cch u, da trn quy c sau y:
Quy c: D-F- : qu dt (do tng tc b tr gia cc gene D v F)
D-ff v ddF- : qu trn (ch c mt trong hai gene tri D, F)
ddff : qu di (do khuyt ng thi c hai gene tri)
Kim chng:
qu trn-1 (DDff) qu trn-2 (ddFF)
Ptc
F1
qu dt (DdFf)
F1F1 = DdFf DdFf = (Dd Dd)(Ff Ff)
F2 = (3D-:1dd)(3F-:1ff) = 9 D-F-: (3 D-ff + 3 ddF-) : 1 ddff
= 9 qu dt : 6 qu trn : 1 qu di
2. Tng tc t ch (epistasis)
Tng tc t ch l hin tng mt gene ny km hm s biu hin ca
mt gene khc khng allele vi n. Gene t ch c th l tri hoc ln.
53
2.1. t ch do gene ln vi t l 9:3:4

V d: S di truyn mu sc lng chut (hnh 2.8). Khi lai gia hai
dng chut thun chng lng nu v bch tng, F1 xut hin ton chut
lng en; v khi cho cc chut F1 tp giao vi nhau th F2 c s phn ly
gn vi t l 9 en : 3 nu : 4 bch tng. gii thch kt qu ny, ta da
vo bin lun nh v d u tin (mc III-1.1) v quy c sau y:
Quy c: B-C- : en; bbC- : nu; B-cc v bbcc : bch tng
Gii thch: T quy c ny, ta thy rng allele c khi trng thi ng
hp (cc) c ch s biu hin ca B- v bb khin cho cc kiu B-cc v bbcc
khng c sc t (bch tng, albino). i vi hai kiu hnh cn li c th
gii thch theo mt trong hai cch sau: (1) Allele C l t bin tri, nn
mt kh nng t ch v bn thn n khng to mu; khi allele tri B
quy nh mu en l tri so vi allele b quy nh mu nu khi n trng
thi ng hp; kt qu l B-C- c kiu hnh lng en v bbC- cho kiu
hnh lng nu. Nh th y khng xy ra s tng tc b tr gia cc
gene tri B v C. Cch l gii ny r rng l hp l. (2) Allele C quy nh
mu nu v B l gene to mu, trong khi bb khng c kh nng . Do
khi gene tri C (khng c kh nng t ch) ng ring s cho mu nu;
cn ng chung vi gene tri B s cho hiu qu b tr tri vi kiu hnh
mu en. R rng cch gii thch ny ch hp l trn hnh thc khi cho
rng allele tri C xc nh mu nu.
Hnh 2.8 T tri sang l cc chut agouti en, agouti nu v bch tng.
Kim chng:
Ptc
Chut nu (bbCC) Chut bch tng (BBcc)
F1
Tt c chut en (BbCc)
F1F1 = BbCc BbCc = (Bb Bb)(Cc Cc)
F2 = (3B-:1bb)(3C-:1cc) = 9 B-C-: 3 bbC- : (3 B-cc + 1 bbcc)
= 9 en : 3 nu : 4 bch tng
2.2. t ch do gene tri vi t l 12:3:1
V d: S di truyn mu sc lng nga. Khi lai gia hai ging nga
54
thun chng lng xm v hung vi nhau, F1 thu c ton nga lng

xm. Sau khi cho tp giao cc nga F1 th F2 c t l kiu hnh xp x 12
xm : 3 en : 1 hung .
Gii thch: gii thch kt qu ny, ta quy c: A-B- v A-bb : xm;
aaB-: en; v aabb: hung . Theo , allele tri B quy nh mu en l
tri so vi b- hung . V s d A-B- v A-bb cho kiu hnh lng xm
trong khi chng c cha B v bb, bi v gene tri A t ch cc gene khng
allele v ng thi n cn c kh nng to mu xm, cn allele a khng c
c hai kh nng . iu ny c th hin qua s lai sau y:
Ptc
Nga xm (AABB) Nga hung (aabb)
F1
Tt c nga xm (AaBb)
F1F1 = AaBb AaBb = (Aa Aa)(Bb Bb)
F2 = (3A-: 1aa)(3B-:1bb) = (9 A-B- + 3 A-bb) : 3 aaB- : 1 aabb
= 12 xm : 3 en : 1 hung
2.3. t ch do gene tri vi t l 13:3
V d: S di truyn mu sc lng g. Khi lai gia ging g thun
chng, g Leghorn trng vi g Wyandotte trng, F1 thu c ton g
lng trng. Sau khi cho tp giao cc c th F1, F2 c t l phn ly kiu
hnh xp x 13 lng trng (white): 3 lng c mu (colored).
Gii thch: gii thch kt qu ny, ta quy c: I-C- , I-cc v iicc :
trng; v iiC-: c mu. Theo , allele tri C - gene sn xut cht to mu
(chromogen) l tri so vi allele c- khng c kh nng to mu; v allele
tri I (inhibitor) t ch gene khng allele vi n v n cng khng c kh
nng to mu, cn allele i khng c kh nng t ch ln to mu.
S lai:
Ptc
G Leghorn trng ( IICC ) G Wyandotte trng (iicc)
F1
Tt c g trng (IiCc)
F1F1 = IiCc IiCc = (Ii Ii)(Cc Cc)
F2 = (3I-:1ii)(3C-:1cc) = (9 I-C- + 3 I-cc + 1 iicc) : 3 iiC= 13 trng : 3 c mu
3. Tng tc cng gp - s di truyn a gene v cc tnh trng s lng
3.1. Tng tc cng gp (additive)
Tng tc cng gp hay s di truyn a gene (polygenic) l hin
tng di truyn c trng ca mt s tnh trng s lng (quantitative
trait), trong cc gene khng allele tc ng cng hng ln s biu hin
ca mt tnh trng. Mi allele (thng l tri) ca cc gene a phn nh
55
th ng gp mt phn ngang nhau trong s biu hin ra kiu hnh mt

mc nht nh. Nh vy, liu lng cc allele tng dn trong cc kiu
gene s to ra mt dy bin d kiu hnh lin tc trong qun th.
V d: Cc th nghim ni ting nm 1909 ca nh di truyn hc Thy
in (Sweden) Herman Nilsson-Ehle v s di truyn mu sc ht la m
(ht y tc l phi nh - kernel). Khi lai gia cc ging la m thun
chng ht vi ht trng, F1 ng thu c ton dng trung gian c mu
hng; v ty theo dng ht c s dng trong cc th nghim m F2
s c cc t l phn ly gia ht c mu vi ht khng mu (trng) l 3:1,
15:1 hay 63:1. Kt qu phn tch cho thy chng do 2-3 gene a phn chi
phi. Sau y ta hy xt trng hp F2 vi t l 15 c mu :1 khng mu,
hay c th l 1 : 4 nht: 6 hng: 4 hng nht:1 trng.
Gii thch: Do F2 c 16 kiu t hp vi t l tng ng trong khi F1
ng nht kiu gene, chng t F1 cho 4 loi giao t vi t l ngang nhau
ngha l d hp t v hai cp gene phn ly c lp. y, F1 biu hin
kiu hnh trung gian ca hai b m v F2 xut hin mt dy bin d lin tc
cng hng. iu chng t tnh trng ny tun theo quy lut tc ng
cng gp hay a phn tch ly.
Quy c: V allele cho mu l tri hn allele cho mu trng v
mc biu hin ca cc ht c mu F2 ty thuc vo liu lng cc
allele trong kiu gene, nn ngi ta thng k hiu cc gene khng
allele bng cc ch s 1,2...km theo cc ch ci in hoa (A) cho allele tri
v ch ci in thng (a) cho allele ln, nh sau: A1, A2 - ; a1, a2 - trng.
T y ta c th d dng xc nh kiu gen ca F1 (A1a1A2a2) v ca b
m P: (A1A1A2A2) v trng (a1a1a2a2), v thit lp s lai hnh 2.9.
Ptc
A1A1A2A2 () a1a1a2a2 (trng)
F1
A1a1A2a2 (hng)
F2
Allele tri
Kiu gen
4
1A1A1A2A2
3
2A1A1A2a2
2A1a1A2A2
Kiu hnh
T l
1/16
nht
4/16
2
4A1a1A2a2
1A1A1a2a2
1a1a1A2A2
hng
6/16
1
2A1a1a2a2
2a1a1A2a2
0
1a1a1a2a2
hng nht
4/16
trng
1/16
Hnh 2.9 Mt php lai ca la m v trng do hai gene chi phi, cho
thy mi tng quan gia t l ca cc kiu hnh F2 v s allele tri.
Mt v d c o khc l trng hp di truyn s dy ht trn bp

ng (xem trong Di truyn hc i cng - Dubinin 1981, tr.135-145).
56
Nhn xt: (1)Bng cch v mt th biu din mi quan h gia s

allele tri c mt trong kiu gen (trn trc honh) v cc tn s kiu hnh
(trn trc tung) F2, ta s thu c mt ng cong phn b chun c
dng hnh chung, gi l phn phi Gauss. Trong kiu hnh trung gian
hay cc kiu gene cha hai allele tri (tng ng vi tr trung bnh) chim
t l cao nht, cn cc kiu hnh hoc kiu gene hai u mt tng ng
vi cc ngng "cc oan" bao gi cng chim tn s thp nht (xem
Hnh 2.10). cng l quy lut chung cho tt c cc tnh trng s lng.
(2) i vi cc tnh trng di truyn theo kiu a phn cng gp, cc h s
ca t l kiu hnh c th xc nh bng cch da vo tam gic Pascal.
3.2. Tnh trng s lng (quantitative trait)
Thng thng, cc tnh trng c tr s kiu hnh lin quan n kch
thc, trng lng hay hnh dng...c xc nh da trn thang nh
lng (quantitative scale), c gi l cc tnh trng s lng.
(a)
(b)
Hnh 2.10 M hnh n gin v (a) s phn b chiu cao ngi (n v

tnh y l inch, 1 in = 2,54 cm; trc tung ch s lng); v (b) tng quan
gia cc mc mu da (trc honh) v cc t l trong qun th (trc tung).
Ni chung, cc tnh trng s lng c cc c im sau: Do nhiu gene

quy nh; chu nh hng ln ca cc iu kin mi trng; v c s phn
b kiu hnh lin tc trong mt qun th (hnh 2.10), nhng chng cng c
th xy ra di dng cc lp kiu hnh khc nhau, chng hn nh trong
cc v d v dy mu sc ht la m hoc s dy ht trn bp ng ni
trn. V vy, i vi cc tnh trng ny, khng c mt mi quan h chnh
xc gia tr s kiu hnh v mt kiu gene c th. Chng hn, ngi,
l cc tnh trng v chiu cao, trng lng, hay ch s thng minh
(intelligence quotient - IQ); cy la, la m l s ht trn mi bng,
57
s bng trn mi khm...Tuy nhin, trong nhng nm gn y nh s

dng cc ch th phn t (molecular marker), ngi ta tin hnh lp bn
cc gene c hiu qu ln ln cc tnh trng c bit (nh cc bnh phc
tp ngi, nng sut cy trng...) gi l QTLs, tc cc locus tnh trng
s lng (quantitative trait loci).
nghin cu s bin i kiu hnh ca cc tnh trng s lng, nht
thit phi s dng cc phng php ca thng k ton hc. Chng hn,
phng php ly mu sao cho hp l, ngha l mu phi ln, mang tnh
ngu nhin v i din; vic x l s liu i hi phi s dng mt s i
lng hay tham s thng k c bn sau y:
- Trung bnh cng (mean):
- Bin lng (variance):
x=
vx =
1 n
xi
n i =1
1 n
( xi x) 2
n 1 i =1
- lch chun (standard deviation) bng cn bc hai ca bin lng

(hay phng sai mu).
Mt s i lng khc, nh h s bin thin (coefficient of variation,
Cv%), h s tng quan (r) v.v... c th xem trong cc gio trnh Di
truyn hc s lng v Thng k lin quan (Trn Vn Din v T Cm T
1995; Falconer 1983; Phan Hiu Hin 2001).
3.3. M hnh cc tnh trng s lng
hiu v xc nh c tm quan trng ca cc tnh trng s lng,
ta cn phi xy dng mt m hnh cho php chia ct cc tr s kiu hnh
thnh ra cc thnh phn di truyn v mi trng. iu ny c th thc
hin theo cch n gin bng cch biu th tr s kiu hnh (P: phenotype)
cho mt kiu gene (i) trong mt mi trng c th (j) nh sau:
Pij = Gi + Ei
trong Gi l phn ng gp v mt di truyn ca kiu gene (genotype) i
vo kiu hnh, v Ej l sai lch do mi trng (environment) j. Ej c th
m hoc dng ty thuc vo s tc ng ca mi trng j. Cn lu
rng, trong nhiu trng hp, cc qun th khc nhau c cc tr s trung
bnh khc nhau; v tht kh m xc nh s khc nhau l do cc nhn
t di truyn, nhn t mi trng, hay l s kt hp ca c hai gy ra.
Cc kiu gene khc nhau c th tng tc mt cch khc nhau vi mi
trng ca chng to ra kiu hnh. Nu nh cc mi tng tc c th
nh th xy ra gia cc kiu gene v cc mi trng, khi ta c th m
rng m hnh c s ni trn thnh m hnh tng tc kiu gene-mi
58
trng (genotype-environment interaction), vi tr s kiu hnh l:

Pij = Gi + Ej + GEij
trong GEij l s o s tng tc gia kiu gene i v mi trng j. V
mi trng bin ng nn s tng tc c th m hoc dng.
Ni chung, m hnh di truyn c th c nh ngha mt cch chnh
xc hn bng cch phn chia tr s kiu gene ra hai thnh phn nh sau:
Gi = Ai + Di
trong Ai v Di l cc thnh phn cng gp (additive) v tri (dominant). Nu nh th d hp ng l trung gian gia cc thnh phn ng
hp (nh v d v s di truyn mu sc ht la m ni trn), th s ng
gp ca thnh phn tri l zero; ngha l, ton b thnh phn di truyn l
cng gp. Ni cch khc, nu cho rng s tng tc kiu gene-mi trng
l khng ng k, th tr s kiu hnh c th c biu th bng:
Pij = Ai + Di + Ej
Nh ni t u, khng c s tng ng chnh xc gia mt kiu
gene vi mt kiu hnh i vi cc tnh trng s lng. V vy, cch thc
t hn kim tra cc tnh trng ny l tch s bin i trong mt qun
th i vi mt kiu hnh c th thnh ra hai phn, phn bin i do nhn
t di truyn gy ra v phn bin i do nhn t mi trng gy ra. Khi
phng sai hay bin lng kiu hnh (phenotypic variance) s l:
VP = VG + VE
trong VP, VG v VE tng ng l cc bin lng ca kiu hnh, di
truyn v mi trng. V theo cch lm trn, nu ta tch cc thnh phn
cng gp v tri kim tra bin lng kiu hnh, ta c:
VP = (VA + VD) + VE
trong VA v VD tng ng l cc bin lng di truyn do cc hiu qu
cng gp v tri. Nu ta chia biu thc ny cho VP, lc ta thu c t
l ca bin lng kiu hnh do cc thnh phn khc nhau gy ra. C th l,
t s gia bin lng di truyn cng gp v bin lng kiu hnh c coi
l h s di truyn (h2; heritability):
h2 = VA/VP
i lng h s di truyn ny rt quan trng trong vic xc nh tc v
hm lng p ng i vi s chn lc nh hng (directional selection),
tc chn lc o thi cc kiu hnh cc oan, v n thng c cc nh
chn ging ng vt v thc vt c tnh trc khi bt u mt chng
trnh chn lc nhm ci thin nng sut hoc cc tnh trng khc.
3.3. c lng h s di truyn (heritability)
59
By gi ta th tm hiu vn c lng h s di truyn da trn h

s tng quan ca mt s tnh trng cc cp sinh i cng trng
(monozygotic twins) v sinh i khc trng (dizygotic). Ta bit rng
nhng cp sinh i ging ht nhau (cng trng) th c cng kiu gene; nh
vy bt k s sai khc no gia chng phi l kt qu ca cc nhn t mi
trng. Trn thc t, cc cp sinh i ging ht nhau l do s chia x cng
kiu gene cng nh cc iu kin mi trng nh nhau. Mt cch xc
nh mc tng ng hay ging nhau l tnh h s tng quan r
(correlation) gia cc c th v cc tnh trng khc nhau. Tr s cao nht
ca h s r l 1, trong tt c cc cp c th u c cng tr s kiu hnh
nh nhau. Nu nh cc tnh trng l khng c tng quan gia cc cp c
th th r = 0. Mt kt qu nghin cu v cc h s tng quan ca bn tnh
trng khc nhau cc cp sinh i cng trng (rM) v cc cp sinh i
khc trng (rD) nhng cng gii tnh c cho bng 2.3. Nhng sai khc
gia cc tr s ny phi l kt qu ca s tng ng di truyn thp hn
cc cp sinh i khc trng vn chia x (tnh bnh qun) ch mt na cc
gen ca chng ni chung. Cng thc tnh h s di truyn nh sau:
h2 = 2(rM rD)
trong rM v rD ln lt l cc h s tng quan gia cc cp sinh i
cng trng v khc trng. Bng cch s dng cng thc ny, ta tnh c
cc h s di truyn cho bn tnh trng bng 2.3 bin thin t 0,98 n
0,16. Qua cho thy, hu ht s bin i cc ch s IQ v trng thnh
v mt x hi dng nh l do mi trng, trong khi hu nh s bin i
trong s lng np vn tay v chiu cao dng nh l do di truyn.
Bng 2.3 S tng quan ca bn tnh trng gia cc cp sinh i ngi
Tnh trng
S lng np vn tay
Chiu cao
im IQ
im trng thnh x hi
H s tng quan
rD
rM
0,96
0,47
0,90
0.57
0,83
0,66
0,97
0,89
H s di truyn
0,98
0,66
0,34
0,16
IV. Cc mi quan h kiu gene-kiu hnh

1. Thng bin v mc phn ng
i vi cc tnh trng s lng ni trn, s biu hin ra kiu hnh ca
mt kiu gene no r rng l ty thuc ca cc nhn t mi trng, tc
l ty thuc ty thuc vo thm nhp v biu hin ca kiu gene
(nh chng ta s xt di y). Hay ni cch khc, kiu hnh l kt qu
ca s tng tc gia kiu gene v mi trng.
60
Trong mt tnh hung l tng, phm vi tc dng ca mi trng ln

mt kiu gene no c th xc nh c bng cch quan st kiu hnh
ca cc c th ging nhau v mt di truyn c nui dng chm sc
trong cc mi trng khc nhau. ngi, cc cp sinh i cng trng
c tch nui ring lc s sinh chng minh cho mt tnh hung nh
vy. Tuy nhin, nhng ch dn tt nht v cc tc dng ca mi trng bt
ngun t cc nghin cu loi m c th nui trng vi s lng ln trn
cc mi trng c kim sot.
Th d kinh in cho nghin cu nh vy c J.Clausen v cc cng
s tin hnh trong thp nin 1940. xc nh hiu qu ca mi trng
ln cc kiu hnh, cc nh nghin cu ny trng cc dng (clones), tc
gm cc c th ging nhau v mt di truyn, ct theo cc v khc nhau.
Chng hn, h thu thp loi thuc h hoa hng l Potentilla glandulosa
t ba vng: phm vi ven b bin Thi Bnh Dng v 100 mt; vng
lng chng dy ni Sierras v 1.400 mt (ngn Mather); v cao
3.040 mt ca dy Sierras (ngn Timberline). T cc mu ny, h to ra
c cc dng bng cch nhn ging sinh dng v em trng ba vng
khc nhau . Ni khc i, mi kiu gene thu c t mt trong ba vng
c a trng c ba iu kin mi trng (ng vi cc v ) khc
nhau. T th nghim ny cho thy rng dng nh c hai nhn t di truyn
v mi trng u quan trng trong vic xc nh s sinh trng ca cy.
Th d, cc kiu gene vng ven b sinh trng tt c v thp v trung
bnh nhng nhng khng th sng c v cao. iu ch ra tm
quan trng ca cc nhn t di truyn.
Cch thc m kiu hnh thuc mt kiu gene no thay i theo mi
trng ca n c gi l mc phn ng (norm of reaction). Cc mc
phn ng c th sai khc rt ln trong s cc kiu gene i vi cc tnh
trng lin quan n tp tnh hay hnh vi (behaviour). D cho n nay ta
khng h xem tp tnh hay hnh vi nh l mt kiu hnh, th nhng mt s
cc gene t bin c nh hng ln tp tnh hay hnh vi. Chng hn, cc
c th b bnh PKU khng c iu tr th c cc ch s IQ thp hn bnh
thng; IQ l mt tnh trng c th o c bng trc nghim IQ.
Tm li, mi quan h gia kiu gene v kiu hnh l phc tp, khng
d g cn c vo kiu hnh xc nh kiu gene. Mc phn ng trn cc
mi trng khc nhau l mt cch nh lng mi quan h .
2. thm nhp (penetrance) v biu hin (expressivity)
nh gi mc th hin ra kiu hnh ca cc kiu gene nh th,
nm 1925 Timofeev-Rissovsky nu ln hai khi nim: thm nhp v
biu hin ca gene.
61
2.1. thm nhp (penetrance)

Trong cc th d xt trc y, nh by gene xc nh by tnh
trng u H Lan, cc kiu nhm mu v nhiu bnh di truyn ngi
u cho thy mt kiu tuyt i chc chn. Tuy nhin, i vi mt s
gene, th mt kiu gene no c th hoc khng th cho thy mt kiu
hnh no . Hin tng ny c gi l thm nhp (penetrance) ca
mt gene. Mc thm nhp (level of penetrance) ny c th tnh bng t
l ca cc c th mang mt kiu gene no bc l ra mt kiu hnh c
th. Khi tt c cc c th ca mt kiu gene c th c cng kiu hnh nh
nhau, th gene cho thy thm nhp hon ton v mc thm nhp
ny c coi l bng 1. Mt khc, gene c coi l thm nhp khng han
ton v mc thm nhp c th c th tnh c. Chng hn, trong s 160
c th thuc mt kiu gene no c 30 c th biu hin mt kiu hnh b
bnh, th mc thm nhp l 30/160 = 0,1875; ngha l gene ch th
hin ra c kiu hnh c 18,75%.
Nh vy s c mt ca thm nhp khng hon ton ti mt gene c
th khin cho mt kiu hnh tnh trng tri (gi s kiu gene l Aa) b ngt
qung mt th h trong mt ph h, ri li xut hin tr li th h tip
theo. l do allele tri thm nhp khng hon ton. Chng hn, dng tri
ca nguyn bo li (retinoblastoma), mt bnh gy cc u c tnh mt
tr em, ch thm nhp khong 90%.
2.2. biu hin (expressivity)
Ngoi ra, mt kiu gen c th no bc l ra kiu hnh k vng, tc
mc biu hin (level of expression) hay biu hin (expressivity), c
th sai khc i. Chng hn, mc d mt gene gy ra mt bnh c th pht
hin c hu ht cc c th mang mt kiu gene no , nhng mt s
c th c th b nh hng nng hn cc c th khc.
Bnh Huntington ngi l mt tnh trng cho thy biu hin bin
thin sai khc theo tui pht bnh. Bnh ny ni chung xy ra tui
bt u trung nn, vi tui trung bnh bt u pht bnh l trn 30 tui,
nhng i khi c th xy ra rt sm tui cha ln 10 hoc mt ngi
gi hn. Mt s ngi mang kiu gene bnh ny cht v nhng nguyn
nhn khc trc khi bnh biu hin, do thm nhp khng hon ton
cng nh biu hin bin thin i vi gene gy ra.
2.3. Cc nhn t mi trng v cc gene khc
2.3.1. Mi trng v cc gene gy cht c iu kin
Vn t ra l ci g l nguyn nhn ca thm nhp khng hon
ton v biu hin sai khc? Trong mt s trng hp c th, thng thf
62
khng th xc nh c nguyn nhn, nhng c mi trng v cc gen

khc cng c coi l c nh hng ln thm nhp v biu hin ca
mt gene. V d, rui gim, cc allele ca mt s gene tc ng ln sc
sng v c th gy cht nhit tng cao trn 28oC nhng li nh hng
cht t hoc khng nh hng nhit thp hn. Cc gene nh th gi l
cc gene gy cht c iu kin (conditional lethals); ni chung chng cho
thy cc hiu qu gy cht trong cc tnh hung mi trng cc oan.
Nhit cng c th nh hng mnh m ln kiu hnh ca cc thc
vt. Chng hn, cy anh tho c hoa khi
trng 24oC nhng li c hoa trng khi trng
nhit trn 32oC. mo Xim (Thi
Lan) v th Himalaya, mu sc b lng ca
chng ti sm hn chn, tai v mi ti v
thn nhit cc b phn xa nht ca c th
ny t ra thp hn. Nu nh chng nhit
Hnh 2.11 Mu lng ca mo Xim ti sm cc vng chn, tai v mi.
m p hn, th s sinh trng lp lng mi ti cc im ny s cho

mu sng nht (hnh 2.11).
2.3.2. Cc gene sa i (modifier or modifying genes)
Ni chung, mc biu hin ca mt tnh trng gia cc c th c
quan h h hng thng ging nhau hn l gia cc c th khng c quan
h h hng, khi c hai nhm c th c nui dng chm sc trong
nhng mi trng gn ging nh nhau. Cc gen c nh hng th cp ln
mt tnh trng nh th gi l cc gene sa i (modifier genes) v chng
c th gy nh hng ln kiu hnh mt cch ng k. Ni cch khc, cc
gene sa i l nhng gene gy bin i cc gene khc trong khi chng
biu hin ra kiu hnh.
Hnh 2.12 Thy tinh th bnh thng (tri) v bnh c thy tinh th (phi)
do mt gen tri gy ra c tc ng ca gene sa i.
nhiu ng vt, allele pha long (dilute allele) vn lm gim cng

hnh thnh sc t (nh t mu en sang mu xm chut nh) khi
63
trng thi ng hp l mt v d v gene sa i. Mc ca hin tng

khng ui cc mo Manx bin thin t khng c cc t sng ui cho
n c mt t t sng ui dnh lin nhau, hnh nh l do nh hng ca
cc gene sa i ln s biu hin ca th t bin tri ny. ngi, l
trng hp mt gene tri gy c thy tinh th (hnh 2.12). Gene ny gy
ra nhng mc suy yu th lc khc nhau ty thuc vo s c mt ca
mt allele c th v mt gene sa i i cng.
2.3.3. Hin tng sao hnh (phenocopy)
Mt hin tng lin quan gi l sao hnh (phenocopy), xy ra khi cc
nhn t mi trng gy ra mt kiu hnh c th m thng thng c xc
nh v mt di truyn. Trong trng hp ny, mt mi trng cc oan c
th lm gin on s pht trin bnh thng bng mt kiu ta nh ca
mt gene t bin. Mt trng hp thm thng xy ra cc nc Ty
u vo cui thp nin 1950 v u thp nin 1960 khi mt s lng cc
chu b sinh ra c t chi b ngn i mt cch kinh khng. Hin tng bt
thng ny ging vi mt dng ri lon di truyn ln. Ch sau khi c mt
cuc nghin cu rng ri ngi ta mi hay rng dng khuyt tt c
gy ra v mt mi trng bi s b sung thalidomide vo bo ch vin
thuc ng m cc b m ca cc chu b b bnh ung trong sut thi
k u mang thai.
Cu hi v Bi tp
1. Hy ch ra cc mi quan h gia gene v tnh trng. Phn bit cc
kiu tng tc gia cc gene khng allele ln s hnh thnh mt tnh trng.
2. c trng ca cc tnh trng s lng l g? Phn bit cc cp khi
nim sau: tnh trng s lng v tnh trng cht lng, thm nhp v
biu hin, tng tc gia cc gene allele v cc gene khng allele.
3. Mt ph n nhm mu M c mt a con mang nhm mu MN. B
ta ni rng mt ngi n ng no c nhm mu MN l b ca n, v
ng y tuyn b khng phi nh vy. (a) Vi thng tin , bn c th loi
tr ngi n ng ny vi t cch ngi b khng? (b) Vic nghin cu
xa hn cho thy ngi n b ny mang nhm mu B, a con mu O, v
ngi n ng kia nhm mu AB. Vi thng tin ny, c th gt ngi n
ng kia ra khi t cch ngi b hay khng? Ti sao?
4. c mo, cc php lai gia cc c th lng v bc i khi sinh ra
tt c lng ; i khi : bc; v i lc l : trng: bc.
Cc php lai gia hai con lng sinh ra hoc l ton b ; hoc :
trng; hoc : bc. Hy xc nh phng thc di truyn ca tnh
64
trng ny v kiu gene ca cc c th khc nhau tham gia vo cc php lai.

5. th, mu sc lng do bn allele ca mt gene n kim sot. Th
t tri ca cc allele nh sau: C- xm > ca - sc len > cb - Himalaya > c bch tng. Ngoi ra, cc kiu gene cacb v cac u cho mu xm nht.
Kt qu lai gia mt th xm vi ba con th khc nh sau:
Php lai
i con
Xm sc len
6 xm, 5 xm nht
Xm xm nht
8 xm, 3 xm nht, 4 himalaya
Xm bch tng
9 xm, 8 himalaya
Hy ch ra phng thc di truyn v kiu gene ca cc th b m.
6. Cc mu sc ca mt loi thc vt c th l , hng hoc trng. T
kt qu di y, hy bin lun xc nh phng thc di truyn ca
tnh trng mu hoa v ch ra cc kiu gene ca cc ging em lai.
Php lai
i con
-1 Hng
: hng
-1 Trng
: hng
-2 Hng
: hng : trng
-3 Hng
Tt c
-3 Trng
Tt c
7. Mu tc ngi gm c nm sc : vng, nu nht, nu va, nu
thm v en. Cc php lai gia cc mu tc khc nhau cho kt qu sau:
(1) vng vng tt c vng;
(2) en en tt c en;
(3) vng nu va tt c nu nht; hoc vng : nu va;
(4) nu va nu va tt c nu va; hoc nu thm : nu
nht; hoc nu va: en : vng.
Hy xc nh kiu gene ca nm mu tc, v cho bit: (a) Nu lai gia
nu nht v nu thm, t l k vng kiu hnh sinh ra nh th no?
8. chut, bt k c th no c cc l bch tng (albino). Hai cp allele
khc, A/a v B/b, khi c mt allele C s cho mu xm, en, nu vng v
nu sm. Bn dng thun chng bch tng khc nhau v kiu gene c
cho giao phi vi cc con lng xm thun chng (AABBCC). Tt c chut
cc i F1 u mu xm. Sau cc chut F1 t mi php lai c cho
giao phi gia chng vi nhau, v kt qu cc i F2 nh sau y. Hy xc
nh kiu gene mi dng bch tng.
65
Dng albino
1
2
3
4
Xm
44
31
48
145
en
0
0
15
43
Nu vng
16
0
0
46
Nu sm
0
0
0
15
Bch tng
20
9
21
82
9. mt loi thc vt, khi lai gia mt dng hoa ta thun chng v
ba dng hoa trng thun chng khc nhau vi kt qu cho nh sau:
Php lai 1
Php lai 2
Php lai 3
ta trng-1
ta trng-2
ta trng-3
F1
18 ta
17 ta
19 ta
F2
95 ta
31 trng
80 ta
36 trng
28
54 ta
32 trng
19
17 xanh da tri
6 nu
Hy bin lun v xc nh: (a) kiu gene ca bn ging hoa b m; (b)

t l kiu hnh ca i con nu F1 ca php lai 2 c lai vi trng-2; (c)
t l kiu hnh ca i con nu F1 t php lai 3 c cho lai vi trng-3.
10. Khi lai hai ging ng thun chng c 20 dy ht v 8 dy ht, tt
c bp ng F1 u c 14 dy ht, v F2 c by kiu hnh khc nhau: 20,
18, 16, 14, 12, 10 v 8 (dy ht) vi s lng thng k tng ng l 40 :
245 : 594 : 793 : 603 : 236 : 38 (bp ng). Phng thc di truyn ca tnh
trng ni trn l g? Gii thch, trnh by s lai v minh ho kt qu F2
bng mt th. Bn th rt ra quy lut chung v s di truyn ca loi tnh
trng ny v ch ra cch xc nh t l kiu hnh k vng F2 i vi
trng hp mt tnh trng c kim sot bi n locus c lp.
Ti liu Tham kho

Ting Vit
Trn Vn Din v T Cm T. 1995. Di truyn s lng (Gio trnh cao
hc Nng nghip). NXB Nng Nghip, H Ni.
Dubinin NP. 1981. Di truyn hc i cng (bn dch ca Trn nh Min
v Phan C Nhn). NXB Nng Nghip, H N.
Hutt FB. 1964. Di truyn hc ng vt. (Bn dch ca Phan C Nhn).
NXB Khoa hc v K thut, H Ni, 1978.
66
Phan Hiu Hin. 2001. Phng php b tr th nghim v x l s liu

(Thng k thc nghim). NXB Nng Nghip Tp.H Ch Minh.
truyn hc. NXB Gio Dc, H Ni.
Ting Anh
Boon WH. 1984. Genes and the IQ. PG Publishing Pte Ltd, SingaporeHong Kong-New Dehli.
Clegg CJ, Mackean DG. 2000. Advanced Biology: Principles and
Applications. 2nd ed, John Murray Published Ltd, London.
Falconer DS. 1983. Introduction to Quantitative Genetics. 2nd ed.,
Longman, London and New York.
Companies, Inc. Wm.C.Browm Publishers, Dubuque, IA.
Wellnitz WR. 1995. Genetics: Problem Solving Guide. 2nd ed., Wm.C.
Brown Publishers. Dubuque, Iowa.
Mt s trang web
http://www.biology.about.com/library/weekly/aa122602a.htm
http://gslc.genetics.utah.edu/units/basis/
http://mhhe.com/lewisgenetics5
http://www.goodnet.com/nee72478/enable/hotline.htm
http://www.cff.org
http://consensus.nih.gov
67
Chng 3
C s T bo ca s Sinh sn,
Di truyn v Bin d
Nh chng ta u bit, cc khm ph ca Mendel v nhng nghin
cu v cu trc t bo trong na cui th k XIX vn cn cha c s gn
kt vi nhau. Vo nm 1902, Walter Sutton (USA) v Theodor Bovery
(Germany), da trn tp tnh tng t ca cc gene v nhim sc th
(chromosome) trong qu trnh gim phn gi rng cc gene c l nm
trn cc nhim sc th. Sutton nhn nh: "Cui cng, ti xin lu rng
xc sut kt hp ca cc nhim sc th b v m theo cc cp v phn ly
sau trong s phn chia gim nhim... to thnh c s vt l cho cc quy
lut di truyn Mendel". Ngy nay, iu y qu hin nhin. Nhng vo thi
nhn nh ny ht sc quan trng; n to ra s kt ni cht ch gia di
truyn hc v t bo hc, hnh thnh nn lnh vc mi gi l di truyn hc
t bo vi s ra i ca thuyt di truyn nhim sc th.
Trong chng ny, chng ta s tm hiu cc nhim sc th c hnh thi
c trng nh th no; bng cch no s lng nhim sc th c duy tr
n nh trong qu trnh nguyn phn, nhng li gim i mt na trong qu
trnh gim phn; v cc kiu bin i v cu trc v s lng nhim sc
th (t bin nhim sc th).
I. Sinh sn hu tnh v tnh n nh ca b nhim sc th

Trc tin, ta cp ch yu phng thc sinh sn hu tnh
eukaryote v mi lin quan gia n vi s n nh v s lng nhim sc
th c trng ca mi loi. Thc ra, cc eukaryote c hai kiu sinh sn
chnh, v tnh v hu tnh.
S sinh sn v tnh (asexual reproduction) xy ra khi mt c th n
c to ra mt c th mi ging n; y l phng thc sinh sn ph bin
thc vt v cc ng vt n gin. S trinh sinh (parthenogenesis) rp
ci chng hn l mt trng hp c bit, cng sinh con nhng khng qua
th tinh. Ni chung, con ci sinh ra bng cch ny th ging vi b m v
mt di truyn.
S sinh sn hu tnh (sexual reproduction) xy ra khi cc c th to ra
cc t bo sinh dc c v ci, hay cc giao t (gametes), n lt chng
kt hp vi nhau to thnh mt t bo trng c th tinh gi l hp t
(zygote), tc mt t bo hon chnh m t pht trin thnh mt c th
mi. Hnh thc sinh sn ny xy ra hu nh ton b cc kiu sinh vt, k
68
c cc ng vt n gin nht nh con sum (Balanus) chng hn, cc thc

vt, v thm ch c vi khun. vi khun, c cc kiu trao i thng tin di
truyn nh tip hp, bin np v ti np c gi l sinh sn cn tnh
(parasexual; vn ny c trnh by ring trong gio trnh Di truyn Vi
sinh vt v ng dng). Thng thng th cc giao t c v ci bt ngun
t cc c th khc nhau, cho nn i con sinh ra khc vi b m chng v
nhiu chi tit. y l ni dung chnh m chng ny s tp trung tho
lun. Cn s t th tinh c xem l trng hp ngoi l quan trng ca
sinh sn hu tnh (xem chng 12).
Hp t ci (N)x Con ci trng thnh G Trng
(2n)
(2n)
(n)
Hp t
(2n)
Hp t c (N)x Con c trng thnh G Tinh trng

-------------[Sinh trng]------------------- * ----[Pht sinh]---- * --[Th tinh]-giao t / bo t
Hnh 3.1 S tng qut v sinh trng v sinh sn sinh vt hu tnh.

y cho thy s lng nhim sc th lng bi (2n) v n bi (n) tng ng
vi cc giai on khc nhau (hng di cng). K hiu (N)x biu th nhiu ln
nguyn phn, v G - gim phn.
S tng qut v s sinh trng v sinh sn ca sinh vt sinh sn

hu tnh c trnh by hnh 3.1. Trn nguyn tc, mi hp t nhn
c hai b nhim sc th n bi (haploid) k hiu l n, mt t giao t
c v mt t giao t ci; nn s lng nhim sc th trong hp t l
lng bi (diploid), tc 2n c trng v n nh cho loi. Mi b n bi
cha n nhim sc th khc nhau, mi chic hay kiu nhim sc th ch c
mt mt ln v cha cc gene khc nhau. Tp hp ton b cc gene trong
mt b nhim sc th n bi nh th c gi l b gene (genome). Nh
vy, trong b lng bi c trng ca cc t bo soma, cc nhim sc th
tn ti theo tng cp gm hai chic ging nhau v hnh dng, kch thc
v trt t phn b cc gene - mt c ngun gc t b v mt t m - gi l
cc nhim sc th tng ng (homologous chromosomes).
sinh vt a bo, hp t tng s lng t bo nh qu trnh nguyn
phn (mitosis), l kiu phn chia t bo to ra cc t bo con c s lng
nhim sc th 2n c gi nguyn. Khi c th t ti thnh thc sinh
dc, mt s t bo ca c quan sinh sn tri qua gim phn (meiosis), tc
kiu phn chia t bo to ra cc giao t c s lng nhim sc th gim i
69
mt na (n). Qu trnh ny c gi l pht sinh giao t (gametogenesis)

ng vt v pht sinh bo t (sporogenesis) thc vt. Sau , trong
qu trnh th tinh (fertilization), cc giao t ci hay trng (egg) v giao t
c hay tinh trng (sperm) hp nht vi nhau to thnh cc hp t i
con. Cc hp t mi ny li bt u i vo mt chu k sinh trng v sinh
sn y ht nh vy.
Bng 3.1 S lng nhim sc th 2n ca cc t bo soma mt s loi
Loi ng vt
2n
Loi thc vt
Ngi (Homo sapiens)
46 u H Lan (Pisum sativum)
Chimpanzee (Pan troglodites) 48 Ng (Zea mays)
B (Bos taurus)
60 La go (Oryza sativa)
Nga (Equus caballus)
64 La mch (Secal cereale)
La (Equus asinus)
62 La m (Triticum durum)
Ch (Canis familiaris)
78 La m (Triticum vulgare)
Mo (Felis catus)
38 Khoai ty (Solanum tuberosum)
Chut nht (Mus domesticus)
40 Thuc l (Nicotiana tabacum)
G (Gallus domesticus)
~78 Loa kn (Lilium longiflorum)
ch c (Rana pipiens)
26 Mn (Prunus domestica)
C chp (Cyprinus carpio)
104 Bng (Gossypium hirsutum)
Rui gim (D. melanogaster)
8
Hng dng (Helianthus annuus)
2n
14
20
24
14
28
42
48
48
12
48
52
34
Mi loi c mt s lng nhim sc th c trng; ngha l tt c cc

c th ca cng mt loi th c s lng nhim sc th nh nhau. S lng
nhim sc th ny hu ht cc loi ng-thc vt l lng bi (2n) c
gii thiu bng 3.1, v mt s loi l n bi (n) - theo ngha c pha
n bi l chnh - nh cc nm mc bnh m hng (Neurospora crassa, n
= 7), mc bnh m en (Aspergillus nidulans, n = 8), nm men bia
(Saccharomyces cerevisiae, n = 17)...R rng l s lng nhim sc th
khng tng ng vi nc thang tin ha ca cc loi. Tuy nhin, ta c th
thy cc loi c quan h h hng gn nhau nh ngi v chimpanzee hay
nga v la th c s lng nhim sc th gn bng nhau. Cng cn lu
rng, mt s loi thuc b cnh mng Hymenoptera nh ong mt (Apis
mellifera) chng hn, con ci l 2n = 32 v con c l n = 16. i vi cc
sinh vt ny ngi ta dng thut ng l n-lng bi (haplodiploid).
mt s loi ng-thc vt nh ng, la mch en... bn cnh cc nhim
sc th chun ca b nhim sc th bnh thng (gi l cc nhim sc th
A), cn c thm mt vi nhim sc th rt b vn sai khc gia cc c th,
gi l cc nhim sc th tha s (supernumerary chromosomes) hay nhim
70
sc th B, phn bit vi cc nhim sc th A. Cc nhim sc th ny

c coi l khng cha cc gen quan trng, mc d trong mt vi trng
hp chng nh hng ln hu th. a s loi thuc lp chim (Aves),
b nhim sc th cha cc nhim sc th rt nh gi l cc vi nhim sc
th (microchromosomes) v thng c s lng ln.
II. Hnh thi hc nhim sc th eukaryote

tm hiu su hn v cu trc v chc nng ca cc nhim sc th, ta
cn phi phn bit gia cc nhim sc th khc nhau v cc im sau y.
1. Kch thc nhim sc th
Kch thc cc nhim sc th sai khc nhau rt ln. Gia cc loi khc
nhau s sai khc ny c th ln ti hn 100 ln, trong khi mt s nhim
sc th trong mt loi c kch thc hn km nhau khong 10 ln.
v tr tm ng
chiu di
kiu bng
(a)
(b)
Hnh 3.2 (a) B nhim sc th c x l bng thuc nhum ph bin
Giemsa; v (b) xc nh cc c im ca mt nhim sc th.
m t b nhim sc th ca mt loi v xc nh cc nhim sc th

ca n, cn phi thit lp kiu nhn (karyotype) v v s dng mt h
thng cc quy c da trn kch thc ca chng, v tr tm ng, v cc
kiu bng (cc hnh 3.2 v 3.5). Theo truyn thng, ngi ta s dng k
thut hin bng (v d bng G hnh 3.2; xem thm mc 3) v chp nh
cc nhim sc th k gia ca nguyn phn, gi l phng php k gia.
Sau phng i nh, ct ri tng chic (gm hai chromatid ch em) v
sp thnh tng cp tng ng (vai ngn quay ln trn v vai di hng
xung di), ri xp theo th t nh dn v kch thc v nh s t ln
nht n nh nht. Chng hn, i vi ngi (xem cc hnh 3.3 v 3.5): (i)
cc nhim sc th khng phi gii tnh gi l nhim sc th thng
(autosome) c nh s t 1 n 22 trn c s chiu di, cn cc nhim
sc th gii tnh X v Y c tch ring. (ii) Vai ngn ca nhim sc th
c biu th bng p v vai di bng q da trn v tr ca tm ng. (iii)
mi vai trc tin c chia thnh cc vng v sau c xc nh bng
cc bng. V d, k hiu 9q34 c ngha l vai di ca nhim sc th s 9,
71
vng 3, v bng 4. y l ni khu tr ca gene xc nh h nhm mu

ABO.
Hnh 3.3 B nhim sc th ngi c thit lp bng phng php mi kiu nhn ph (spectral karyotype). Ngun: Schrock v cs (1996).
Gn y, Schrock v cs (1996) gii thiu cc phng php thit lp

kiu nhn mi s dng cc thuc nhum hunh quang c kh nng bm
vo cc vng c th ca cc nhim sc th, gi l thit lp kiu nhn ph
(spectral karyotyping; Hnh 3.3). Bng cch s dng mt lot cc vt d
(probes) c th c hm lng cc thuc nhum khc bit, cc cp nhim
sc th khc nhau s c cc c trng ph ring. Mt c im dc o
ca cng ngh ny l s s dng mt nhiu k (interferometer) ging nh
cc nh thin vn dng o quang ph pht ra t cc v sao. Cng ngh
ny cho php pht hin cc bin i nh v mu sc (m mt thng
chng ta khng th pht hin) bng chng trnh my tnh ri sau phn
loi tng cp nhim sc th theo cc mu sc khc nhau. Vic sp xp cc
nhim sc th theo tng cp rt n gin v cc cp tng ng th c
cng mu nh nhau, v cc sai hnh hoc cc trao i cho c th nhn
bit c mt cch d dng hn.
2. Tm ng v cc kiu nhim sc th
Cc nhim sc th thng khc nhau v v tr tm ng (centromere),
l ni m cc si thoi bm vo trong qu trnh phn bo (hnh 3.4).
Thng th mi nhim sc th ch c mt eo tht ln cha mt tm ng
gi l eo s cp (primary constriction). (Thut ng kinetochore dng
ch cu trc protein bao quanh vng tm ng). Ni chung, c ba kiu
72
nhim sc th chnh: nu tm ng nm gn chnh gia, gi l nhim sc

th tm gia (metacentric); nu tm ng nm lch v mt u, gi l
nhim sc th tm u (acrocentric); v nu tm ng gn st u mt,
gi l nhim sc th tm mt (telocentric). Ni cch khc, tm ng chia
nhim sc th thnh hai vai hay cnh (arms) di ngn khc nhau; chng
hn, trong khi nhim sc th tm gia c hai vai gn nh bng nhau, th
nhim sc th tm lch c mt vai ngn v mt vai di. Cc kt qu nghin
cu cho thy chut nh tt c 40 cp nhim sc th u thuc kiu tm
gia, trong khi b nhim sc th ngi gm hai kiu tm gia v tm
u, khng c kiu tm mt (hnh 3.3). Ngoi eo s cp, trn mt s
nhim sc th c th cn c th c eo th cp (secondary constriction), v
nu eo ny gn u mt v xy ra s tht su s to nn mt v tinh
(satellite) ca nhim sc th ( ngi, l cc nhim sc th 13, 14, 15,
21 v 22; xem hnh 3.5b). Eo th cp thng cha cc gene tng hp cc
RNA ribosome, tch t tm thi v hnh thnh nn t chc gi l hch
nhn (nucleolus); n c mt trong nhn (nucleus) mt s giai an khc
nhau ca s phn bo. Hai u mt ca mi nhim sc th eukaryote c
cu trc c bit gi l telomere (s c tho lun chng 5) v thng
c trnh t DNA khc vi phn cn li ca nhim sc th.
B i
Cc chomatid khng ch em
Cc chromatid
ch em
Cp tng ng
(a)
(b)
Hnh 3.4 (a) Mt cp nhim sc th tng ng kiu tm u k gia. (b)
Mi chic ly ra t nhn k gia gm hai chromatid ch em dnh nhau tm
ng, gi l b i (dyad) v c cc u mt c trng gi l telomere.
3. Cc kiu bng nhim sc th (chromosomal bands)

Ngi ta c th xc nh cc vng khc nhau trn cc nhim sc th
bng cc k thut hin bng (band techniques) c x l cc ha cht khc
nhau, nh cc bng G, Q v R (tng ng l Giemsa, quinacrine v
reverse bands- bng o ngc) (xem Verma v Babu 1995). Thc ra,
thut ng chromosome (= chromo: mu + soma: th) theo ngha en c
73
ngha l "th bt mu". Cc k thut s dng cc thuc nhum khc nhau

xc nh cc vng ca nhim sc th no lm hin ra cc vch, di
hay bng (bands) c m nht, sng ti hoc hin th bng cc mu
khc nhau. Chng hn, cc bng sm hn thng xut hin gn tm
ng hoc cc u mt (telomeres) ca cc nhim sc th, trong khi cc
vng khc bt mu yu hn nn nht hn. Cc vng bt mu m gi l
cht d nhim sc (heterchromatin) v cc vng bt mu nht gi l cht
ng nhim sc (euchromatin). Ni chung, cc vng c trng ny c
duy tr n nh trong cc t bo hay cc c th khc nhau ca mt loi v
do chng t ra hu ch cho vic xc nh cc nhim sc th c th.
Hnh 3.5 trnh by kiu nhn v biu nhim sc th (idogram) ngi.
(a)
(b)
Hnh 3.5 (a) Kiu nhn, v (b) biu nhim sc th ngi.
Ngun: Current Opinion in Genetics & Development (1998)
Cc vng euchromatin thng tri qua mt chu k ng v m xon

u n, tng ng vi s hot ng ca hu ht cc gene khu tr trn .
Cc vng heterochromatin gm hai kiu: n nh (constitutive) v khng
n nh (facultative). Heterochromatin n nh, tc l phn c nh ca b
gene v khng bin i c thnh euchromatin; chng c coi l bt
hot v mt di truyn. Ngc li, heterochromatin khng n nh bao gm
c euchromatin l nhng vng bt gi mu v c c (theo ngha ng
xon cht) c trng ca euchromatin trong mt s giai on pht trin;
hay ni cch khc, thc cht l cc vng euchromatin nhng ch bin
i thnh heterochromatin trong k trung gian (interphase) mt s m.
Trn thc t, ngi ta cn pht hin mt s dng nhim sc th c
bit c kch thc khng l, nh: (i) cc nhim sc th kiu chi lng hay
bn chi n (lampbrush chromosomes) bt gp trong non bo s cp ca
74
ng vt c xng sng (c th di ti 1mm nh lng th c ui); v

(ii) cc nhim sc th a si (polytene chromosomes) c mt trong nhn t
bo tuyn nc bt ca u trng b hai cnh (Diptera).
(a)
(b)
Hnh 3.6 (a) Nhim sc th khng l trong mt nhn t bo truyn nc
bt ca u trng D. melanogaster, v (b) cu trc chi tit ca nhim sc th
X c tch lm hai na, mi na c 10 vng v mi vng bt u bng mt
bng mu m.
Chng hn, rui gim D. melanogaster, cc nhim sc th a si ny

sinh ra do hin tng ni nguyn phn (endomitosis), tc cc nhim sc
th t nhn i lin tip c chc ln nhng t bo khng phn chia v hu
nh trng thi m xon. V vy chng c th cha ti c ngn si
chromatid dnh nhau trong mt b, vi chiu di hn100 ln so vi cc
nhim sc th bnh thng (hnh 3.6). V xc nh c tt c l 102
vng, vi hn 5.000 bng. Ring mt mnh nhim sc th X (tc nhim
sc th s 1) c 20 vng c nh s t 1 n 20, vi hn 1.000 bng.
hnh 3.7b cho thy n l nhim sc th tm mt, c tm ng vng 20
nm st u mt bn phi ca na di, v gene gy ra mt trng nm gn
u mt bn tri vng 3 thuc na trn.
III. Chu k t bo v nguyn phn

Nguyn phn (mitosis) l qu trnh phn chia t bo trong cc t
bo con c to ra c s lng nhim sc th ging vi cc t bo b m.
Kiu phn bo ny c trng cho cc t bo soma, k c cc t bo sinh
dc (2n) pha sinh sn ca s pht sinh giao t cc ng-thc vt (mc
IV.2), v xy ra theo cp s nhn vi cng bi bng 2, ngha l: t mt t
bo ban u tri qua k ln nguyn phn lin tip s cho ra 2k t bo ging
75
n. Nh vy m c th ln ln v cc t bo trong c th thng xuyn

c i mi. Quy lut phn bo ny c minh ha n gin nh sau:
1 2 4 8 16 32 64 128 256 512 ...
1. Chu k t bo (cell cycle)
Qu trnh nguyn phn lp li theo chu k nh vy c gi l chu k
nguyn phn hay chu k t bo (cell cycle). Nguyn phn l mt phn ca
ton b chu k t bo i vi cc t bo tri qua nguyn phn (nh hp t,
cc t bo phi, cc t bo thuc cc m sinh trng hay m phn chia;
hnh 3.7a). Ni chung, mt chu k t bo bao gm hai giai on chnh l
nguyn phn (k hiu: M), l mt phn tng i nh ca ton b chu k
(a)
(b)
T bo
ngng
phn chia
Hnh 3.7 (a) S phn chia ca cc t bo chp r hnh ty (Allium cepa).

(b) S tng qut ca mt chu k t bo.
t bo, v phn cn li ca chu k t bo gi l k trung gian (interphase).

Gi l k trung gian bi v n nm gia hai ln phn chia lin tip. y l
giai on t bo din ra cc hot ng chuyn ha cao , tng hp v ti
bn vt cht di truyn - DNA, chun b tch cc cho t bo bc vo
nguyn phn. N c chia thnh ba phn, gi l G1, S v G2. Nh vy,
theo nguyn tc, mt chu k t bo bao gm bn giai on theo th t sau
y (hnh 3.7b): (1) G1 (first gap) = giai an khi u trong t bo sinh
trng, chuyn ha v chun b cho s ti bn b gene; (2) S (DNA
synthesis) = tng hp DNA (v chi tit, xem chng 5); (3) G2 (second
gap) = chun b cho qu trnh nguyn phn; v (4) M = nguyn phn
(mitosis). Thi gian ca cc giai on khc nhau trong chu k t bo khc
nhau mt cch ng k, ty thuc vo tng loi, tng kiu t bo, nhit
v cc nhn t khc. Chng hn, thi lng tng ng vi bn giai on
G1, S, G2 v M i vi cc t bo mu trng ca ngi ang phn chia l
11, 7, 4 v 2 gi (thi gian ton b l 24 gi).
Khi mt hp t va c hnh thnh hay mt c th ang sinh trng,
76
chu k ny c lp li nhiu ln hnh thnh nn mt c th vi hng t

t bo. Mt s kiu t bo trng thnh, nh cc t bo thn kinh v t bo
c vn gi nguyn k trung gian, thc hin cc chc nng c bit
ha trong c th cho n lc cht v khng bao gi phn chia na; giai
on c gi l pha G0. Tuy nhin, mt s t bo c th t pha G0
quay li i vo chu k t bo. Mc d hu ht cc t bo lympho trong
mu ngi pha G0, nhng nu c s kch thch thch hp nh khi bt gp
khng nguyn ph hp chng hn, chng c th b kch thch quay li
chu k t bo. C th ni, G0 khng n thun ch ra s vng mt ca cc
tn hiu cho nguyn phn m l mt s c ch hot tnh ca cc gene cn
thit cho nguyn phn. Cc t bo ung th th khng th i vo pha G0 v
c nh trc lp li chu k t bo mt cch v hn (xem chng 5).
K trung gian
u k trc
Cui k trc
K gia
K cui
K sau
Hnh 3.8 S biu din cc k ca nguyn phn v chu k ca n.
2. Nguyn phn (mitosis)

Nguyn phn t n c th chia lm bn giai on khc nhau, din tin
theo mt trnh t nh sau: k trc (prophase), k gia (metaphase), k
sau (anaphase) v k cui (telophase). Mi giai on c mt nt c trng
ring, c bit l mi lin quan vi tp tnh ca nhim sc th, nh m
ta c th xc nh chng (hnh 3.8 v 3.9).
Sau khi t nhn i k trung gian (c th l pha S) v hon tt vic
chun b bc vo nguyn phn (pha G2), lc ny cc nhim sc th tip
tc ng xon v kt c, nh vy chng hin r dn di knh hin vi
quang hc. Mi nhim sc th by gi gm hai chromatid ch em (sister
77
chromatids) dnh nhau tm ng. Theo nguyn tc, cc chromatid ny

hon ton ging nhau do kt qu ca s ti bn bn bo ton DNA pha S
(chng 5). Hn na, v hai chromatid ch em dnh nhau ti vng tm
ng, nn chng c xem l mt nhim sc th.
Hnh 3.9 Cc giai on ca qu trnh nguyn phn mt t bo chp r

hnh ty (Allium cepa).
2.1. K trc (prophase)

Cng trong giai on ny, hch nhn (nucleolus) thng bin mt v
mng nhn bt u tan v. Trung th (centriole) phn chia v hnh thnh
xung quanh n mt cu trc mi gm rt nhiu si thoi (spindle fiber) tri
di ti cc cc ca t bo. Mt s si thoi nh trc tip vo tm ng (c
th l kinetochore) ca nhim sc th.
2.2. K gia (metaphase)
Vo k gia, mng nhn tan bin hon ton, cc si thoi nh vo tm
ng ca cc nhim sc th v y chng v mt phng xch o
(equatorial plane) ca t bo v xp thnh mt vng. Ni chung, lc ny
cc nhim sc th ng xon cc i (ngha l chiu di rt ngn ti a v
do ng knh cng n ra ti a), vi cu trc in hnh c trng cho
tng loi. Do , k gia l thi im thun li nht cho vic thit lp cc
kiu nhn v nghin cu hnh thi hc cc nhim sc th nh ni trn.
2.3. K sau (anaphase)
Vo u k sau, ti mi nhim sc th xy ra s phn tch tm ng,
cc chromatid ch em by gi ri nhau v c gi l cc nhim sc th
con (daughter chromosomes). K , cc si thoi co rt v gy ra s
chuyn ng ca cc nhim sc th con ging nhau v hai cc i din.
Nu nhn di knh hin vi lc ny, ta thy nhim sc th xut hin di
78
dng ch V, J hoc I, ty theo kiu tm gia, tm u hay tm mt.

Nh vy, chnh s sp xp thnh mt vng ca cc nhim sc th k
gia v s phn ly ng u ca chng v hai cc k sau lm thnh bn
cht hay l quy lut c trng cho qu trnh nguyn phn.
2.4. K cui (telophase)
Vo k cui, hai b nhim sc th con v ti cc cc i din v bt
u m xon. Lc ny mng nhn xut hin tr li v bao bc cc b
nhim sc th; cc si thoi tan bin, hch nhn v cc nhn c hnh
thnh tr li.
K , ng vt, mng t bo hnh thnh mt eo tht (furrow) t
ngoi vo trong; thc vt, mt phin t bo (cell plate) pht trin t
trung tm ra ngoi. iu ny lm phn cch hai b nhim sc th con v t
bo cht gia hai t bo con. Cc t bo con c s lng nhim sc th
ging vi t bo ban u. Nh vy, thc ra, nguyn phn gm hai qu
trnh phn chia: phn chia nhn (karyokinesis) v phn chia t bo cht
(cytokinesis); nhng thc cht ca nguyn phn l s phn chia nhn.
IV. Gim phn, s pht sinh giao t v th tinh

1. Gim phn (meiosis)
Gim phn l kiu phn bo c trng cho cc t bo sinh dc, trong
cc t bo con sinh ra (gi chung l cc giao t) c s lng nhim sc
th gim i mt na (hnh 3.10).
(3) gim phn II
(2) gim phn I
(1) k trung gian
cp nhim sc th
tng ng
Hnh 3.10 Kt qu ca gim phn vi hai ln phn chia. y cho thy

hu qu ca s ti t hp v phn chia gim nhim trong gim phn I.
Gim phn l mt giai on trong qu trnh pht sinh giao t, xy ra

pha trng thnh (mature) sau khi b nhim sc th c nhn i k
trung gian thuc pha sinh trng. Qu trnh gim phn gm hai ln phn
79
chia ni tip nhau, gim phn I v gim phn II (hnh 3.10). Mi ln phn
chia ny cng c chia lm bn k. Gim phn I (meiosis I) cn gi l
phn chia gim nhim (reductional division), v s lng nhim sc th
(2n) gim xung cn n bi (n). Trong gim phn I, cc chromatid ch
em vn cn dnh nhau trong khi cc nhim sc th tng ng phn ly.
Gim phn II (meiosis II) cn gi l phn chia ng u (equational
division) v rt ging vi nguyn phn ch phn tch cc chromatid ch
em v s lng nhim sc th gi nguyn khng i.
Bi v gim phn l qu trnh di truyn quan trng v cn bn nht
cp t bo, c s cho vic l gii cc quy lut di truyn v bin d, cho
nn trc khi i vo m t gim phn, cn nm ba im chnh sau y: (1)
Gim phn cng vi s th tinh sau cho php duy tr s lng nhim
sc th cc loi sinh sn hu tnh. (2) Gim phn I cho php cc nhim
sc th b v m khc nhau phn ly ngu nhin v mi giao t. (3) S trao
i cho gia cc chromatid trn cc cp nhim sc th tng ng k
trc trong gim phn I to ra cc t hp allele mi cc gene khc nhau.
1.1. Gim phn I (meiosis I)
1.1.1. K trc I (prophase I)
y l pha phc tp nht ca ton b qu trnh gim phn, c chia
lthnh nm giai on khc nhau (hnh 3.11a-e). Giai on th nht gi l
giai on leptotene (si mnh), c trng bng s xut hin ca cc nhim
sc th dng cc si mnh khi nhn di knh hin vi quang hc.
K tip l giai on zygotene (si kt hp), cc nhim sc th tng
ng tin li gn nhau v cc gene tng ng i din nhau. Qu trnh kt
hp ca cc nhim sc th tng ng sau gi l tip hp (synapsis), l
nt c trng c bn phn bit gia gim phn v nguyn phn. Cu trc
gm hai nhim sc th tng ng cha bn chromatid kt cp nh vy
gi l th lng tr (bivalent).
Giai on th ba c tn l pachytene (si dy), v lc ny cc th
lng tr ngn li v dy ln v s tip hp hon tt. Trong giai on ny
c th xy ra hin tng trao i cho (crossing over) hay ti t hp
(recombination) tng phn ca mi cp nhim sc th tng ng.
Giai on th t gi l diplotene (si kp), cc nhim sc th tng
ng bt u tch ra, c bit l cc vng nm hai bn tm ng. (D
nhin, cc chromatid ch em cn dnh nhau tm ng cho ti u k sau
II). Thng thng mi cp nhim sc th tng ng c th c mt hoc
hai vng trong chng vn cn k st nhau hoc tip xc vi nhau, gi l
cc hnh cho (chiasmata). Cc hnh cho ny (hnh 3.12) l bng chng
80
vt l cho s ti t hp xy ra sau khi cc nhim sc th tng ng

tip hp. Ni chung, c t nht mt hnh cho trn mt vai nhim sc th,
nhng dc theo cc nhim sc th th c th c mt s hnh cho.
Giai on cui ca k trc I, diakinesis, c c trng bng s ngn
li ca cc nhim sc th v chm dt cc hnh cho. iu c ngha l,
cc hnh cho b y v cc u mt ca cc nhim sc th. Lc ny, hch
nhn v mng nhn cng bin mt.
Hnh 3.11 Cc giai on ca qu trnh gim phn hoa hnh ty (Allium

cepa). K trc I gm 5 giai on: (a) leptotene, (b) zygotene, (c) pachytene,
(d) diplotene, v (e) diakinesis. Tip theo l (f) k gia I, (g) k sau I, (h) k
cui I, (i) k ngh ngn gia hai ln phn chia (interkinesis), (k) k gia II,
(l) k sau II, v (m) k cui II.
1.1.2. K gia I (metaphase I)

k gia I (hnh 3.11f), cc nhim sc th xp trn mt phng xch
o thnh hai vng v cc tm ng c nh vo cc si thoi, sao cho c
hai nhim sc th ca mi cp tng ng (tc th lng tr) nm i din
nhau qua mt phng k gia, vi cc hnh cho xp thng hng dc theo
n. S kin ny khc bit vi k gia nguyn phn v l c s cho s phn
chia gim nhim v phn ly ngu nhin ca cc nhim sc th k sau I.
1.1.3. K sau I (anaphase I)
Vo lc ny, hai tm ng trong cc nhim sc th tng ng ca
81
mi th lng tr y nhau ra xa, sao cho mt nhim sc th ca mi cp

tng ng i v mt cc (hnh 3.11g). Khi cc nhim sc th tng ng
y nhau ra, cc hnh cho hon ton chm dt. Khc vi k sau nguyn
phn, cc chromatid ch em k sau I vn cn dnh nhau tm ng.
(a)
(b)
Hnh 3.12 (a) Cc hnh cho trn mt cp nhim sc th. (b) S hnh thnh
cc chromatid ti t hp bi mt hnh cho t hai nhim sc th tng ng.
1.1.4. K cui I (telophase I)

hu ht sinh vt, sau khi cc nhim sc th di chuyn ti cc cc th
mng nhn hnh thnh xung quanh chng v t bo ny phn chia thnh
hai t bo con (hnh 3.11h). Tuy nhin, cc chi tit chnh xc v mt t bo
hc ca k cui I cn nhiu sai bit, c bit l cc thc vt.
1.2. Gim phn II (meiosis II)
Gia gim phn I v gim phn II thng ch c mt k trung gian
ngn ngi gi l interkinesis (hnh 3.11i) Trong thi gian ny khng xy ra
s tng hp DNA; mi t bo cha mt b nhim sc th n bi (n),
trong mi nhim sc th cha hai chromatid ch em. K trc II
(prophase II) thng xy ra rt nhanh v khng r nt; cc k cn li
tng t nh trong nguyn phn. Tht vy, k gia II (metaphase II),
cc tm ng nh vo cc si thoi v di chuyn v mt phng xch o
(hnh 3.11k). Vo u k sau II (anaphase II), cc nhim sc th tch nhau
tm ng v sau cc nhim sc th con phn ly v cc cc i din
(hnh 3.11l). K cui II (telophase II) bt u khi ti mi cc c mt b
nhim sc th n bi n (n) v mng nhn hnh thnh xung quanh chng
(hnh 3.11m).
Nh vy, theo nguyn tc, t mt t bo sinh dc 2n tri qua gim
phn cho ra bn t bo sinh dc n bi, gi l cc giao t (hnh 3.10).
2. S pht sinh giao t (gametogenesis)
Nh bit, gim phn l thi k hay pha (phase) quan trng nht ca
qu trnh pht sinh giao t ng vt v pht sinh bo t thc vt. Di
y ch cp ch yu qu trnh pht sinh giao t ng vt (hnh 3.13).
ng vt, s to thnh cc giao t c hay tinh trng (sperm), gi l
s sinh tinh (spermatogenesis), xy ra trong tinh hon (teste) - c quan
82
sinh sn c. Qu trnh ny bt u vi s sinh trng ca mt t bo

lng bi cha bit ha gi l t bo m tinh trng (spermatogonium). Ti
pha sinh sn, t bo ny thc hin nhiu ln qu trnh nguyn phn gia
tng s lng t bo m tinh trng (2n). Sau , mi t bo ny chuyn
qua pha sinh trng, bit ha thnh mt tinh bo s cp (primary
spermatocyte; 2n kp). K , t bo ny tri qua pha trng thnh vi hai
ln phn chia lin tip ca gim phn. Sau gim phn I, mt tinh bo s
cp cho ra hai tinh bo th cp n bi kp (secondary spermatocyte; n
kp). Sau gim phn II, mi t bo ny phn chia thnh hai tinh t n bi
(spermatid; n). Bc cui cng l s bit ha ca cc tinh t thnh cc t
bo tinh trng (sperm), c cu to y cc b phn (nh u, c v
ui di; hnh 3.13 v 3.14).
Hnh 3.13 S minh ha qu trnh sinh tinh v sinh trng ng vt.
S sinh trng (oogenesis) hay to cc giao t ci ng vt xy ra
83
trong cc bung trng (ovary), c quan sinh sn ci. Qu trnh ny cng

bt u bng mt t bo m ca trng (oogonium; 2n). Sau khi tri qua
pha sinh sn, mi t bo sinh non ny bit ha thnh non bo s cp
(primary oocyte; 2n kp) pha sinh trng, vi kch thc tng trng
mt cch c bit. Ti pha trng thnh, sau gim phn I, t non bo s
cp to ra mt non bo th cp (secondary oocyte; n kp) v th cc
(polar body) th nht. Sau ln gim phn II, t non bo th cp cho ra
mt non t (ootid; n) v mt th cc, cn th cc kia to ra hai th cc
th hai. Chung cuc, t mt t bo sinh non (2n) cho ra ch mt non (n)
kch thc rt ln v ba th cc (n) kch thc rt nh. Nguyn nhn l do
gim phn xy ra gn mng t bo, nn cc th cc ch nhn c mt t t
bo cht v chng vn cn bm trn b mt ca trng cho n lc tiu
bin, tch ra. S tp trung t bo cht trong mt non t ri sau bit
ha thnh trng (ovum, egg) chnh l ngun cung cp cht dinh dng cho
s pht trin phi sau khi th tinh.
S sinh tinh din ra lin tc cc ng vt trng thnh sinh sn
quanh nm, chng hn nh ngi v ty theo ma cc ng vt sinh sn
theo ma. Kh nng cho tinh trng l cc k cao hu ht cc ng vt;
mt con c (male) trng thnh sn xut hng t t tinh trng trong sut
qung i ca chng. Ngc li, vic sinh trng cc con ci (female) ni
chung l thp hn rt nhiu; chng hn, mt ngi n sut i ch c th
sn sinh chng 500 trng chn. Tt c s trng ny pht trin thnh cc
non bo s cp trc khi con ci (female) c sinh ra v chng dng li
k trc I cho ti tui dy th. Lc ny chng tip tc gim phn v bt
u chn ln lt thnh cc trng v mi thng rng mt trng. T bo
trng ngi c ng knh chng 0,1 mm (100 m) trong khi phn
rng nht ca tinh trng c ng knh l 2,5 m.
thc vt bc cao, s hnh thnh cc giao t c c gi l s hnh
thnh ht phn hay pht sinh tiu bo t (microsporogenesis). Qu trnh
ny ging nh s sinh tinh ng vt ch gim phn cho ra bn t bo
n bi c cng kch thc v tim nng chc nng. S hnh thnh non
thc vt cn gi l s hnh thnh ti phi hay pht sinh i bo t
(megasporogenesis). N cng tng t nh qu trnh gim phn ng
vt. Tuy nhin, cc sn phm sai khc nhau ng k.
3. S th tinh (fertilization)
Ni chung, th tinh (hnh 3.14) l hin tng kt hp ngu nhin gia
cc giao t c v giao t ci mang b nhim sc th n bi (n) to thnh
cc hp t (zygotes) c b nhim sc th lng bi (2n) c trng ca
loi. Thng thng, mt trng ch c th tinh bi mt tinh trng v to
84
ra mt hp t (hnh 3.14b).
cc thc vt bc cao c qu trnh th tinh kp (double fertilization).
Khi ng phn xm nhp ti phi (embryo sac) v a hai tinh t vo, s
xy ra hai qu trnh th tinh: mt tinh t s kt hp vi non (egg) to
thnh hp t (2n) v tinh t kia s dung hp vi nhn ni nh (endosperm
nucleus; 2n) to thnh mt nhn ni nh (3n). Sau , trong qu trnh hnh
thnh ht, hp t s pht trin thnh phi ht v nhn ni nh s pht trin
thnh ni nh nui phi, gi l phi nh.
(a)
(b)
Hnh 3.14 (a) Cc tinh trng nhm bin (sea urchin) vy quanh mt trng
nhm bin. (b) Mt t bo trng ngi va c th tinh, cc nhn ca tinh
trng v trng th hin bng hai hnh dng khng u nhau, c mu vngnu. Khi hai nhn ny dung hp th s th tinh coi nh hon tt.
Ngun: (a) Francis Leroy, Biocosmos/SPL/Photo Researchers, Inc.
(b) Phototake NYC/Dr. Nikas/Jason Burns 1993-2003 Microsoft Corporation.
V. Cc bin i ca nhim sc th
Trn y chng ta mi ch tm hiu cc c tnh di truyn n nh ca
nhng c th mang b nhim sc th bnh thng m cha cp n mt
bin i ca n. Trn thc t, cc nhim sc th c th b bin i (t
bin) theo hai cch cn bn, l cc bin i v cu trc v v s lng
(bng 3.2). Cc bin i ny c th gy nhng hu qu khc nhau ty loi,
nhng thng l nghim trng. Chng c th gy hiu qu tc thi ln cc
nhim sc th, gy ri lon trong hot ng ca b gene v gim phn; v
t nh hng ti sc sng, hu th...ca cc c th mang chng.
1. Cc bin i v cu trc nhim sc th
C bn kiu bin i cu trc nhim sc th, l: lp on (hay nhn
on), mt an (hay khuyt an), o on v chuyn on nh gii
thiu bng 3.2 (xem Hnh 3.15). Cc kiu t bin cu trc nhim sc
th xy ra l do s t gy v ni li bt thng ca cc on trn cng
mt cp tng ng hoc thm ch gia cc cp khc nhau nh trong
trng hp chuyn on. Ni chung, cc t bin ny thng t gp, trung
85
bnh c 1.000 giao t mi hnh thnh c mt vi t bin lin quan kiu

no . Cc hu qu v sau u l kt qu ca s tip hp gene-i-gene
gia cc nhim sc th bnh thng v bt thng (kiu kt cp khng
hon ton tng xng ny c gi l kiu d nhn, heterokaryotypic)
cng nh cc vn sau ny xy ra cc k sau I v II trong gim phn.
Bng 3.2 Cc kiu bin i (t bin) nhim sc th
Cc kiu bin i v cu trc
Lp on (duplication)
Mt on (deletion)
o an (inversion)
Chuyn on (translocation)
Cc kiu bin i v s lng

Mc nguyn bi (Euploidy)
Cc th t a bi (autopolyploids)
Cc th d a bi (allopolyloids)
Lch bi (Aneuploidy)
Cc th mt (monosomies; 2n 1)
Cc th ba (trisomies; 2n + 1)
1.1. Lp on (duplication)
Lp on hay nhn on l
trng hp mt on nhim sc th no
c mt hai ln trn mt nhim sc th.
Ty theo v tr v trt t ca cc vng
lp an, ta c th phn ra hai kiu chnh
sau: (i) Lp on c th nm k st vng
nhim sc th ban u. Trong trng
hp trt t cc bng (hoc cc gene) vn
gi nguyn nh ban u th gi l lp
an ni tip (tandem), hoc c trt t
ngc li, gi l lp an o ngc
(reverse). (ii) Nu nh vng lp li nm
cch xa on gc ban u th gi l lp
on chuyn ch (displaced).
C th hnh dung cch lp on ni
tip xy ra l do cc nhim sc th tng
ng gi nhau v c cc ch t ng
thi trn hai nhim sc th ti cc im
khc nhau. Nu cc nhim sc th tng
ng khc nhau ny ni li, th mt
chic s c mt on lp ni tip v
chic kia s mt i mt on tng ng.
Mt on
Lp on
o on
Xen on
Chuyn on
Hnh 3.15 S tng qut cc kiu bin i cu trc nhim sc th.

Kiu xen on y l s chuyn an gia (interstitial translocation).
86
Trong trng hp , lp on v mt on l hai kiu thun nghch

ca nhau. iu cng c th do c ch trao i cho khng u (unequal
crossing over) gy ra (Hnh 3.16).
Hnh 3.16 Lp on v mt on do c ch trao i cho khng u gy ra.
Hu qu l:
(1) V phng din t bo hc, khi mt c th l d hp kiu nhn v
mt nhim sc th lp on v mt nhim sc th bnh thng th vng lp
on khng c on tng ng kt cp trong gim phn. Lc
on lp s phnh ra di dng mt cu trc hnh vng (loop) sao cho cc
phn cn li ca c hai nhim sc th c th bt cp vi nhau, tc tip hp
gene-i-gene (Hnh 3.17). mt s trng hp, mt vai nhim sc th c
cha on lp c th un vng li sao cho hai u ca on lp giao nhau.
Hnh 3.17 S kt cp ca cc nhim sc th cc c th c kiu nhn d

hp v (a) lp on ni tip - tandem v (b) lp on o ngc - reverse.
(2) V phng din kiu hnh, cc c th d hp hoc ng hp v cc

on lp b vn c th sng, mc d chng thng bc l ra mt vi hiu
qu kiu hnh (nh trong trng hp cc t bin mt Bar rui gim).
(3) V phng din tin ha, nu nh cc c th mang cc t bin ny
vn sng bnh thng, th chng s c tim nng cho s bin i tin ha
xa hn na cc gene ph thm ny, gi l tin ha bng c ch nhn i
gene. Thc ra, c rt nhiu bng chng chng t s nhn i gene l mt
87
c ch quan trng nht sinh ra cc gen mi v cc qu trnh tin ha

mi, to thun li cho s tin ha ca cc sinh vt phc tp t cc sinh vt
nguyn s. Chng hn, cc gene khc nhau m ha cho hemoglobin cc
ng vt c xng sng c th bt ngun t mt gene t tin c nhn
i, v sau cc bn sao nhn i ny phn ly v mt chc nng ca
chng (c th xem thm trong: Kimura 1983; Li 1983).
1.2. Mt on (deletion)
Mt nhim sc th b khuyt mt i mt an c gi l t bin mt
an (deletion) hay khuyt on (deficiency) (hnh 3.18). Mt on c th
xy ra ti mt phn bn trong nhim sc th, gi l mt on gia hay mt
an khe (interstitial deletion). Cn nu nh mt an nhim sc th b
t v khng ni li c, gi l mt on mt (terminal deletion). Trong
trng hp on t gy c cha tm ng th c on ny ln nhim sc
th mt an thng s b dung gii trong qu trnh phn bo. C ch mt
on do s trao i cho khng u ni ti phn trn.
(a)
(b)
Hnh 3.18 (a) C ch gy mt on mt (tri) v on khe; (b) Hi chng

cri du chat do mt on mt trn vai ngn nhim sc th s 5.
Hu qu: Khi cc th mt an trng thi ng hp, chng thng b

cht do khuyt hn cc gene thit yu. Thm ch khi trng thi d hp,
cc gene gy cht c th gy ra s pht trin bt thng. Mt v d ni
ting ngi l t bin mt on mt phn ng k ca vai ngn
trn nhim sc th s 5 (5p), khi trng thi d hp gy ra hi chng "mo
ku" (ting Php: cri du chat; ting Anh: cry-of-the-cat). Nhng a tr
mc hi chng ny ni chung c ging cao the th c trng ging nh
ting mo ku, c u nh v tr n; v chng thng b cht sm
tui s sinh hoc th u (Hnh 3.18).
Ngoi ra, cc th d hp v mt an thng cho thy s kt cp
nhim sc th bt thng trong gim phn. Do n khng c vng tng
ng m kt cp vi, nn trn nhim sc th bnh thng s hnh thnh
mt ci vng gi l vng mt on (deletion loop).
Tuy nhin, mt s c im khc li t ra hu ch cho vic xc nh
cc mt an, chng hn: (1) Khng nh cc t bin khc, cc t bin
88
mt an l khng o ngc tr thnh nhim sc th kiu di c (tc

dng bnh thng vn c ca t nhin). (2) cc th d hp mt on, cc
allele ln trn nhim sc th bnh thng s biu hin ra kiu hnh bi v
nhim sc th mt on b khuyt vng tng ng. S biu hin ca cc
allele ln trong trng hp nh vy, gi l hin tng tri gi (pseudodominance); n c ch trong vic xc nh chiu di ca on b mt.
1.3. o on (inversion)
o an l hin tng xy ra do s t ng thi ti hai im trn
mt nhim sc th v sau on b t xoay 180o ri ni li. Hu qu l,
trt t cc gene trong on o ngc li vi trt t bnh thng (hnh
3.15). Ty theo s tng quan ca on o vi v tr tm ng, c th
chia lm hai kiu o an. Nu an o khng cha tm ng, gi l
o on cn tm (paracentric inversion); ngc li, nu on o bng
qua c tm ng th gi l o on quanh tm (pericentric inversion).
Hnh 3.19 S trao i cho xy ra bn trong vng ca th d hp o on

cn tm to ra cc giao t cha cc khuyt an ln. (a) Kt cp v xut hin
vng; (b) Phn ly lm xut hin cu ni v on khng tm; (c) Cu ni hai tm
t gy ngu nhin; v (d) Cc sn phm c to ra.
89
V c ch, c th hnh dung nh sau: v l do no , mt nhim sc

th xon li mt vai (khng lin quan tm ng) hoc bng qua c hai
vai (tm ng nm trn vng cun), sau xy ra s t gy ti vng giao
nhau ri ni li khng ng. Cc c th d hp v mt on o c th
nhn din bi s c mt ca cc vng o on (inversion loops) trn cc
nhim sc th thuc giai an si dy (pachytene) ca gim phn. l
do i lc ca hai nhim sc th tng ng. Cch duy nht m hai nhim
sc th tng ng ny cp c vi nhau l mt chic t n xon li
thnh mt cu trc hnh vng trong khi chic kia lm thnh mt na vng
bao quanh n m khng xon li. Nu nh s trao i cho xy ra trong
vng c on o (Hnh 3.19), c th dn ti hnh thnh cc giao t cha
cc on lp v khuyt an ln v thng gy cht giai an hp t.
1.4. Chuyn on (translocation)
Chuyn an l di chuyn ca mt on nhim sc th t mt nhim
sc th ny sang mt nhim sc th khc, khng tng ng vi n v gy
ra s cu trc li nhim sc th ng k (hnh 3.15, 3.20). C hai kiu
chuyn an: (i) chuyn on gia (interstitial translocation) l s di
chuyn mt on cho mt nhim sc th khc m khng nhn li, tc
chuyn on khng thun nghch; v (ii) chuyn on thun nghch
(reciprocal translocation), tc c s trao i qua li hai chiu. Kiu th hai
ph bin hn. Nu nh hai on c ni li trong chuyn an thun
nghch to ra hai chic c kch thc ln v hai chic kia b, th cc nhim
sc th c chuyn on c kch thc b hn thng b bin mt. Khi
, s lng nhim sc th b gim i do s trao i nhim sc th. Nh
th, cc chuyn an c th lm thay i c kch thc ln v tr tm ng.
Nhng c th d hp v chuyn on ch sinh ra khong mt na s
con bnh thng; hin tng c gi l bn bt dc (semi-sterility).
Khi cc th d hp chuyn on tri qua gim phn s cho ra khong mt
na s giao t cha c hai phn ca chuyn on thun nghch v khong
mt na kia cha c hai nhim sc th bnh thng. S giao t cn li ch
cha mt phn ca chuyn an v mt nhim sc th bnh thng; cc
giao t loi ny s gy cht hp t do mt cn bng v vt cht di truyn.
in hnh l trng hp chuyn an Robertson (Robertsonian
translocation), trong cc vai di ca hai nhim sc th tm u khng
tng ng gn vi nhau v ch c mt tm ng (hnh 3.20b). Cn nhim
sc th tm u b t gy vai di v on t t nhim sc th kia c
ni li thng bin mt trong qu trnh phn bo hoc sau vi th h. Cc
chuyn an Robertson c ngha quan trng trong di truyn hc ngi.
90
(a)
(b)
NST 14
NST 21
NST (14 + 21q)
Hnh 3.20 (a) Chuyn on thun nghch; (b) Chuyn on Robertson, v

s bn di cho thy s t - ni ca hai nhim sc th khng tng
ng to ra kiu chuyn on ny. Mi tn () ch cc im t.
Mc d cc chuyn an c th to ra cc nhim sc th bnh thng,

song chng cng c th gy ra nhiu bnh di truyn ngi. Chng hn,
khong 5% s ngi mc hi chng Down (Down syndrome) c mt b
m l d hp v mt chuyn an. C th trong trng hp ny, vai di
nhim sc th 21 (an 21q) b t ra v gn vo ch t trn vai ngn
nhim sc th 14; ngi b hoc m ny trng thi d hp vi kiu hnh
bnh thng, nhng c nguy c gy hi chng Down i con do s phn
ly sai hnh xy ra trong gim phn. Theo nguyn tc, khi gim phn, th d
hp chuyn on c th to ra bn loi giao t, vi xc sut ngang nhau,
thuc hai nhm c b nhim sc th cn bng v khng cn bng sau y:
[14 ; 21] : [14 + 21q] : [14] : [(14 + 21q) ; 21]
Khi cc giao t ny th tinh vi cc giao t bnh thng [14 ; 21] s cho
ra bn kiu hp t tng ng l:
[(14)2 ; (21)2] : [(14;14 + 21q) + 21] : [(14)2 + 21] : [(14;14 + 21q) + (21)2]
Bnh thng : Th d hp chuyn an : Th mt 21 : Th ba 21
(46)
(45)
(45; cht)
(46)
Bi v cc c th nhn c ch mt nhim sc th 21 s b cht, nn
chung cuc c khong 1/3 s tr sng (t mt th d hp chuyn on nh
vy) c k vng l mc hi chng Down. Trn thc t, t l ny thp
hn 1/3, ch yu l do mt s c th khng sng st c thi k thai.
Cn lu rng, nguyn nhn ny ca hi chng Down a ra cc gi
cho t vn di truyn (genetic counseling) ch: (1) Hi chng Down c
th ti din cc con ci ca mt kiu nhn d hp v chuyn on, trong
91
khi hi chng Down bnh thng th khng ti din trong cc anh ch

em rut v v sinh (xem mc 2.2 di y). (2) Mt na s anh ch em
rut bnh thng v kiu hnh ca cc c th Down chnh h li l nhng
th d hp v chuyn an, v do c th sinh ra con ci b Down.
nc ta, theo Nguyn Vn Rc (2004), c khong 6% trng hp
hi chng Down do cc th chuyn on gy ra, bao gm cc dng t(14q;
21q), t(21q; 21q) v t(21q; 22q).
Trn hnh 3.21 trnh by c ch hnh thnh cc loi giao t t ngi n
thuc dng chuyn on t(21q; 22q) v s th tinh gia mt trng bt
thng c nhim sc th 22 c chuyn on 21q (k hiu l:
23,X,+21q) vi tinh trng bnh thng (23,X) to ra hi chng Down
thuc dng chuyn on (46,XX, +21q).
(a)
(b)
Hnh 3.21 Hi chng Down do th chuyn on dng t(21q; 22q) gy ra:
(a) S hnh thnh cc loi giao t khc nhau t ngi n t(21q; 22q); v (b) S
th tinh gia mt trng bt thng (23,X,+21q) vi tinh trng bnh thng
(23,X) to ra hi chng Down chuyn on dng (46,XX, +21q).
2. Cc bin i v s lng nhim sc th

T bng 3.2 cho thy s bin i s lng nhim sc th sai khc nhau
hai cch c bn: (1) Cc th bin d nguyn bi hay th a bi (euploid
variants) c s lng cc b nhim sc th khc nhau; v (2) cc th bin
d lch bi hay th d bi (aneuploid variants) c s lng nhim sc th
c th khng phi l lng bi. Ni chung, cc kiu bin i s lng
nhim sc th nh hng ln s sng st ln hn cc kiu bin i cu
trc nhim sc th. Trn thc t, ngi, hn mt na cc trng hp sy
thai t nhin xy ra trong ba thng mang thai u c lin quan ti cc thai
b lch bi, a bi, hoc cc sai hnh nhim sc th ln khc.
Trc khi tho lun cc th t bin s lng nhim sc th lin quan
ti s tng hoc gim hm lng vt cht di truyn, ta hy xt qua cc c
ch khc m qua s lng nhim sc th c th thay i (hnh 3.22).
92
(a)
NST 1
(b)
NST 2
NST ln (1q + 2q)
+
NST b
(c)
Hnh 3.22 S hnh thnh nhim sc th tm gia do dung hp tm ng

ca hai nhim sc th tm u khng tng ng (a), v cc dng nhim sc
th hai tm v khng tm (b v c).
Nh cp, nu nh cc chuyn an thun nghch xy ra gia hai

nhim sc th tm u m cc an ln (tc vai di) c ni li vi nhau,
kt qa l to ra mt nhim sc th ln c tm gia v mt nhim sc th
b m n c th bin mt trong qu trnh phn bo. C ch hnh thnh mt
nhim sc th tm gia ln do s t-ni xy ra ti cc tm ng ca hai
nhim sc th tm u khng tng ng nh th gi l s dung hp tm
ng (centric fusion; hnh 3.22a). Ngoi ra, thnh thong cng bt gp cc
dng nhim sc th bt thng c hai tm ng v khng tm ng (hnh
3.22b-c). Tuy nhin, cc dng bt thng nh th c tnh khng n nh
bi v chng thng b loi b khi t bo khi phn ly v hai cc trong qu
trnh phn bo; chng hn, dng hai tm ng thng xut hin dng cu
ni v s b t gy do cc si thoi ko cng v hai cc.
2.1. Hin tng a bi (polyploidy)
Cc th a bi (polyploids) l
trng hp trtong cc sinh vt c
ba, b nhim sc th tr ln (hnh
3.23). Nu ta gi x l s nhim sc
th n bi c bn, khi cc sinh
vt c ba, bn b nhim sc th... s
c s nhim sc th v tn gi tng
ng l 3x (th tam bi: triploid), 4x
(th t bi: tetraploid)... Lu : thay
v dng k hiu n ch s nhim
sc th n bi nh trc y, y
x ch s nhim sc th trong mt b
v n biu th cho s nhim sc th
trong mt giao t. V d: mt sinh
vt lc bi vi 60 nhim sc th (6x
= 2n = 60), th x = 10 v n = 30.
Hnh 3.23 Hin tng a bi ha in hnh chi Chrysanthemum, vi
rt nhiu loi a bi th khc nhau sinh ra t loi lng bi (2n = 18).
93
Ni chung, hin tng a bi th tng i ph bin cc thc vt

nhng him gp hu ht cc ng vt. Gn nh mt na s thc vt c
hoa u l cc th a bi, k c cc loi cy trng quan trng. Chng hn,
khoai ty t bi (4x = 48), la m mm lc bi (6x = 42), v cy du ty
bt bi (8x = 56). thc vt bc cao, Chrysanthemum l mt chi in
hnh v hin tng a bi ha (hnh 3.23). Trong qu trnh gim phn
cc loi thuc chi ny, cc nhim sc th kt i to thnh cc th lng
tr, loi 118 nhim sc th to thnh 9 th lng tr, loi 36 nhim sc th
to thnh 18 th lng tr v.v... Mi giao t nhn mt nhim sc th t mi
th lng tr, v vy s lng nhim sc th trong mi giao t ca bt k
loi no cng chnh bng mt na s lng nhim sc th c tm thy
trong mi t bo soma ca n. V d, loi thp bi c 90 nhim sc th th
to thnh 45 th lng tr, do mi giao t s mang 45 nhim sc th.
Nh vy qua th tinh, b y 90 nhim sc th ca loi ny c phc
hi. Nh vy, cc giao t ca c th a bi r rng l khng phi n bi
nh c th lng bi.
Thng thng, ngi ta phn bit hai kiu th a bi: (1) cc th a
bi cng ngun hay th t a bi (autopolyploids) l cc th a bi nhn
c tt c cc b nhim sc th ca chng t cng mt loi; v (2) cc
th a bi khc ngun hay th d a bi (allopolyploids) l cc th a bi
nhn c cc b nhim sc th t cc loi khc nhau. Chng hn, nu
nh mt ht phn lng bi khng gim nhim t mt loi lng bi th
tinh cho mt trng lng bi cng ca loi , i con sinh ra l cc th t
t bi (autotetraploids), hay AAAA, trong A biu th mt b nhim sc
th hon chnh hay b gene (genome) ca kiu A. Mt khc, nu nh ht
phn lng bi ca mt loi th tinh cho mt trng lng bi ca mt loi
khc c quan h h hng vi loi ny, i con sinh ra s l cc th d t
bi (allotetraploids), hay AABB, trong B ch b gene ca loi th hai.
Tt c cc b nhim sc th trong mt th t a bi u l tng ng,
ging nh khi chng trong mt th lng bi. Nhng trong cc th d a
bi, cc b nhim sc th khc nhau ni chung sai khc nhau mt mc
no , v c gi l tng ng mt phn (homeologous), hay tng
ng tng phn (partially homologous).
Trong t nhin, cc th a bi xy ra vi tn s rt thp, khi mt t bo
tri qua s nguyn phn hoc gim phn bt thng. Chng hn, nu trong
nguyn phn tt c cc nhim sc th i v mt cc, th t bo s c s
nhim sc th l t t bi. Nu nh xy ra gim phn bt thng, c th
to ra mt giao t khng gim nhim c 2n nhim sc th. Tuy nhin,
trong hu ht cc tnh hung, giao t lng bi ny s kt hp vi mt
giao t n bi bnh thng v sinh ra mt th tam bi. Ngi ta cng c
94
th to ra cc th a bi bng cch x l colchicine, mt loi ha cht gy

ri lon s hnh thnh thoi v sc. Kt qu l, cc nhim sc th khng
phn ly v cc cc c, v thng th xut hin cc th t t bi.
2.1.1. Cc th t a bi (autopolyploids)
Cc c th tam bi (AAA) thng l cc th t a bi sinh ra do th
tinh gia cc giao t n bi v lng bi. Chng thng bt dc bi v
xc sut sinh ra cc giao t c c cn bng l rt thp. Trong gim phn,
ba ci tng ng c th kt cp v hnh thnh mt th lng tr, hoc hai
ci tng ng kt cp nh l mt th lng tr, li nhim sc th th
ba khng kt cp. Tuy nhin, do tp tnh ca cc nhim sc th khng
tng ng l c lp, nn xc sut mt giao t c chnh xc n nhim
sc th l ()n (s dng quy tc nhn), v xc sut mt giao t c c
chnh xc 2n nhim sc th cng l ()n. Tt c cc giao t khc cn li s
l khng c s cn bng v ni chung l khng hot ng chc nng trong
cc hp t c cha chng. Chng hn, hu ht cc cy chui l cc th tam
bi; chng sinh ra cc giao t khng cn bng, v kt qu l khng c ht.
Qu bnh
thng
Triticum kiu
di (2n = 14)
Triticum monococcum
(2n = 14)
Qu ca
th a bi
Con lai bt dc
Sai st do
gim phn
T. fauschii (kiu di)

(2n = 14)
T. turgidum
(2n = 28)
Hnh 3.24 S hnh thnh th a

bi vi hoa tri ln hn th 2n
bnh thng.
Hnh 3.25 S hnh thnh la m
Triticum aestivum d lc bi (2n = 42)
bng con ng d a bi.
Con lai bt dc
Sai st do
gim phn
T. aestivum
(2n = 42)
Cc th a bi thng ln hn cc th lng bi h hng (v d, cho

hoa tri ln hn; Hnh 3.24). Cc th t a bi c th gim phn bnh
95
thng nu nh chng ch to thnh cc th lng tr hoc cc th t tr.

Cn nu nh bn nhim sc th tng ng to thnh mt th tam tr v
mt th n tr, th cc giao t ni chung s c qu nhiu hoc qu t cc
nhim sc th.
2.1.2. Cc th d a bi (allopolyploids)
Hu ht cc th a bi trong t nhin u l cc th d a bi, v chng
c th cho ra mt loi mi. Chng hn, la m Triticum aestivum l mt
dng d lc bi vi 42 nhim sc th. Qua kim tra cc loi hoang di h
hng cho thy la m ny bt ngun t ba dng t tin lng bi khc
nhau, mi dng ng gp hai b nhim sc th ( y ta k hiu
AABBDD). S kt cp ch xy ra gia cc b nhim sc th tng ng,
v vy gim phn l bnh thng v cho ra cc giao t cn bng c n = 21.
R rng, hin tng d a bi ng vai tr quan trng trong s tin ho
ca la m (xem Hnh 3.25).
Nm 1928, nh khoa hc ngi Nga, G. Karpechenko to ra mt
th d t bi rt l c bit; khi ng lai gia ci bp Brassica v ci c
Raphanus sativus, c hai u c s nhim sc th lng bi l 18. ng
mun to ra con lai c l ca cy ci bp v c ca cy ci c. Sau khi thu
c cc ht lai t mt cy lai nhn to, em gieo trng v pht hin rng
chng c 36 nhim sc th. Tuy nhin, thay v thu c cc tnh trng nh
ng mong i, cy lai ny c l ca cy ci c v c ca cy ci bp! Hnh
3.26 cho thy s hnh thnh con lai gia hai loi ci c v ci bp ni trn,
c gi l Raphanobrassica.
Giao t
B m
Con lai F1 bt th
Th song nh bi hu th
Hnh 3.26 S to thnh th song nh bi hu th Raphanobrassica t hai

loi ci bp Brassica v ci c Raphanus u c 2n = 18 (tri); v mt kt
qu c th ca con lai F1 Raphanobrassica (theo W.P.Amstrong 2000).
96
Trong trng hp nu mt ht phn n bi c b gene A th phn

cho hoa ca loi c b gene B, s cho ra mt con lai bt th c thnh phn
b gene AB. Nu nh sau nguyn phn khng xy ra c trn mt
nhnh, c th sinh ra cc t bo AABB. Nu cc t bo ny t th phn th
s to ra mt th d a bi. Li dng c im ny, cc nh chn ging s
dng colchicine tc ng ln con lai bt th to ra cc th d a bi.
2.2. Hin tng lch bi (aneuploidy)
Trong t nhin, thnh thong ta bt gp cc c th c s lng nhim
sc th khng phi l bi s ca s nhim sc th n bi, do chng b
tha hoc thiu mt hoc vi nhim sc th c th no . l cc th
lch bi hay th d bi (aneuploids).
Gim phn I
Gim
phn II
Hnh 3.27 S khng phn tch xy ra trong gim phn I (bn tri) v gim
phn II (bn phi) vi cc giao t c to ra.
Nguyn nhn ca hin tng lch bi l s khng phn tch

(nondisjunction) ca hai nhim sc th tng ng trong qu trnh gim
phn hoc nguyn phn. S khng phn tch trong gim phn t n c
coi l kt qu ca s kt cp khng ng cch ca cc nhim sc th tng
ng trong gim phn sm n ni cc tm ng khng i din nhau trn
mt phng k gia, hoc l khng hnh thnh c hnh cho. Kt qu l
c hai nhim sc th cng i v mt cc, lm cho mt t bo con tha mt
nhim sc th v t bo con kia khng c nhim sc th . Khi cc giao
t bt thng (n + 1) v (n 1) ny th tinh vi cc giao t bnh thng
(n) s sinh ra cc hp t c b nhim sc th bt thng tng ng: tha
mt chic (2n + 1), gi l th ba (trisomy) v thiu mt chic (2n 1), gi
l th mt (monosomy). S khng phn tch ph bin nht l trong gim
phn I, nhng cng c th xy ra c trong gim phn II (hnh 3.27). Cc
97
kiu t hp nhim sc th khc nh 2n + 2 (th bn: tetrasomy) hoc 2n

2 (th khng: nullisomy) cng c th xy ra, nhng y ta khng quan
tm. S khng phn tch cng c th xy ra trong nguyn phn gy ra cc
th khm v cc t bo bnh thng v lch bi.
Cc th ba c bit n nhiu loi. thc vt, v d in hnh l
mt lot cc th ba vi nhng c tnh k l loi c c dc Datura
stramonium c Alfred Blakeslee nghin cu vo khong nm 1920.
Thc ra, ngi ta pht hin c tt c cc th ba v tng nhim sc th
trong s 12 nhim sc th khc nhau loi ny; v mi th ba c mt kiu
hnh c trng, th hin r nht l v qu. iu chng t cc nhim
sc th khc nhau c cc hiu qu di truyn khc nhau ln tnh trng ny
(hnh 3.28a). Cc th ba cng c nghin cu nhiu loi cy trng nh
ng, la go v la m nhm xc nh cc nhim sc th mang cc gene
khc nhau. hnh 3.28b cn cho thy hiu qu di truyn ca cc th
khuyt nhim lin quan 7 nhim sc th khc nhau i vi kiu bng ba
ging la m khc nhau (A, B v D).
(a)
(b)
Hnh 3.28 (a) Qu bnh thng ca c c dc Datura (trn cng) v 12

kiu th ba khc nhau, mi kiu c mt v ngoi v tn gi khc nhau.
(b) Cc th khuyt nhim lin quan 7 nhim sc th khc nhau
ba b gen la m (A, B v D) cho cc hiu qu di truyn khc nhau i vi
kiu hnh bng so vi dng bnh thng (hnh cui).
ngi, vic phn tch cc thnh phn nhim sc th ca cc trng

hp sy thai t pht cho thy hu nh tt c cc th mt v nhiu th ba
u l cc dng gy cht thai. Tuy nhin, mt s trng hp vn c sinh
ra vi cc hi chng khc nhau. Ph bin nht l hi chng Down, th ba
nhim sc th 21, vi tn s 1/700 s tr s sinh v thng t l vi tui
98
tc ngi m, c bit l t tui 35 tr i (Hnh 3.29). Hi chng Down

c m t cch y chng 160 nm, ni chung c cc c trng l tr n
v v ngoi chung d thy nh: u to, trn vt, khe mt xch, li hay th
ra ..., thng t vong tui 10-40 v him khi sinh sn.
C s nhim sc th ca hi chng Down c khm ph u tin vo
nm 1959. Kiu nhn ca nhng ngi ny c cho thy cc hnh
3.29c v 3.30a. Danh php hin hnh ch c th c th ba 21 l (47,
+21), trong con s 47 ch ton b s nhim sc th v +21 ch ra rng
c ba bn sao ca nhim sc th 21. Trong s nhng ngi mc hi chng
Down, ch c chng 5% l kiu nhn d hp v chuyn on thun nghch
nh ni trc y, v hu ht (khong 95% trng hp) l kt qu ca
s khng phn tch trong gim phn. Mt kt qu nghin cu gn y cho
thy c im karyotype ca cc trng hp Down nc ta, nh sau:
91% th trisomy 21 thun, 6% th chuyn on nh ni trn v 3% l
th khm (Nguyn Vn Rc 2004).
(a)
(b)
(c)
Hnh 3.29 Hi chng Down
(a) Mt chu b mc hi chng Down (tri) vi c im cu to bn tay. (b)
Mt th v nguy c mc hi chng Down tnh trn 1.000 tr s sinh (trc tung)
lin quan vi cc tui ngi m (trc honh). (c) S hnh thnh cc trng
tha v thiu NST 21 (tri) v s th tinh gia trng tha NST 21 vi tinh trng
bnh thng to ra th ba 21.
99
Cc th ba nhim sc th thng khc l rt him, ch yu l bi v

chng khng sng c khi cn l thai nhi. V d, hi chng Patau, th ba
13 (47, +13), c tn s sy thai l 1/33, tn s bt gp l 1/15.000 tr s
sinh, v sng cha y su thng. Trng hp khc l hi chng Edward,
th ba 18 (47, + 18), tn s bt gp tr s sinh l 1/5.000 v sng khng
n mt nm.
(a)
(b)
(c)
Hnh 3.30 Kiu nhn ca mt s th t bin lch bi thng gp.
(a) Kiu nhn ngi n mc hi chng Down (47, XX, +21);(b) Kiu nhn ngi
mc hi chng Klinefelter (47, XXY). (c) Mt trnh by n gin kiu nhn ca
nhng ngi mc hi chng Turner v Kleinfelter.
Ngoi ra, s khng phn tch ca cc nhim sc th gii tnh ngi

gy ra mt s kiu nhim sc th bt thng ph bin nh: XO, XXX,
XXY v XYY. Chng hn, hi chng Klinefelter XXY (hay 47, XXY) bt
gp tr s sinh vi tn s khong 1/2.000; y l trng hp ca nhng
ngi nam c cc c im nh v sinh, thn hnh cao khng cn i...
100
Kiu nhn ca c th mc hi chng Klinefelter c m t hnh 3.30b.

Nhng ngi mc hi chng XYY (c th gi l "siu nam"), xut hin
vi tn s khong 1/1.000 trong s cc tr nam s sinh; nhng c th ny
khng c v g l bnh tt, sc sng v sinh sn bnh thng. Cc nghin
cu xa hn cho thy dng nh nhng ngi ny c khuynh hng phm
ti, c th c tng quan ti thiu vi hnh vi. Tn s cc c th XYY b
ngi t cao ng k so vi cng ng dn c ni chung; tuy nhin, cha
ti 5% tng s cc c th XYY l c gio dc dy d ng hong. Hi
chng Turner XO (hay 45, X) xut hin tr s sinh vi tn s chng
1/5.000 v tn s sy thai khong 1/18; y l trng hp ca nhng
ngi n v sinh, ln khng cn i, c ngn...Cn hi chng "siu n"
XXX (hay 47, XXX) bt gp tr s sinh vi tn s khong 1/700; hu
nh tt c nhng ngi n mc hi chng ny u v sinh.
Cu hi v Bi tp
1. Th no l chu k t bo? Bng cch no s lng nhim sc th
c trng ca mi loi c duy tr n nh trong qu trnh nguyn phn?
2. Bng cch no s lng nhim sc th t trng thi lng bi gim
xung cn n bi trong qu trnh gim phn? Ti sao ni cc s kin
k trc v k sau ca gim phn I gp phn quan trng trong vic to ra
ngun bin d t hp phong ph a dng cc loi sinh sn hu tnh?
3. So snh nguyn phn v gim phn, v cho bit ngha ca chng.
4. Ti sao trong mi t bo s lng nhim sc th (mc n) v hm
lng ADN (mc c) l khng ng b trong mi giai on ca phn bo?
5. Hai im sai khc chnh gia s sinh tinh v sinh trng ngi v
hu ht cc ng vt c v khc l g? Cc qu trnh pht sinh giao t
ng vt v thc vt bc cao c nhng im ging v khc nhau no?
6. Mt sinh vt c s lng nhim sc th lng bi bng 12, c k
hiu: Aa, Bb, Cc, Dd, Ee v Ff. (a) C bao nhiu t hp nhim sc th
khc nhau c th xut hin trong cc giao t? (b) Xc sut mt giao t
nhn c tt c cc nhim sc th vit hoa l g?
7. (a) C th c nhng kiu bin i no xy ra trong cu trc nhim
sc th? M t nhng nt chnh xy ra trong mi kiu cng vi hu qu v
ng dng ca chng. (b) Gi tn cc trng hp lch bi ph bin ngi
v m t cc thnh phn nhim sc th ca chng.
8. Mt rui gim ci thn en mun ee (e = ebony) ng hp c cho
101
lai vi mt con c hoang di ng hp (e+e+) c chiu tia X. i

con c xut hin mt rui ci thn mun. Khi cho rui gim ny lai vi rui
gim F1 thu c thn mun: hoang di. Hy gii thch kt qu ny.
9. Gi s rng F1 ca php lai bi tp 8 ta pht hin c hai con
rui gim c v ci u c thn en mun. C th ni g v s lng
tng i ca i con nu cho hai con rui gim F1 lai vi nhau? (Cho
bit cc mt on thng gy cht trng thi ng hp).
10. Cho mt cy d hp ABCDE/abcde lai vi mt cy abcde/abcde,
v i con xut hin su dng sau: ABCDE; abcde; Abcde; aBCDE;
ABCDe; abcdE. C iu g bt thng trong kt qu ny v bn c th
gii thch iu ra sao? (Gi : s thiu vng ca hai hoc nhiu kiu
hnh c k vng gi ra mt th d hp o on c lin quan n cc
gene lin kt).
Ti liu Tham kho

Ting Vit
Dubinin NP. 1981. Di truyn hc i cng (bn dch ca Trn nh
Min v Phan C Nhn). NXB Nng Nghip, H Ni.
Kimura M. 1983. Thuyt tin ha phn t trung tnh. (Bn dch ca
Hong Trng Phn). NXB Thun Ha - Hu, 1993 (tr.17-33).
L nh Lng, Phan C Nhn. 1997. C s di truyn hc. NXB Gio
Dc, H Ni.
truyn hc. NXB Gio Dc, H Ni.
Nguyn Vn Rc. 2004. Nghin cu c im karyotype, kiu hnh ca
tr Down v karyotype ca b m. Lun n Tin s Y hc, Trng i
hc Y H Ni, H Ni.
Phm Quang Vinh. 2003. Nghin cu bt thng nhim sc th trong cc
th bnh Leucmie cp ngi ln ti Vin Huyt hc Truyn mu. Lun
n Tin s Y hc, Trng i hc Y H Ni, H Ni.
Ting Anh
Clarke L. 1998. Centromeres: proteins, protein complexes, and repeated
domains at centromere of simple eukaryotes. In: Current Opinion in
Genetics & Developmment, Vol 8, No2 (Allis CD and Gasser SM, eds.),
pp 212-218.
102
Clegg CJ, Mackean DG. 2000. Advanced Biology: Principles and

Applications. 2nd ed, John Murray Published Ltd, London.
Dobie KW, Hari KL, Maggert KA, Karpen GH. 1999. Centromere
proteins and chromosome inheritance: a complex affair. In: Current
Opinion in Genetics & Developmment, Vol 9, No2 (Kadonaga JT and
Grunstein M, eds.), pp 206-217.
Li W-H. 1983. Evolution of duplication genes and pseudogenes. In:
Evolution of Genes and Proteins (Nei M, Koehn RK, eds.), pp. 14-37.
Sinauer Associates Inc.-Publishers, Sunderland, Massachusetts, USA.
Biggins S. and Murray AW. 1999. Sister chromatid cohesion in mitosis.
In: Current Opinion in Genetics & Developmment, Vol 9, No2 (Kadonaga
JT and Grunstein M, eds.), pp 230-236.
Russell PJ. 2003. Essential Genetics. Benjamin/Cummings Publishing
Company, Inc, Menlo Park, CA.
Schrock E, du Manoir S, Veldman T, Schoell B, Weinberg J, FergusonSmith MA, Ning Y, Ledbetter DH, Bar-Am I, Soenksen D, Garini Y, Ried
T. 1996. Multicolor spectral karyotyping of human chromosomes. Science
273: 495.
Verma RS and Babu A. 1995. Human chromosomes: Principles and
Techniques. 2nd ed., McGraw-Hill, Inc, NY. (Ch2-6, pp.6-231).
Mt s trang web
http://www.mhle.com/lewisgenetics5
http://www.genetic.org
http://www.fivepminus.org
http://www.ndss.org
http://www.members.aol.com/cdousa/cdo.htm
http://www.turner-syndrom-us.org
http://www.trisomy.org
103
Chng 4
Di truyn hc Nhim sc th
Nh tho lun cc chng trc, nguyn l phn ly c lp ca
Mendel ch nghim ng trong trng hp cc gene nm trn cc nhim
sc th khc nhau v c l gii bng s phn ly ngu nhin ca cc
nhim sc th trong gim phn. Tuy nhin, vo u thp nin 1910,
Thomas Hunt Morgan (hnh 4.1a) da vo cc kt qu nghin cu rui
gim Drosophila melanogaster (hnh 4.1b) nhn ra rng c nhiu gene
cng nm trn mt nhim sc th. iu khng nh ng n ny sm
b sung v lm sng t cho cc nguyn l di truyn Mendel, ng thi t
nn tng vng chc cho s pht trin ca di truyn hc trong sut na u
th k XX. Trong chng ny, chng ta ln lt tm hiu thuyt di truyn
nhim sc th vi cc vn xc nh gii tnh, cc kiu di truyn lin kt
i vi hai hoc nhiu gene trn cng mt nhim sc th, cng nh cc
phng php kinh in dng lp bn di truyn cc sinh vt.
I. Trng phi Morgan vi thuyt di truyn nhim sc th

T 1910, Morgan cng vi ba cng s l Alfred H.Sturtevant, Calvin
Bridges v Herman J. Muller (hnh 4.1c) xy dng thnh cng thuyt di
truyn nhim sc th (chromosome theory of inheritance) da trn i
tng nghin cu ni ting l rui gim D. melanogaster. Trc tin,
chng ta hy tm hiu c im ca i tng, phung php nghin cu
v ni dung ca hc thuyt ny.
(a)
(b)
(c)
Hnh 4.1 (a) T.H.Morgan; (b) Rui gim D. melanogaster, i tng nghin
cu ni ting ca Morgan; v (c) Herman Muller, mt trong ba mn xut
sc ca Morgan vi phng php gy t bin bng tia X.
1. Tm quan trng ca rui gim Drosophila

1.1. Cc c im v gi tr ca rui gim trong nghin cu di truyn hc
Drosophila melanogaster (hnh 4.1 v 4.2) c l l sinh vt ni ting
104
nht c dng lm sinh vt m hnh (model organism) cho cc nh di

truyn hc. Rui gim thuc lp cn trng (Insecta), b hai cnh
(Diptera). Chng rt thch mi ln men ca cc h da vi c v c bit
l nhng tri cy chn mui nh chui, mt hay cam, chanh..., v vy
chng c bit di ci tn thng dng l rui gim hay "rui tri cy"
(fruit-flies). Rui gim phn b rng khp cc vng n i v nhit i
trn hnh tinh chng ta.
(a)
(b)
Hnh 4.2 (a) S khc nhau v hnh thi ngoi gia rui gim c (trn) v
rui gim ci (di); v (b) b nhim sc th lng bi 2n = 8 ca chng, vi
cp nhim sc th gii tnh XY- con c (tri) v XX- con ci.
Gi tr ca rui gim Drosophila trong cc th nghim di truyn nm

trong cc c im sau (cc hnh 4.2, 4.3 v 4.4):
- Mi cp rui gim sinh c hng trm con trong mt la;
- Vng i ngn, ch c hai tun l l chng c th nhanh chng t ti
tui trng thnh tham gia sinh sn; v chu k sng c th rt xung
cn 10 ngy, nu nhit 25oC. Cc rui ci trng thnh v mt sinh
dc ni trong 12 gi, v chng li trng ha nhng trong hai ngy..
- Sau khi giao phi, cc con ci c th bo qun cc tinh trng, v vy
cn thit phi tin hnh cc php lai vi cc con ci ang cn trinh
(virgin). Rui ci cn trinh c th d dng nhn ra qua mu ct su
(meconium) hay xm nht ca c th chng (hnh 4.3d) v phn nhng
di dng chm en c th nhn thy xuyn qua vng bng.
- Rui gim Drosophila tng i d nui, v d dng phn bit cci cc giai on non v trng thnh cch ly v tin hnh lai. Bn
cnh s phn bit ngoi hnh cc rui non cn trinh nh ni trn, giai
an trng thnh rui c thng khc vi rui ci cc im sau: c
th b hn; vng bng di c ba vch en vi vch di cng rng, trong
khi rui ci c nm vch ri nhau; chm bng con c hi trn v con
ci nhn (hnh 4.2a).
- B nhim sc th y ca cc t bo soma rui gim ch c bn
cp, 2n = 8 (hnh 4.2b). Ton b b gene ca Drosophila c xc nh
trnh t trong thi gian gn y.
105
(a)
(e)
(i)
(b)
(f)
(j)
(c)
(g)
(d)
(h)
(k)
(l)
Hnh 4.3 Mt s th t bin quan trng ca rui gim Drosophila.

Ch thch: (a-b) th t bin mt trng v mt kiu di; (c) con c trng
thnh (tri) v con c cn trinh c mu ct su; (d) con ci trinh c mu ct su;
(e) cc dng t bin khc nhau v cnh; (f) th t bin ny l mt v d v hai
kiu hnh cnh ngn/thn mu en mun; (g) th t bin cnh qun con ci
(tri) so vi con ci bnh thng; (h) th t bin hai t ngc; (i) th t bin
antennapedia- kiu chn ru v (j) anten kiu di; (k) so snh th t bin anten
(di) v dng bnh thng (trn); (l) Mt kiu di vi cc dng mt thi (Bar
eye) d hp v ng hp (theo th t t trn xung).
- Rui gim c nhiu tnh trng, c bit l cc th t bin t pht

nh mt trng hoc c to ra trong phng th nghim (nh thn en,
cnh ngn, cnh qun, mt nu...); cc tnh trng ny c th phn bit bng
mt thng, knh lp hoc knh hin vi quang hc (hnh 4.3 v 4.5).
- Cc t bo tuyn nc bt ca u trng rui gim (hnh 4.4) c cha
cc nhim sc th khng l a si (nh gii thiu chng 3); y l
im thun li cho vic xc nh cc phn c th ca cc nhim sc th.
Cc bng ny t chng khng phi l cc gene nhng rt hu ch cho vic
lp bn cc gene trn cc nhim sc th.
106
Hnh 4.4 Cc a mm (trong u trng)

t hnh thnh nn cc c quan ca
rui gim trng thnh. T trn xung:
cc phn ph ming, mnh trn v mi
trn, anten, mt, chn, cnh v c quan
sinh dc.
Ngoi ra, cc dng c v ha cht

c s dng trong cc th nghim
rui gim l tng i n gin, c
gii thiu hnh 4.5 di y.
(a)
(b)
(c)
Hnh 4.5 Cc dng c th nghim vi rui gim. (a) ng nghim nui v lai
rui gim; (b) khay ng cc l ha cht v mt s vt dng khc; v (c) knh
hin vi quang hc dng cho nghin cu hnh thi v t bo hc.
1.2. Cc tnh trng c kim sot v mt di truyn ca rui gim

Mt qun th bnh thng ca rui gim Drosophila bao gm cc con
rui in hnh c thn xm, ccnh di v mt . Dng rui gim ny l
ph bin nht, v c cc nh di truyn hc xp vo kiu di (wild type).
Nhiu dng t bin cng c pht hin trong t nhin. Mt con rui
t bin c mt xut pht im di truyn t nht l mt trong s cc tnh
trng ca dng rui gim bnh thng. Cc tnh trng t bin c bit
n bng mt tn gi. V d:
t bin
tn gi
k hiu
c tnh
mt trng
trng (white)
w
ln
thn en mun
mun (ebony)
e
ln
cnh ngn
ngn (vestigial)
vg
ln
mt nu
nu (brown)
bw
ln
mt thi (Bar)
Bar
B
tri
Cc th t bin ln c k hiu bng cc ch ci vit thng, v cc
tnh trng tri tng ng c biu th bng cc ch ci vit hoa.
107
Trong cc th nghim lai di truyn, allele bnh thng mt locus c

th c cc nh di truyn hc trc y k hiu bng du "+". K hiu
ny thng c b qua mc nhp mn, mc d n thng c dng
cho rui gim. Tuy nhin, i vi bc i hc, cc alelle bnh thng
c quy cho "kiu di" v s dng cc k hiu ca cc nh di truyn hc.
2. Thuyt di truyn nhim sc th
Rui gim Drosophila melanogaster c nh di truyn hc ngi
M (USA), T.H. Morgan (1866-1945), s dng trong nghin cu di truyn
hc t nhng nm u ca th k XX, trong khi ang lm vic ti Hc
vin Cng ngh California (California Institute of Technology). Nh s
dng rui gim ny, Morgan v cc cng s ca mnh xy dng thnh
cng hc thuyt di truyn nhim sc th (chromosome theory of heredity).
Trc tin, ta hy tm lc cc ni dung chnh ca thuyt di truyn
nhim sc th v nhng ng gp ca trng phi Morgan cho s pht
trin ca di truyn hc.
(1) Hc thuyt ny xc nhn rng: gene l n v c s ca tnh di
truyn nm trn nhim sc th. Trn mi nhim sc th c nhiu gene
phn b thng hng, mi gene chim mt v tr xc nh gi l locus; cc
gene trn mi nhim sc th hp thnh mt nhm lin kt. S nhm lin
kt gene chnh l s nhim sc th n bi, cn gi l b gene (genome).
(2) Trong qu trnh gim phn, cc gene trn cng nhim sc th c xu
hng phn ly cng nhau v giao t. y l c s ca hin tng di truyn
lin kt gene hon ton v di truyn lin kt (linkage) ni chung.
(3) Tuy nhin, trong qu trnh gim phn c th xy ra s trao i
cho (crossing over) mt s on gia hai nhim sc th tng ng,
ko theo s trao i cc gen gia chng, cn gi l ti t hp hay hon v
gene. y chnh l c s ca hin tng lin kt gene khng hon ton.
(4) Tn s ti t hp (rate of recombination) ca cc gene l mt s
hu t, tha mn gii hn t 0,0 n 0,5 (tc khng vt qu 50%). i
lng ny t l thun vi khong cch gia cc gene v ph thuc vo mt
s yu t khc nh gii tnh cng nh mc c ch bi cc trao i cho
ng thi ti nhiu im trn mt cp tng ng. Da vo cc tn s ti
t hp gene ny ta c th thit lp bn nhim sc th (chromosome
map) ca cc loi, hay cn gi l bn lin kt (linkage map).
(5) Vn cc nhim sc th xc nh gii tnh (sex-determining
chromosomes) v hin tng di truyn lin kt vi gii tnh (sex linkage)
c lm sng t ln u tin bi hc thuyt ny.
(6) Ngoi ra, trng phi ca Morgan xc nh rng: gene - n v
108
di truyn hc then cht ny ng ba vai tr: (i) Gene l n v chc nng,

ngha l gene c xem nh mt th thng nht ton vn kim sot mt
tnh trng c th. (ii) Gene l n v ti t hp, ngha l gene khng b chia
nh bi s trao i cho (v theo quan im ny, trao i cho khng xy
ra bn trong phm vi mt gene m ch xy ra gia cc gene); nh th gene
c coi l n v cu trc c s ca vt cht di truyn, nhim sc th.
(iii) Gene l n v t bin, ngha l nu t bin xy ra trong gene d
bt k v tr no hoc vi phm vi ra sao, ch gy ra mt trng thi cu trc
mi tng ng vi mt kiu hnh mi, kiu hnh t bin, khc vi kiu
hnh bnh thng. Tuy nhin, quan nim ny vn cn cha r rng v
khng thc s chnh xc theo quan im ca di truyn hc hin i (s
c tho lun chng 6).
Trong vic xy dng hc thuyt di truyn nhim sc th, phi k n
nhng ng gp to ln ca cc mn xut sc ca Morgan, l: Alfred
H.Sturtevant vi vic xut phng php xy dng bn di truyn nm
1913; Calvin Bridges vi vic pht hin ra c ch xc nh cc kiu hnh
gii tnh rui gim nm 1916; v Herman J.Muller vi s pht trin
phng php gy t bin bng tia X nm 1927. Nh ng gp to ln ,
Morgan c trao gii thng Nobel nm 1933 v Muller - nm 1946.
II. S xc nh gii tnh (sex determination)

C ch t nhin m trong mt c th ca mt loi phn tnh
(dioecious species) tr thnh con c hoc con ci (hay lng tnh,
hermaphroditic) c gi l xc nh gii tnh (sex determination). Thc
ra, khng c mt phng thc ph bin no cho vic xc nh gii tnh;
nhng cho n nay, cc nh sinh hc khm ph ra nhiu c ch xc
nh gii tnh, tp trung vo hai tiu ch sau (xem cc Bng 4.1- 4.3).
mt s loi, gii tnh c xc nh sau khi th tinh bi cc nhn t mi
trng nh nhit hoc s c mt ca cc th km gii tnh. Kiu xc
nh gii tnh ny c gi l xc nh gii tnh do mi trng
(environmental sex determination = ESD). cc loi khc, gii tnh c
xc nh lc th tinh bng s t hp ca cc gene m hp t nhn c.
Kiu xc nh gii tnh ny c gi l xc nh gii tnh do kiu gene
(genotypic sex determination = GSD). Di y chng ta ln lt xt qua
hai h thng ny (v chi tit, xem trong: Kalthoff 1997, tr.660-685; v
Yablokov 1986, tr.17-30). Ring vn bt hot nhim sc th X s c
tho lun mc II-3-2, v n c lin quan n di truyn lin kt gii tnh.
1. S xc nh gii tnh do kiu gen (GSD)
hu ht cc sinh vt, gii tnh c xc dnh bng s sai khc nhim
sc th v cc gene trn chng (bng 4.1). V d u tin v s xc nh
109
gii tnh do nhim sc th c ghi nhn rp Protenor nm 1905, trong

cc con ci c khm ph c hai nhim sc th X v con c ch c
mt X. Cc giao t c c th c mt X hoc khng c nhim sc th X
c bit l c t l ngang nhau, v cc giao t ci th lc no cng mang
mt X, v vy s lng i con c XX (ci) v X (c) l ngang nhau.
Sau khng lu, nhiu nh nghin cu xc nh s c mt ca
mt nhim sc th gii tnh Y cc sinh vt khc. cc loi ny, s c
mt ca Y cng vi mt X cho ra con c, trong khi hai bn sao ca X
sinh ra mt con ci. Vi li, cc giao t c gm hai kiu, v vy c s
lng tinh trng hay ht phn mang X v mang Y bng nhau. Trong
trng hp gii tnh c c hai kiu nhim sc th gii tnh nh th, th
kiu XY c gi l gii tnh d giao t (heterogametic sex), cn kiu XX
c gi l gii tnh ng giao t (homogametic sex). hnh 4.6 cho thy
cc nhim sc th X v Y, v c ch xc nh gii tnh ngi.
mt s sinh vt thuc cc lp nh chim v b st th ngc li, cc
con c (trng) l ng giao t v cc con ci (mi) l d giao t. trnh
s nhm ln, ngi ta thng gi cc nhim sc th gii tnh ny l Z v
W; nh vy cp nhim sc th gii tnh con c l ZZ v con ci l ZW.
Kt qu l, cc con ci cho hai loi giao t (mt loi mang Z v mt loi
mang W vi t l ngang nhau), trong khi cc con c ch cho mt loi
giao t tt c u mang mt nhm sc th Z. S hiu bit v gii tnh ny
cng vi s di truyn lin kt gii tnh c ngha thc tin to ln trong
chn nui gia cm. Vn ny s c tho lun tr li cui mc III.
Bng 4.1 Cc kiu xc nh gii tnh khc nhau bi nhim sc th
Sinh vt
Hu ht ng vt c v, mt s cn trng (tt c
bn hai cnh), mt s c, mt s thc vt
Rp Protenor, mt s cn trng khc, kangoroo
Lp chim, hu ht cc b st, bm m
B cnh mng (Hymenoptera)
Con ci
Con c
XX
XX
ZW
Lng bi
XY
X
ZZ
n bi
Hu nh tt c cc ng vt c v, s c mt ca mt nhim sc th
Y cn thit cho s pht trin ca kiu hnh ging c. Chng hn, nhng
ngi mc hi chng Turner (45, X) u l n. Hn na, nhng ngi
mc hi chng Klinefelter (47, XXY hoc 48, XXXY) u l nam mc d
h c th c ti hai hoc ba nhim sc th X. iu chng t nhim sc
th Y c cha gene xc nh tnh c (maleness). Ngy nay ta bit r rng
chnh l nhn t xc nh tinh hon (TDF = testis-determining factor)
nm trn vai ngn nhim sc th Y (hnh 4.6c). Sinclair v cs (1990) gi
110
n l gene SRY (sex-determining region Y).

vng gi NST thng
vai p
vai q
(a)
(b)
vng gi nhim
(c) sc th thng
Hnh 4.6 (a) Cc nhim sc th X v Y ng vt c v, i din l ngi.

(b) C ch xc nh gii tnh ngi. (c) Nhim sc th Y ca ngi vi
gene SRY nm k vng gi nhim sc th thng u mt ca vai ngn.
Cn lu rng, gn y ngi ta cng xc nh c gene "chuyn

i" (switch gene) SRY trn nhim sc th Y bng cch kim tra mt vi
c th him hoi b o ngc gii tnh (sex-reversed), ngha l con c
XX v con ci XY. Cc con c XX thc t c mang mt mu ca Y cha
gene xc nh tnh c, cn cc con ci XY th li thiu hn vng nh vy
Y. Chng hn, mt vi bnh nhn o ngc gii tnh vn l nhng
ngi nam v sinh r rng l mang c hai nhim sc th X v khng c Y,
v mt s ngi n mc hi chng Turner th li mang mt X v mt Y r
rng. Cc kt qu phn tch k hn (trn bn ngi bnh o ngc gii
tnh nh p dng cc vt d DNA c to dng t nhim sc th Y vo
Southern blots ton b DNA b gene ca h) cho thy rng hu ht cc
trng hp ny u c lin quan n s chuyn mt on DNA c th
trn nhim sc th Y (nm st vng gi nhim sc th thng pseudoautosomal region); v chnh s chuyn on ny gy ra hin
tng o ngc gii tnh. iu ny c gii thch l do cc s kin trao
i cho him hoi gia X v Y trong gim phn ngi nam hay con c.
Lu rng gene SRY+ m ha mt protein bm DNA v n c bo tn
cao cc ng vt c v. John Gubbay v cs (1990) pht hin ra mt
gene tng ng chut, k hiu l Sry+, khng c mt trong chut ci
XY b o ngc gii tnh. rui gim, c mt th t bin autosome ca
gene "chuyn i", tra (transformation), m khi trng thi ng hp
trong cc c th XX bin i chng thnh nhng con c, ch khng phi
l cc con ci nh k vng. Tnh hung ngc li c bit ngi, trong
cc c th mang mt t bin trn nhim sc th X c mt trng thi
gi l n ha tinh hon (testicular feminization). Trong trng hp ny,
cc c th XY v mt kiu hnh l n, c ngc n nang v m o, nhng
111
h u v sinh. t bin ny hin nhin l c lin quan ti mt cht mang

hormone m n ngn khng cho nhng ngi ny tit ra testosterone; v
hu qu l h khng pht trin c cc tnh trng nam th cp.
Bng 4.2 T l X/A v cc kiu hnh gii tnh ca rui gim D. melanogaster
(theo Bridges 1921, trch t Yablokov 1986)
B nhim
sc th (*)
3X : 2A
4X : 3A
4X : 4A
3X : 3A
2X : 2A
1X : 1A
3X : 4A
2X : 3A
1X : 2A
2X : 4A
1X : 3A
T l
X/A
1,50
1,33
1,00
1,00
1,00
1,00
0,75
0,67
0,50
0,50
0,33
Kiu hnh gii tnh

Siu ci
Siu ci
Ci t bi
Ci tam bi
Ci lng bi
Ci n bi
Gii tnh trung gian
Gii tnh trung gian
c lng bi
c t bi
Siu c
Ghi ch
Bt th, tnh trng thin v ci
Bt th, tnh trng thin v ci
Hu th
hu th gim
Hu th
Bt th
Bt th
Bt th
Hu th
Hu th
Bt th, tnh trng thin v c
(*) X - s nhim sc th X, A - s b n bi nhim sc th thng.
Mc d rui gim Drosophila nhng con ci l XX v con c l

XY, song s c mt ca Y khng nht thit cho kiu hnh c (nh ng
vt c v). Chng hn, cc kiu hnh ngoi l ny c Calvin Bridges,
mt hc tr xut sc ca Morgan, pht hin t nm 1916 l cc con c
XO c mt v cc con ci XXY mt trng. Sau , Bridges pht trin
cc ni rui gim tam bi. Khi kim tra cc c th c s lng nhim sc
th X khc nhau, ng pht hin ra rng kiu hnh gii tnh rui gim l
mt hm s ca t l gia s lng cc nhim sc th X (X) v s lng
cc b nhim sc th thng (A). V d, bng 4.2 cho thy cc con ci
bnh thng c hai nhim sc th X v hai b nhim sac th thng,
ngha l t l X/A = 2/2 = 1. Cc con c bnh thng c mt X v hai b
nhim sc th thng, do X/A = 1/2 = 0,5. Cng vy, cc con c v
ci ngoi l vn c cc t l tng ng l 0,5 v 1,0. Khi Bridges kim tra
cc con rui c ba nhim sc th X v hai b nhim sc th thng, tc
3/2 = 1,5, ng thy rng chng u l cc con ci bt dc (i khi gi l
"siu ci", metafemales), trong khi cc con rui c mt X v ba b nhim
sc th thng, X/A = 1/3 = 0,33, u l cc con c bt dc hay gi l
dng siu c (metamales), Cui cng, cc con rui c hai X (XX) v ba
b nhim sc th thng, X/A = 2/3 = 0,67 v chng c cc c im kiu
hnh ca c hai gii v c gi l gii tnh trung gian (intersexes). T
cc pht hin ny, Bridges ngh rng, nhn chung, cc nhim sc th X
112
xc nh gii ci v cc nhim sc th thng (autosomes) xc nh gii

c. Ni cch khc, khi t l X/A l 1 hoc ln hn, cc rui gim s c
ku hnh ci, v khi t l X/A l 0,5 hoc nh hn th chng s c kiu
hnh c. Tuy nhin, ta cn lu rng mc d thm ch nhim sc th Y
khng nht thit cho kiu hnh c rui gim, nhng n nht thit cn
cho hu th (cc con c XO v cc con rui siu c u bt dc).
Ngoi ra, cc sinh vt thuc b cnh mng (Hymenoptera) nh ong
mt v ong bp cy, chng khng c nhim sc th gii tnh; trong trng
hp ny, nh ni chng 3, con ci l lng bi v con c l n
bi. V d, ong mt (Apis mellifera), cc ong ci bao gm c ong cha
ln ong th l lng bi (2n = 32) v cc ong c - n bi (n = 16). Khi
gim phn, ong cha cho cc giao t ci (n = 16), v ong c vi hin
tng lng bi gi gim phn cho cc giao t c (n = 16). Cc trng
c th tinh (2n = 32) pht trin thnh cc ong ci, ch mt vi con c
u tin mm sa cha lin tc trong 3-5 ngy u s pht trin thnh ong
cha; cn cc trng khng c th tinh s pht trin thnh cc ong c.
2. S xc nh gii tnh do mi trng (ESD)
Mt trng hp ni bt nht v xc nh gii tnh do mi trng l
Bonellia viridis, mt loi u trng giun bin (Leutert 1975). Cc con ci
trng thnh ca loi ny bm vo cc mm i dng. C th con
ci di hn 10 cm, con c rt b (1-3 mm) sng k sinh bn trong con
ci. Cc u trng ca Bonellia sng nh l thnh phn ca sinh vt tri ni
(plankton), ngha l, cc sinh vt nh b di chuyn th ng trong nc.
S xc nh gii tnh xy ra khi cc u trng c th tinh trn mt gi th
v bin thi. Nhng u trng c th tinh trong s cch ly (sng t do)
th pht trin thnh cc con ci, trong khi cc u trng chui vo trong
mt con ci trng thnh th tr thnh cc con c. Mt s trng hp
khc, chng hn nh cc trng c su chu M (Alligator) c a vo
nhit cao cho ra hu ht l con c, cn nu nhit thp cho ra hu
ht l con ci. ra th ngc li (xem bng 4.3).
Bng 4.3 Cc kiu xc nh gii tnh khc nhau do mi trng (ESD)
Loi
C ch
Ra (Turtles)
C su (Alligators)
Meloidogyne incognita
Bonellia viridis
Nhit
Nhit
Mt qun th
S c mt con ci
Cc gii tnh
m: ci
Lnh: ci
Phn tn: ci
C: c
Lnh: c
m: c
Tp trung: c
Khng: ci
Ngun: Hodgkin (1992), trch chn theo sa i ca Kalthoff (1997, tr.662).
113
Ngoi ra, gii tnh ca mt s loi c chu nh hng bi u th sng

thnh n, cn cc loi thc vt no li cho cc gii tnh khc nhau ty
thuc vo di ngy hoc cc nhn t khc nh hng ln tc sinh
trng ca chng.
Tm li, cc loi sinh sn hu tnh giao phi, ni chung t l c/ci
trn quy m qun th-loi l xp x 1:1, v c th gii thch bng c ch
phn ly ca cc nhim sc th gii tnh v cc giao t trong qu trnh gim
phn v s kt hp ngu nhin ca chng trong th tinh.
III. S di truyn lin kt vi gii tnh (sex-linked inheritance)

Trong cc chng 1 v 2 chng ta mi ch cp n cc gene trn
nhim sc th thng (autosomes), tc cc nhim sc th tn ti trong cc
t bo soma ng ngha l cc cp tng ng; v vy m cc kt qu lai
thun nghch l tng ng nhau. Tuy nhin, mt s th nghim ca
Morgan rui gim vo nm 1910 cho thy cc kt qu lai thun nghch
(reciprocal crosses) l khc nhau. Di y ta xt mt s trng hp di
truyn lin kt vi gii tnh ch yu rui gim v ngi, mi lin quan
gia di truyn lin kt gii tnh v s bt hot ca nhim sc th X, cng
nh s di truyn ca mt s tnh trng b gii hn bi gii tnh v chu nh
hng ca gii tnh.
1. c im di truyn ca cc gen trn nhim sc th X v Y
Bn cht ca cc nhim sc th gii tnh X v Y l khc nhau (hnh
4.6). Trong khi nhim sc th X thng rt ln v mang nhiu gene kim
sot ch yu cc tnh trng thng, th nhim sc th Y li rt b v cha t
gene. V vy s di truyn lin kt vi gii tnh (sex-linked inheritance), tc
s di truyn ca cc gen trn cc nhim sc th gii tnh cng khc nhau.
1.1. S di truyn lin kt - X
Hin tng di truyn lin kt gii tnh c Morgan khm ph ln u
tin rui gim Drosophila. Bnh thng mu mt ca rui gim c mu
. Trong mt qun th Drosophila nui qua nhiu th h, Morgan pht
hin mt th t bin mt trng rui c (xem hnh 4.3a-b). Khi cho lai
gia rui c mt trng ny vi rui ci mt thun chng, i con F1
nhn c tt c mt (ng nh k vng allele mt trng l ln). Sau
khi cho tp giao cc rui F1 vi nhau, F2 thu c 2.459 rui ci mt ,
1.011 rui c mt v 782 rui c mt trng. Nhn chung, t l :
trng khng gn vi t l 3:1. Tuy nhin, kt qu bt ng l tt c cc con
rui mt trng u l c (hnh 4.7a)! Hn na, khi cho rui c mt trng
lai vi rui ci mt F1, i con sinh ra gm c hai loi mt v trng
mi gii tnh vi t l tng ng. iu chng t tnh trng mt
114
trng phn b c hai gii, ch khng phi ch gii c. Mt khc, khi

tin hnh php lai nghch gia rui ci mt trng F2 trong th nghim ni
trn vi rui c mt , kt qu thu c khc vi php lai thun trc
y, tt c rui ci mt v tt c rui c mt trng (hnh 4.7b).
Tinh trng
Trng
Ci d hp mt
c bn hp t mt trng
(a)
(b)
Hnh 4.7 Cc php lai thun nghch v mt trng v mt rui gim. (a)
Php lai thun: P = ci mt c mt trng F1 tt c F2 3 : 1
trng (mt trng ch c gii c); v (b) Php lai nghch: P = ci mt trng
c mt F1 gm tt c rui ci mt v tt c rui c mt trng.
Vi cc kt qu , Morgan cho rng cc tnh trng mt v mt

trng ny di truyn lin kt gii tnh, do cc allele tri (w+) v (w) ln
tng ng nm trn nhim sc th X kim sot; con ci l XX v con
c l XY. V thut ng bn hp t (hemi-zygote) c ng dng m
t trng hp ny.
Ta c th tm tt cc c im ca s di truyn lin kt X nh sau: (1)
Mt c th ci d hp t s truyn allele ln cho mt na con ci v mt
na con c ca n. (2) Allele ln con c tn ti trng thi bn hp t
s biu hin ra kiu hnh ln (nn kiu hnh ln ny ph bin gii c),
v con c s truyn allele ln ny cho cc con ci (female) ca n. (3)
Hin tng di truyn allele ln t b cho con gi v biu hin chu ngoi
115
trai nh th r rng l c s cch qung th h, v n c gi l di truyn

cho. (4) Ni chung, vic nhn bit mt tnh trng no tun theo quy
lut di truyn lin kt-X c th da vo cc t l kiu hnh khc nhau t
cc php lai thun nghch, hoc s phn b khng u ca cc kiu hnh
hai gii, hoc bng cch s dng "php th c lp" (quy tc nhn) nh
ni chng 1.
By gi ta xt s qua s di truyn lin kt gii tnh (cc gene trn X)
ngi. Nm 1994, McKusick lit k 161 locus c xc nh trn
nhim sc th X ngi. Tuy nhin, theo thng k ca OMIM, tnh n
ngy 8/2/2005 con s ny l 539 (OMIM 2005) trong tng s hn 1.400
gene cha trong 150 triu cp base ca nhim sc th ny (NCBI 2005).
D nhim sc th X mang hng trm gene nh vy nhng rt t gene ny,
nu c, trc tip tc ng ln gii tnh. Tuy nhin, nh ni, s di truyn
ca cc gene ny tun theo cc quy tc c bit, v: (i) ngi nam ch c
mt nhim sc th X n c; (ii) hu nh tt c cc gene trn X khng c
cc gene tng ng trn Y; do vy (iii) bt k gene no trn X s c
biu hin nam gii, d n l ln n gii. Nhng ngi n d hp t
c gi l "th mang" (carrier) v mc d h khng cho thy cc triu
chng, nhng li truyn gene ny cho khong mt na s con trai (s pht
trin bnh) v mt na cho con gi ca h (cng l cc th mang).
Mt v d quen thuc v s di
truyn lin kt-X l bnh mu kh
ng (hemophilia) do mt allele
ln ca gene hemophilia A nm
gn u mt vai di gy ra (hnh
4.8). Cc c th b bnh ny mt
kh nng tng hp mt protein
(nhn t VIII) cn thit cho s
ng mu bnh thng. Mt ph
h ni ting ca bnh ny bt u
t gia nh n hang Victoria
nc Anh (England). Mt trong
s cc con trai ca n hang b
bnh mu kh ng, v hai trong
s cc c con gi ca b l cc th
d hp t v gene ny ( sinh ra
Gene SRY
(TDF)
Hnh 4.8 Bn nhim sc th X ca ngi (bn tri) cho thy v tr

mt s gene bnh, v s khng tng ng gia n vi nhim sc th Y.
116
ba chu ngoi trai ca b u mc bnh mu kh ng v bn chu ngoi

gi tt c u d hp t). Cc allele ln t hai trong s bn c gi (chu
ngoi) d hp t ny c nhp vo cc gia nh hong tc ca Nga v
Ty Ban Nha. Cn gia nh hong tc nc Anh hin gi do pht xut t
mt hong t bnh thng ca n hong nn khng mc bnh ny. Hnh
4.9 cho thy gia nh ca Czar Nicholas II nc Nga (Russia), trong
ngi v Alexandra chnh l chu ngoi gi ca n hong Victoria. Cu
con trai Alexis ca h (pha trc hnh) mc bnh hemophilia v b
hnh hnh tui 14. Trong khi bn c con gi ca h u bnh thng.
i vi bnh hemophilia, cc kiu gene v kiu hnh ca nhng ngi n
v nam thng c biu din nh sau:
N
Kiu gene
H
X X
XHXh
XhXh
Kiu hnh
bnh thng
th mang
bnh
Nam
Kiu gene
H
X Y
XhY
Kiu hnh
bnh thng
bnh
Bnh hemophilia ch nh hng n 0,004% (hay 1/25.000) trong s nam

gii ca qun th, ngha l tn s allele ny bng 0,00004. Vy xc sut
cho mt ngi n mc bnh ny l khong (0,00004)2.
Hnh 4.9 Mt bc nh ca gia
nh Hong Czar Nicholas
II. V ng, Czarina Alexandra,
ngi bn tri, vi bn c con gi
tt c u c mu ng bnh
thng, v ring mi cu con
trai Alexis (pha trc) b bnh
hemophilia.
Mt trng hp khc kh ph bin l bnh m mu -lc (red-green

colour blindness). Nhng ngi mc bnh ny khng th phn bit cc
mu m nhng ngi khc nhn thy nh mu lc, vng, cam v
(chng c nhn thy nh l mt mu). pht hin dng bnh ny
ngi ta s dng cc s mu chng hn nh Phiu trc nghim m mu
ca Ishihara (Ishihara's tests for colour blindness). Bnh ny do mt allele
ln trn X (nm gia hai gene hemophilia A v B) gy ra; nam gii c
khong 8% mc bnh ny trong khi n ch khong 0,4%.
Ngoi ra, ri lon dng c Duchenne (Duchenne muscular distrophy
= DMD) l mt cn bnh qui c thm thng m hu ht xy ra tr em,
cuc i chng gn cht vi chic xe ln, ht th cng kh khn. Hin gi
117
mt ngi bnh ny cng him khi sng st qu 20 tui. Bnh DMD nh

hng ti 1 trn 4.000 tr em nam, v khong 1/3 trong s l hu qu
ca cc t bin t pht trong gene ny. Gene DMD nm trn vai ngn ca
nhim sc th X (xem hnh 4.8). Theo s liu hin gi, gene DMD l gene
c kch thc ln nht, khong 2,4 triu cp base, tng ng khong 1,5%
chiu di ca nhim sc th X (2,4x106 : 150 106 = 0,016).
Trc khi kt thc phn ny, ta hy cp mt vi ng dng thc tin
ca s hiu bit v di truyn gii tnh v lin kt vi gii tnh. Trong chn
nui gia cm, vic xc nh gii tnh lc chng cn non hoc thm ch
giai on trng tht l quan trng. Chng hn, g, mt gene trn nhim
sc th Z c mt allele ln xc nh mu lng vng (ZsZs hoc ZsW), v
mt allele tri xc nh lng bc (ZSZS, ZSZs hoc ZSW). Khi cho lai gia
con mi lng bc (ZSW) v con trng lng vng (ZsZs) s cho i con tt
c con trng lng bc (ZSZs) v tt c con mi lng vng (ZsW). R rng
l, vi hiu bit quy lut di truyn cho, cho php ta d dng xc nh gii
tnh khi g con mi mt ngy tui. Bn hy kim tra php lai ngc li
(chng hn ZSZS ZsW) xem th liu php lai ny c th dng xc
nh gii tnh ca cc g con mi n hay khng?
1.2. S di truyn lin kt-Y
Ni chung, nhim sc th Y rt b, cha t gene. Nhim sc th Y
rui gim hu nh khng mang gene, trong khi ngi c 48 gene
bit trnh t trong tng s hn 200 gene c c tnh l cha trong
khong 50 triu cp base (OMIM-NCBI 2005). hai u mt ca nhim
sc th Y c hai vng c gi l cc vng gi nhim sc th thng
(pseudoautosomal regions; hnh 4.6c) bi v cc gene nh khu bn trong
chng (cho n nay ch pht hin c 9 gene) u c di truyn ging
nh bt k cc gene no thuc nhim sc th thng. V s trao i cho
gia X v Y ch c th xy ra hai vng tng ng rt nh ny ca Y.
Mc d 95% ca nhim sc th Y nm gia cc vng gi tng ng,
nhng s gene c pht hin y l cha ti 80. Mt s gene ny m
ha cc protein dng chung cho tt c cc t bo (v c hai gii tnh).
Nhng gen cn li m ha cc protein hnh nh ch hot ng trong cc
tinh hon. Gene ch cht nht nhm sau l gene xc nh tinh hon
TDF, hay gene SRY, nh khu trn vai ngn ngay bn ngoi vng gi
nhim sc th thng (hnh 4.6c). Cc tnh trng c quy nh bi cc
gene nm vng khng tng ng ny ca Y c di truyn theo ng
thng (straightforward), ngha l: (i) Chng ch biu hin nam gii; v
(ii) chng lun lun c truyn t b cho con trai.
2. S bt hot ca nhim sc th X v mt s vn lin quan
118
tt c cc ng vt c v k c ngi, nhim sc th X khc bit vi

cc nhim sc th khc ch ch c mt chic hot ng trong mt t bo.
Cc con ci (gi) c hai nhim sc th X, bnh thng ch mt chic l
hot ng v chic kia bt hot. Nhim sc th X bt hot kt vn to
thnh mt cu trc bt mu ti sm, thng c dng thu knh li bm vo
mt trong mng nhn, gi l th Barr (Barr body) (hnh 4.10). N mang
tn ca ngi khm ph u tin l Murray Barr. Cc con c bnh thng
ch c mt X v trng thi hot ng trong tt c cc t bo, do vy
khng c th Barr. V nguyn tc, s th Barr bng s nhim sc th X (
hnh 4.10B, k hiu l N) tr i mt.
(A)
(B)
Hnh 4.10 (A) nh chp cc nhn t cc t bo ca (a) mt con ci (XX)
vi mt th Barr, (b) mt con c (XY) vi khng th Barr no, v (c) mt
con ci XXX vi hai th Barr. (B) S minh ha s hnh thnh th Barr
trong cc trng hp khc nhau.
C ch bt hot-X: S bt hot ca mt nhim sc th X cn n

mt gene trn nhim sc th ny gi l XIST. Gene XIST m ha mt phn
t RNA ln (mt kiu khc vi cc RNA, nh mRNA, c s dng trong
tng hp protein). Phn t RNA ca gene XIST tch t dc theo nhim sc
th X c cha gene XIST hot ng v gy bt hot tt c (hoc hu nh
tt c) hng trm gene khc trn nhim sc th . Mt im cn lu l,
RNA ca gene XIST khng di chuyn trn nhim sc th X no khc
trong nhn. Cc th Barr l nhng nhim sc th X bt hot c "sn
pht " (painted) bi RNA XIST. (Rastan 1994; Lee v Jaenisch 1997).
Trong nhng giai on u ca s pht trin phi ci, locus XIST trn
mi trong s hai nhim sc th X ca n c biu hin nhng RNA XIST
nhanh chng b b gy. Ri mt iu g xy ra thng bo trc s
119
cn bng i vi mt chic ny hoc chic kia ca cc nhim sc th X.

S phin m tip tc trn mt trong s cc nhim sc th X, dn ti vic
tch t ca RNA XIST v lm bin di nhim sc th thnh ra mt th
Barr bt hot. S phin m ca XIST dng li trn nhim sc th X khc
cho php tt c hng trm gene khc ca n c biu hin. S tt ngm
ca locus XIST trn nhim sc th X hot ng c tin hnh bng vic
methyl ha cc trnh t iu ha XIST (XIST regulator sequences). S
methyl ha DNA (DNA methylation) thng xy ra trong biu hin gene
cho nn s methyl ha kha cht hn s biu hin ca gene XIST v n
cho php biu hin lin tc ca tt c cc gene lin kt-X cn li. Ngoi ra,
s bt hot-X phi ci l hon ton ngu nhin i vi mt trong hai X
(hnh 4.10B), v n xy ra sm trong qu trnh pht trin phi ( giai on
khong 2.000 t bo). Khng th d on liu X t b hay X t m b bt
hot trong mt t bo no . Nhng y khng phi l trng hp cho
cc mng ngoi phi (extraembryonic membranes); tt c cc t bo ca
cc mng ny th ch c nhim sc th X ca ngi b l b bt hot
(Rastan 1994; Lee v Jaenisch 1997; Kimball 2004).
Mt s gene trn X thot khi s bt hot: Vn t ra l, vi 18
gene c pht hin trn Y cng nh X th sao? S khng c nhu cu no
cho cc con ci (females) lm bt hot mt bn sao ca cc gene gi
cn bng vi tnh hung cc con c. Th th chng qun l iu tit
vic ny ra sao vn cn cha c khm ph (Kimball 2004).
Chn on cc bt thng nhim sc th X: R rng l, s hiu
bit v hin tng ny c ng dng thc t to ln trong chn on trc
sinh hoc kim tra cc bnh tt nhng ngi trng thnh c th c lin
quan n cc t bin lch bi nhim sc th X. Chng hn, chn on
trc sinh, ngi ta s dng phng php chc i (amniocentesis), ri lm
tiu bn kim tra s bt thng nhim sc th v thit lp kiu nhn. Cng
thc tng qut cho trng hp ny l:
S nhim sc th X = s th Barr + 1
Nh vy, nhng ngi nam bnh thng v cc c th mc hi chng
Turner (XO) khng c th Barr no; nhng ngi n bnh thng v cc
c th mc hi chng Klinefelter (XXY) c mt th Barr; nhng c th
XXX c hai th Barr v.v. (xem Hnh 4.10B).
Gii thch s hnh thnh cc th khm di truyn: Vi c ch bt
hot ngu nhin ca cc nhim sc th X, cc t bo ca con ci s l th
khm di truyn (genetic mosaics) v hai nhim sc th X ca n. y l
nguyn nhn dn ti s hnh thnh mu lng "sc vn" hay tam th mo
ci (Felix catus). Ta c th hnh dung mi quan h gia kiu gene v kiu
120
hnh mo lin quan ti mt gene xc nh mu lng trn nhim sc th X

nh sau: Nu quy c allele B - mu en v allele O- mu da cam, ta c:
Ci Kiu gene
XBXB
XXO
XBXO
Kiu hnh
en
da cam
tam th
Kiu gene
Kiu hnh
XBY
XOY
en
da cam
Nh vy, cho mo c l tam th r

rng l n phi c hai nhim sc th X,
XBXOY, ngha l th d bi v nhim sc th
gii tnh. iu ny rt him khi xy ra trn
thc t. n y ta thy rng vic gii thch
s xut hin mo tam th bng c ch tng
tc gia cc gene allele theo kiu ng tri
trong nhiu ti liu trc y v c hin nay
l khng ng! cng l l do ti sao Hnh 4.11 S hnh thnh
chng ti a mc ny vo y m khng mu sc b lng mo tam
th c gii thch bng s
t n trong chng 3 (khi xem xt cc th bt hot ngu nhin ca cc
t bin lch bi) hoc sau mc II-1 ca nhim sc th X.
chng ny nh cch lm truyn thng.
3. Cc tnh trng gii hn bi gii tnh v chu nh hng ca gii tnh
Nh ni trn, thng thng cc tnh trng c s phn b khng
ng u gia hai gii tnh hoc tp trung mt gii lm ta lin tng ti
quy lut di truyn lin kt vi gii tnh do gene hoc trn X (di truyn
cho) hoc trn Y (di truyn thng). Tuy nhin, mt s tnh trng c
biu hin mt cch khc bit c hai gii nhng khng phi l lin kt vi
gii tnh. l nhng tnh trng b gii hn bi gii tnh hoc l chu nh
hng ca gii tnh.
(1) Cc tnh trng b gii hn bi gii tnh (sex-limited traits): l
nhng tnh trng ch biu hin mt gii. C nhiu tnh trng nh vy lin
quan vi cc c im sinh sn cc ng vt ci. Chng hn, kh nng
cho sa cc gia sc nh tru-b, kh nng trng gia cm v lp
chim ni chung, hoc tp tnh trng cc cn trng.
Bng 4.4 V d v tnh trng chu nh hng ca gii tnh Cu
Con c
Con ci
HH (Suffolk)
Hh (Con lai)
hh (Dorset c sng)
Khng sng
Khng sng
C sng
Khng sng
C sng
C sng
121
(2) Cc tnh trng chu nh hng ca gii tnh (sex-influenced traits):

l nhng tnh trng c xc nh bi cc gene trn nhim sc th
thng nhng li biu hin mt cch khc bit hai gii. Chng hn, cc
gene xc nh s c sng (horn) cu c biu bin mt cch khc bit
cc con c v con ci. mt s ging cu, nh ging cu Suffolk,
sng chng thy gii no c (chng c gi l cu khng sng), trong
khi cc ging khc, nh ging cu c sng Dorset (Dorset Horn), th c
hai gii u c sng mc d cc sng ca con c ln hn sng ca con
ci rt nhiu. Khi lai gia hai ging cu ny vi nhau, cc con lai thu c
l nhng th d hp t v gene H thuc nhim sc th thng (Hh); tuy
kiu gene nh nhau nhng ch c con c mi c sng, cn con ci
khng c sng (Bng 4.4). iu d chng t rng, cc c th d hp t,
chnh s c mt ca cc hormone c hoc ci xc nh pht trin sng
hay l khng pht trin sng. Ngi ta cho rng hin tng hi u sm
(premature baldness) ngi, thng xy ra trc tui 35, tun theo cng
kiu di truyn nh trng hp va xt cu; ngha l, hi u l tri
nhng ngi nam d hp t (Bb) v ln nhng ngi n d hp t (Bb).
l l do ti sao chng hi u rt him khi thy ph n.
IV. Lin kt v ti t hp ca cc gen trn mt nhim sc th

Trc khi cp vo cc khm ph ca Morgan v hin tng di
truyn lin kt rui gim, ta cn lu rng: Vo nm 1906, Batson v
Punnett nghin cu s di truyn ca cc tnh trng khc nhau cy u
ngt (sweet pea). Trong mt th nghim kim tra s di truyn ng thi
ca mu hoa v hnh dng ht phn, h thu c cc kt qu F2
khng ph hp vi t l 9:3:3:1 ca Mendel. Kt qu cc php lai (k c
quy c gene) c trnh by tm tt hnh 4.12.
Ptc
Hoa ta, ht phn di Hoa , ht phn trn
(PPLL)
(ppll)
Hoa ta, ht phn di
F1
(PpLl)
F1 (t th phn) F2
Kiu hnh
Ta, di
Ta, trn
, di
, trn
Tng
S quan st (O)
296
19
27
85
427
S k vng (E)
240,2
80,1
80,1
26,7
427,1
(O E)2/ E
13,1
46,5
35,1
127,3
2 = 222,0
Hnh 4.12 Kt qu lai hai tnh ca Bateson v Punnett u ngt.
122
R rng l t l F2 c quan st v k vng theo t l 9:3:3:1 l hon

ton khng khp nhau; nu kim tra bng phng php 2, s sai khc ny
cao mt cch ng k v khng ph hp vi gi thuyt phn ly c lp.
Hai ng c gng a n v t l 7:1:7:1 gii thch bng kiu tng
tc gene, nhng khng thnh cng. V cui cng, h a ra gi rng
bi v hai kiu hnh b m vt qu mc cho php F2, c l c mt s
ni kt gia cc allele dng b m. i vi hin tng gy nhiu ln s
phn ly c lp ny, h gi l kiu kt ni (coupling). Mt khc, h cho
rng s lng thp ca cc kiu F2 vn c mt kiu hnh tri gene ny
v mt kiu hnh ln gene kia, l do i lc m tnh t nhin ca cc
allele tri v ln, v h gi l kiu y nhau (repulsion).
1. Khm ph v s trao i cho rui gim
gii thch v mt vt l cc quan st ca Bateson v Punnett, vi
nm sau Morgan tin hnh hng lot th nghim s dng ng thi
hai gene Drosophila, m mi gene u c hai allele ln v tri (k hiu
allele da theo tn ca th t bin ln trong ting Anh nh cp). C
th k mt s th nghim m ng lm sau y: (i) mt gene kim sot
mu mt (pr: ta v pr+: di) v gene kia kim sot cnh (vg: ngn v
vg+: di bnh thng); (ii) mu mt (w: trng v w+: ) v dng cnh (m:
cnh b v m+: cnh bnh thng); hoc (iii) mu thn (e: mun v e+: xm)
v dng cnh (c: cnh cong v c+: cnh thng) v.v... By gi ta hy xt
mt trng hp quen thuc, l: gene quy nh mu sc thn (allele ln
b: en v allele tri B: xm) v gen xc nh chiu di cnh (vg: cnh ngn
v Vg: cnh di bnh thng).
Morgan cho lai gia hai dng rui thun chng thn xm, cnh di
(BBVgVg) v thn en, cnh ngn (bbvgvg), i con F1 ng thu c tt
c cc con c v ci u c thn xm, cnh di (BbVgvg). Nhng khi
em lai phn tch cc con c v ci F1, kt qu hon ton khc nhau.
Trc tin, ta xt php lai phn tch gia cc con ci xm-di F1 vi
con c en-ngn. Kt qu cc php lai ny cho i con c c bn kiu
hnh (xem hnh 4.13a), nhng vi t l quan st khc xa vi t l k vng
1:1:1:1 (xem hnh 4.13b), nh sau:
Kiu hnh
S liu quan st
S liu k vng
xm-di
en-ngn
xm-ngn
en-di
Tng
965
575
944
575
206
575
185
575
2300
2300
Cc kiu hnh b m
Cc kiu hnh ti t hp
T kt qu i con ca lai phn tch rui ci F1 cn cho thy cc kiu

hnh b m ban u l xp x nhau, chim 83% ([965 + 944]: 2300 =
123
0,83); cc kiu hnh ti t hp cng c s lng gn nh tng ng,

chim 17% ([206 + 185]: 2300 = 100% 83% = 0,17). iu ny ch c
th l gii nu nh cc gene nm trn cng nhim sc th, hay gi l lin
kt (linkage), v trong qu trnh gim phn rui ci c xy ra s trao i
cho (crosing over) hay ti t hp (reconbination) gia hai gene ny.
Tht vy, trong php lai phn tch ny, rui c en-ngn (bvg/bvg)
ch cho mt loi giao t cha c hai allele ln, bvg). T y suy ra rui ci
F1 xy ra trao i cho v cho bn loi giao t tng ng vi t l cc
kiu hnh i con: (i) Cc kiu b m (parental) mi kiu c t l trung
bnh l 41,5% (BVg = bvg = 0,415); v (ii) Cc kiu ti t hp
(recombinant) mi kiu c t l trung bnh l 8,5% (Bvg = bVg = 0,085).
Nh th, da vo thnh phn gene ca P hoc thnh phn allele ca cc
giao t chim t l cao (tc cc kiu b m) ta d dng xc nh c kiu
gene ca F1 l BVg/bvg (kiu cis).
Kiu di
en, ngn
Kiu gene b m
en-ngn
Kiu di
Kiu hnh b m
Kiu gene ti t hp
Xm-ngn
en-di
Kiu hnh ti t hp
Hnh 4.13 Kt qu ca cc php lai P v lai phn tch rui ci F1 (tri) v

gii thch bng c s t bo hc ca kt qu lai phn tch rui ci F1.
Trong th nghim th hai, Morgan lai hai kiu gene, mi kiu l

ng hp v allele tri mt gene ny v ng hp v allele ln mt
gene kia (BBvgvg bbVgVg). Cc rui F1 d hp t kp (BbVgvg) sau
c lai vi dng kim tra bbvgvg. Kt qu ca php lai ny, so vi th
nghim trc, cho thy i con c s o ngc gia nhm cc kiu b
m v nhm cc kiu ti t hp; ngha l, s lng i con mang cc tnh
trng tri n (Bvg/ bvg v bVg/ bvg) cao hn nhiu so vi k vng, trong
khi s lng i con mang cc tnh trng tri kp (BVg/bvg) v cc tnh
trng ln kp (bvg/ bvg) thp hn nhiu so vi k vng. Nh vy, F1 c
kiu gene Bvg/bVg (kiu trans).
124
Ghi nh:
(1) S kin trao i cho thng c ch ra trn cc s bng mt
'du cho' () ni gia cc nhim sc th tng ng (hnh 4.14).
(2) i vi trng hp d hp t kp v hai cp gen lin kt, c hai
AB
Ab
cch sp xp cc allele trn mt cp nhim sc th:
v
, m c th
ab
aB
vit n gin l: AB/ab v Ab/aB.
- Cch sp xp cc allele trong hai allele tri trn mt nhim sc
th v hai allele ln trn chic kia, AB/ab, c gi l kiu kt ni
(coupling) hay kiu u (cis). Vi kiu gene ny, AB v ab l cc giao t
thuc kiu cha m, cn Ab v aB l cc giao t thuc kiu ti t hp.
- Cch sp xp cc allele trong mi nhim sc th mang mt allele
tri v mt allele ln sao cho trong th d hp kp chng cc v tr cho
nhau, Ab/aB, c gi l kiu y nhau (repulsion) hay kiu lch (trans).
Vi kiu gene ny, Ab v aB l cc giao t thuc kiu cha m, cn AB v
ab l cc giao t thuc kiu ti t hp.
Hnh 4.14 M hnh mt trao i cho n (tri) v cch biu din n.
(3) S ti t hp ca cc gene lin kt kiu u (cis) cng nh kiu

cho (trans) t c hai php lai phn tch ni trn v cc php lai thun
nghch ni chung u xy ra vi tn s gn nh nhau;
(4) Tng t l ca cc kiu ti t hp i con ca php lai phn tch
c gi l tn s ti t hp, v tn s ny c trng cho mi cp gene
ring bit (nh s tho lun di y).
2. Lin kt gene hon ton (hay gim phn khng c trao i cho)
By gi ta tr li th nghim u tin ca Morgan. Khi thc hin php
lai phn tch gia cc con c xm-di F1 vi con ci en-ngn, i con
ch c hai kiu hnh xm-di v en-ngn vi t l xp x 1:1, ch khng
phi bn kiu vi t l u nhau nh d on. iu ny chng t rui c
F1 ch cho hai loi giao t vi t l tng ng ( BVg = bvg = 50%),
tng ng vi hai kiu hnh i con (v rui ci en-ngn ch cho mt loi
giao t cha hai allele ln, bvg); ngha l cc gene ny cng nm trn mt
nhim sc th v gia chng c s lin kt hon ton (complete linkage).
Ni cch khc, ti t hp khng xy ra rui gim c.
125
Gim phn m khng c bt k s trao i cho no ch xy ra mt

s t loi. cc sinh vt ny, ti k gia I cc nhim sc th tng ng
nm dc bn nhau mt phng ca thoi. Chng phn tch theo cch thng
thng k sau I, v gim phn tin hnh mt cch bnh thng sau .
Kiu gim phn ny thy c mt vi cn trng, k c cc con c ca
rui gim, v mt s thc vt c hoa. tt c cc loi cn li c t nht
mt trao i cho c hnh thnh trong mi th lng tr k trc I.
Tm li, tt c cc loi sinh sn hu tnh, trong qu trnh gim phn
c th khng xy ra trao i cho hoc c t nht mt trao i cho c
hnh thnh trong mi th lng tr k trc I. i vi hai cp gene bt
k trn mt cp nhim sc th tng ng, cc sn phm tng ng c
to thnh trong cc giao t c minh ha hnh 4.15 di y.
A. Khng trao i cho
B. C trao i cho
Hnh 4.15 Gim phn khng c trao i cho (A) v c mt trao i cho
n (B), v cc sn phm c to thnh i vi hai cp gene bt k trn
mt cp nhim sc th tng ng.
V. Trao i cho v lp bn di truyn

1. Tn s ti t hp
S trao i cho l mt qu trnh trao i gia cc nhim sc th trong
gim phn (kt hp vi s hnh thnh giao t mt cch bnh thng) cho
ra cc t hp tnh trng mi, gi l cc bin d t hp (xem hnh 4.13). Tn
s ti t hp (frequency of recombination or rate of recombination), cn
c gi l tr s trao i cho (cross over value), k hiu l r, c tnh
bng t l phn trm ca cc th ti t hp sinh ra trong mt php lai phn
tch, theo cng thc sau:
n
r = 100
m
126
trong : n - s lng cc c th ti t hp c sinh ra, v m - tng s c

th ca i con ca php lai phn tch; v r - tn s ti t hp (thng gi
l tn s hon v gene), l mt s hu t tha mn min gii hn [0; 0,5],
c th biu din bng s thp phn hoc phn trm.
cc sinh vt m ch s trao i cho c nghin cu rng ri,
chng hn nh ng v rui gim, t l ca cc th ti t hp sinh ra trong
mt php lai c th l kh n nh. Tuy nhin, cc t l ny l khc nhau
i vi cc gene khc nhau trn cng mt nhim sc th. iu ny c
gii thch da trn c s rng mi mt gene c mt v tr c nh (tc
locus ca n) trn mt nhim sc th c th, v rng s trao i cho c
th xy ra gia cc gene nm xa nhau. Vi v d v hai gene b v vg rui
gim ni trn, ta c th ni rng cc locus ny nm kh gn nhau, bi v c
rt t cc th ti t hp c to ra. p dng cng thc tnh tn s ti t
206 + 185
hp trn, ta tnh c: r =
100 = 17% . T y suy ra t l
2300
k vng ca cc loi giao t ti t hp v khng ti t hp (dng b m):
giao t kiu ti t hp Bvg = bVg = 17%: 2 = 8,5%
BVg = bvg = (100% 17%): 2 = 41,5%
giao t kiu b m
Mt cch tng qut, da theo tn s ti t hp (r), ta c th biu din t
l ca cc loi giao t ti t hp v khng ti t hp i vi hai kiu gene
d hp t u (AB/ab) v d hp t cho (Ab/aB) bng 4.5.
Bng 4.5 T l ca cc loi giao t
Giao t
AB
ab
Ab
aB
Tng
Kiu gene b m
AB/ab
(1 r)
(1 r)
r
r
1
Ab/aB
r
r
(1 r)
(1 r)
1
By gi ta cp mt t v mi quan h gia hai gene khng allele

trong qu trnh gim phn to giao t, m ta c th kim tra bng phng
php kinh in c p dng trong nghin cu di truyn hc l lai phn
tch. Ngoi ra, cng c th s dng cc phng php khc, khng c
ph bin lm hoc kh phc tp nh l t th phn hoc tp giao.
i vi hai gene trng thi d hp t kp quy nh hai cp tnh
trng tng phn khc nhau, trong mt php lai phn tch:
127
(i) Nu nh hai gene nm trn hai nhim sc th khc nhau, s c bn

kiu giao t (hay kiu hnh) c to thnh vi t l ngang nhau;
(ii) Nu nh hai gene lin kt hon ton trn mt nhim sc th, ch c
th to ra hai loi giao t (hay kiu hnh) vi t l ngang nhau (r = 0);
(iii) Nu nh hai gene lin kt khng hon ton trn mt nhim sc
th, c th to ra bn loi giao t (hay kiu hnh) thuc hai nhm, trong
cc kiu giao t ti t hp mi kiu chim t l bng r/2, v cc kiu giao
t b m mi kiu chim t l bng (1 r)/2;
(iv) Tn s ti t hp (r) bin thin trong khong 0 0,5; thng
thng r thp hn 50%, ph thuc vo khong cch vt l gia hai gene
trn nhim sc th. Trong cc trng hp cc oan, tr s r c th bng
zero (r = 0), nu nh hai gene lin kt hon ton hoc nm gn st nhau; v
tr s r ny cng c th t cc i, ngha l r = 0,5 hay 50%, trong trng
hp cc gene nm cch nhau hn 50 n v bn (nh chng ta s cp
ngay di y) hay ni cch khc, tt c cc t bo sinh giao t tri qua
gim phn u xy ra trao i cho gia hai gene c xt n. Khi t
l cc giao t (hay t l phn ly kiu hnh) trng vi trng hp cc gene
phn ly c lp. Tuy nhin, rt him khi xy ra nh vy.
2. Bn di truyn
Vic thit lp bn gene ca cc nhim sc th ln u tin c p
dng rui gim Drosophila, c xut vo nm 1913 bi Alfred
Sturtevant, mt mn ca Morgan. Theo ng, ta c th da vo cc tn
s ti t hp ca cc gene thu c trong cc php lai phn tch m t
mi quan h vt l ca cc gene trn mt nhim sc th theo trt t tuyn
tnh, gi l bn lin kt (linkage map) hay bn di truyn (genetic
map). Khong cch bn (map distance) gia hai gene, v d b v vg l
17%, c coi l cch nhau 17 n v bn (map unit; vit tt l: m.u.);
hay ni cch khc, 1 n v bn l 1% ti t hp. Cc nghin cu v
sau cho thy rng khong cch di truyn c o bng phng php thng
k (tc t l phn trm ti t hp, do Morgan v Sturtevant xut) ni
chung l ging vi cc khong cch trn nhim sc th o c v mt t
bo hc hay ha sinh hc.
Nguyn tc chung ca vic xy dng bn nhim sc th mt loi
no , theo Morgan v cc ng s ca ng, c th tm tt th ny:
(1) Xc lp s nhm lin kt (s nhim sc th n bi) ca loi. iu
ny c th tin hnh bng cch thc hin hng lot cc php lai c th
c xc nh cc mi quan h (c lp v lin kt) trong s hng lot
gene, kt hp vi cc nghin cu t bo hc (m s lng nhim sc th).
128
(2) Xc nh thnh phn gene ca mi mt nhm lin kt (da vo cc

kt qu lai khc nhau).
(3) Xc nh v tr, trt t v khong cch gia cc gene trn mi nhm
lin kt. Nguyn tc chung l, gia cc gene lin kt c tn s ti t hp
cng thp chng no chng t chng nm cng gn nhau chng y; theo
chui suy lun ta c th bit c v tr ca mt gene khi u v cc
gene k tip theo chiu dc trn mt nhim sc th, v t gene khi u
nm u mt ca vai ngn ng vi v tr zero (0,0); sau dng phng
php cng dn biu din v tr v khong cch trn bn ca cc gene
k tip vi so vi gene u mt ny. Khi ta c c bn ca mt
nhm lin kt. Ta c th hnh dung n nh mt on thng nm ngang c
nhiu vch ch ra trt t thng hng ca cc gene, mi vch ng vi mt
locus-gene c th (pha trn vch l k hiu v c th c tn y ca th
t bin gene v pha di vch l v tr trn bn ca gene so vi
gene khi u, c ghi bng mt con s c th; hnh 4.17a). Nu ta dng
ng bn ln, theo nguyn tc, k hiu cc gen s nm v pha bn phi
v khong cch bn ca cc gene nm pha bn tri (hnh 4.17b).
y, c mt s im cn lu : (i) chnh xc ca bt k bn
lin kt no c thit lp trc y u c th thay i v ngy cng
chnh xc hn; l do cc pht hin b sung nhng gene mi nm trung
gian gia cc gene c nh v cng vi cc tn s ti t hp ca
chng; (ii) Ring rui gim, nhim sc th X c Morgan gn cho s I,
k n l cc s II, III v IV tng ng vi s nh dn v kch thc.
Ngy nay, mc d h thng nh s nhim sc th c thay i, song i
vi rui gim vn c gi nguyn biu th lng tn knh i vi
Morgan - ngi sng lp thuyt di truyn nhim sc th; v (3) Morgan
ci tin cch lp bn vn cng knh phc tp ni trn bng phng
php lai phn tch ba im (nh s c tho lun di y).
Bng 4.6 Tn s ti t hp ca nm cp gene lin kt-X
Cc gen
Tn s ti t hp
thn vng (y) mt trng (w)

thn vng (y) mt ti (v)
214/21.736 = 0,010
1.464/4.551= 0,322
mt trng (w) mt ti (v)

mt ti (v) cnh b (m)
471/1.584 = 0,297
17/573
= 0,030
mt trng (w) cnh b (m)
2.062/6.116 = 0,337
mt trng (w) cnh khng pht trin (r)
406/898
= 0,452
mt ti (v) cnh khng pht trin (r)
109/405
= 0,269
129
Chng hn, bng cch s dng s liu bng 4.6, Sturtevant xc

nh cc mi quan h vt l ca nm gene ny v gi rng chng xp
theo mt ng thng. Cch lm nh sau: (1) Hai gene y v w c tn s
nh nht (ry-w = 1%) nn nm gn nhau. (2) v rw-v = 29,7% < ry-v = 32,2%
trt t ba gene ny phi l y-w-v. (3) Gene gn nht vi v l m (rv-m =
3%), m rw-m rw-v + rv-m m phi nm bn phi v. (4) rv-r = 26,9% < rw-r
= 45,2% r phi nm bn phi v v m. Vy, trt t ca nm gene lin
kt trn X l: y-w-v-m-r. T y, Sturtevant xy dng nn mt bn bt
u bng y v tr 0,0 v pha bn tri v s dng cc tn s ti t hp
gia cc gene k nhau biu th v tr ca chng trn bn ng vi
tng con s c th. Theo , w v tr l 1,0, v v tr 30,7 (= 1,0 + 29,7),
m v tr 33,7 (= 30,7 + 3,0), v r v tr 57,6 (= 30,7 + 26,9). So vi bn
hin nay, v tr nm gene trn bn ca Sturtevant c hi khc mt
cht bi v c nhiu gene trung gian c pht hin b sung (hnh 4.16).
yw

Sturtevant 0,0 1,0
Hin nay 0,0 1,5
30,7 33,7
33,0 36,1
r
57,6
54,5
Tm ng
66,7
Hnh 4.16 Bn Sturtevant v nm gene lin kt-X v so vi hin nay.
Di y cho thy bn ca nhim sc th s 2 rui gim (hnh

4.17a) v nhim sc th s 9 ng (hnh 4.17b) vi nhng gene chnh yu.
Chng hn, trn hnh 4.17a, hnh ng gia tng trng cho nhim sc
th s 2 rui gim ch ra v tr ca su gene; pha trn l cc kiu hnh t
bin, v pha di l cc kiu hnh bnh thng. T tri sang: v tr 0 gene al (aristaless antenna) ch t bin ru ngn i vi ru di bnh
thng; v tr 13 - gene dp (dumpy wings) ch t bin cnh xn vi cnh
di; v tr 31 - gene d (dachs) ch t bin chn ngn vi chn di), v tr
54,5 - gene pr (purple eyes) ch t bin mt ta vi mt ), v tr 67,0
- gene vg (vestigial) ch t bin cnh ngn vi cnh di), v tr 104 - gene
bw (brown eyes) ch t bin mt nu vi mt ).
Cn lu rng, ngy nay, sau khi nh v bn cc gene xc nh
by tnh trng m Mendel nghin cu u H Lan, ngi ta khng
khi ngc nhin ti sao Mendel li khng quan st hin tng lin kt
trong cc php lai hai tnh ca mnh. Mc d Mendel chn ra by tnh
trng v c by nhim sc th u H Lan (2n = 14), hai trong s cc
tnh trng ng nghin cu c xc nh bi cc gene trn nhim sc th
s 1 v ba tnh trng c xc nh bi cc gene trn nhim sc th s 4
(bng 4.7). Thc ra, Mendel ch chn nghin cu mt vi tnh trng v c
l, tht may mn l ng khng quan st thy cc kiu m khc vi k
130
vng v s phn ly c lp. Chnh iu ny lm nn s nht qun hon

ton v ht sc r rng, n gin trong cc kt qu m ng cng b.
Hnh 4.17 Bn nhim sc th s 2 ca rui gim (bn tri) v nhim sc

th s 9 ca ng (bn phi).
Qu ng nh Watson vit trong Li ni u cun "Chui xon kp

- Hi k v vic pht minh ra cu trc ca DNA" ca mnh, rng: "Cch
gii quyt ng khng nhng phi p m cn phi n gin" (Watson
1968). Chn l bao gi cng gin d nhng gin d cha hn l chn l;
chn l bao gi cng p nhng p th cha l chn l. Tuy nhin,
nhn chn c ci gin d, ci p ch thc trong cc khm ph ca
Mendel, nh chng ta u bit, nhn loi phi mt chng 35 nm!
Bng 4.7 Cc v tr nhim sc th i vi by tnh trng u H Lan
Tnh trng
Dng ht
Mu sc ht
Mu sc qu
Kt cu qu
Mu sc hoa
V tr hoa
Chiu cao cy
Kiu hnh
trn-nhn
vng-xanh
xanh-vng
trn-nhn
tm-trng
trc-nh
cao-thp
Allele
R-r
I-i
Gp-gp
V-v
A-a
Fa-fa
Le-le
Nhim sc th
7
1
5
4
1
4
4
131
3. Trao i cho bn si
Hc thuyt ca Morgan v cc gene lin kt v trao i cho c
ng h rng ri bi nhiu s liu. Tuy nhin, cn cha tht s r rng
ch, liu s ti t hp xy ra gia cc nhim sc th trc khi chng ti
bn ( giai an hai si) hay sau ti bn ( giai on bn si). Nu nh
trao i cho xy ra trc khi ti bn th tt c bn chromatid s l cc th
ti t hp, trong khi nu xy ra sau ti bn th ch c hai trong bn
chromatid s l cc th ti t hp (xem hnh 4.15).
phn bit gia cc dng bin i ny, phi cn ti mt h thng di
truyn trong tt c cc sn phm di truyn t gim phn phi c xc
nh. Bng chng u tin v s trao i cho sau ti bn nhim sc th c
c t vic nghin cu rui gim, trong hai nhim sc th X ca
rui gim ci dnh nhau tm ng ca n v to thnh mt nhim sc th
sai hnh, gi l nhim sc th X-dnh (attached-X). Kt qu ca s dnh
ny l, t con ci c nhim sc th X-dnh v mt nhim sc th Y tch
ring (X-XY) s cho ra cc giao t hoc cha hai nhim sc th X hoc
khng c X (ch c mt Y). V d, php lai trong c hai nhim sc th
X u c mang allele kiu di ti locus mt trng c cho hnh 4.18.
Cc con ci X-XY vi allele kiu di trn c hai X (X+-X+Y) c cho lai
vi cc con c mt trng "bnh thng" (XwY). Cc c th con sng c
u ging vi b m, trong khi cc con rui gim YY cht ht v XXX thng l b cht.
X+-X+Y
XwY
(ci mt )
(c mt trng)
+
+
(Xw : Y)
Giao t
(X -X : Y)
: X+-X+Y
: XwY
: YY
F1 Kiu gene = X+-X+Xw
Kiu hnh = (thng cht) : (ci mt ) : (c mt trng) : (cht)
Hnh 4.18 Mt php lai gia rui gim ci kiu di X-dnh v con c mt
trng. y i con sng st th ging ht cc b m chng.
Khi cc allele trn hai nhim sc th X-dnh l khc nhau th s trao

i cho hai si v bn si l c th phn bit c. Chng hn, hnh
4.19 cho thy th t bin mt thi Bar lm gim s lng cc mt b t
con s bnh thng khong 780 kiu di (con ci B+B+ hoc con c
B+Y) xung cn khong 360 cc th d hp (con ci BB+) v khong 70
cc th ng hp (con ci BB hoc con c BY).
Bng cc thc nghim cho thy rng: (i) Trong trng hp khng xy
ra trao i cho, tt c cc giao t mang cc nhim sc th X th c dng
132
X-dnh trng thi d hp v do c kiu hnh mt Bar d hp. (ii) Nu

trao i cho xy ra giai on hai si th s c dnh lu ti c hai si. V
vy, khi ti bn xy ra sau , tt c cc giao t s li l d hp. Ni cch
khc, cc kt qu quan st c trong c hai trng hp khng c trao i
cho v trao i cho hai si l nh nhau.
(a)
(b)
Hnh 4.19 (a) Cc kiu hnh di, mt Bar d hp v ng hp (ultraBar); v

(b) Cc kiu bng tng ng c mt, hai v ba bn sao ca bng 16A.
Ti t hp giai on bn si sinh ra cc kt qu khc nhau i con.

Trong trng hp ny, ch c hai trong bn si tham gia vo ti t hp, v
vy s sinh ra cc kiu mi. Vi ti t hp giai an bn si, c kiu di
ln kiu ng hp BB s c to ra. Trn thc t, iu ny c quan st
trong cc th nghim, ch ra rng s ti t hp xy ra sau khi ti bn ngha l, trao i cho phi xy ra gai on bn si (xem hnh 4.15).
Chng ta s cp tr li bng chng b sung v trao i cho bn si
vi nm Neurospora trong phn sau (mc VII).
S lc v trao i cho phc (multiple crossing over)
Trn thc t, khi hai gene nm xa nhau trn mt nhim sc th, gia
chng c th xy ra nhiu trao i cho trong mt ln gim phn v iu
ny gy ra nhng rc ri trong vic tnh ton, gii thch cc s liu ti t
hp v lp bn da trn cc s liu ny. Trn hnh 4.20 cho thy trao
i cho kp giai on bn si c th xy ra theo nhiu cch khc nhau.
Chng hn, hnh 4.20a cho thy trao i cho kp xy ra gia hai cp gene
Aa v Bb nhng cc nhim sc th ny khng ti t hp i vi cc allele
ca hai gene, v do khng th phn bit c vi cc nhim sc th
khng trao i cho v mt di truyn. Kt qu l cho ra ch hai loi giao t
vi t l ngang nhau (AB = ab) ging nh trng hp khng trao i cho
133
(hnh 4.15A), thay v cho bn loi giao t thuc hai kiu (hnh 4.15B).
Hin tng ny lm cho gi tr ti t hp nhn c s thp hn tn s
trao i cho thc v nh hng ti khong cch bn gia cc gene.
(a)
(b)
Hnh 4.20 (a) Hai trao i cho n xy ra vng gia hai gene A v B, v
kt qu l sinh ra c bn loi giao t khng ti t hp i vi hai gene ny,
ngha l khng pht hin c th trao i cho kp no. (b) Trao i cho
n v cc dng trao i cho kp lin quan n hai, ba v c bn si c th
xy ra trong mt cp nhim sc th tng ng.
Nh ni, tn s ti t hp cc i gia hai gene bt k trn mt cp

nhim sc th tng ng l 50%. iu ny ch c th xy ra khi hai gene
nm cch xa nhau ti mc t nht c mt on trao i cho hu nh lc
no cng xy ra gia chng. Trn hnh 4.15B ta thy r rng, c mt trao
i cho n trong mi ln gim phn s cho ra mt na s sn phm c
cc t hp ging b m v na kia l cc sn phm c ti t hp gene.
Trn hnh 4.20b cng cho thy khi xy ra hai trao i cho n m c
mt chromatid chung hay trao i cho kp lin quan ba si (hai hnh u
ca hng di), th kt qu s khng khc vi kt qu ca trao i cho
n nh hnh 4.15B. Mt kh nng khc, l trao i cho kp lin
quan c bn si (hnh 4.20b, xem hnh cui ca hng di), trong s
trao i cho th hai xy ra gia hai chromatid ( ngoi) khc vi hai
chromatid tham gia vo trao i cho th nht ( trong). Trong trng hp
ny, tt c cc sn phm u c ti t hp. Nu cc chromatid tham gia
vo hai trao i cho n mt cch ngu nhin th t l k vng ca ba
kiu trao i cho kp s tng ng vi t l : : . iu c ngha
l trung bnh s c hai trong bn sn phm ca gim phn l c ti t hp:
134
()(0) + ()(2) + ()(4) = 2. T l ny r rng l ging nh khi mt trao

i cho n m lc no cng xy ra gia hai gene.
Thc ra, nh s cp di y, trao i cho kp c th pht hin
c trong cc th nghim ti t hp s dng ba gene, gi l lai ba im.
VI. Lp bn gene t cc php lai phn tch ba im

1. Trao i cho kp vi vic xc nh trt t v khong cch cc gene
Gi s ta c ba gene lin kt A, B v C cn lp bn . Theo l thuyt,
c th c ba cch sp xp khc nhau ty vo v tr gene gia, l: (i)
A-B-C; (ii) A-C-B; v (iii) B-A-C. Tuy nhin, trong trng hp cha bit
chc v s lin kt ca ba gene, v gi s ta xc nh c tn s ti t
hp gia hai gene A v B l 15% v gia hai gene B v C l 20%. Theo
suy lun, ta bit rng ba gene ny cng nhm lin kt; v theo nguyn tc,
chng c th lin kt vi nhau theo mt trong hai cch: (i) A-B-C; hoc
(ii) B-A-C. Trong trng hp ny, ta cn phi tin hnh mt php lai phn
tch gia A v C xem liu tn s ti t hp l 35% hay 5%. Nh vy,
xc nh c v tr tng i ca ba gene ta phi tin hnh ba php lai
phn tch ring bit. Trong khi , nu da vo kh nng xy ra mt trao
i cho kp hay l hai trao i cho n ng thi (trong trng hp ba
gene khong cch ln), ta ch cn thc hin mt php lai phn tch ba
im (three-point testcross) l . iu c ngha l, vic lp bn ba
gene tr nn gn nh, khng cn cng knh phc tp nh trc na.
(a)
(b)
Hnh 4.21 (a) Mt trao i cho kp, v (b) cc sn phm to thnh.
Tht vy, theo l thuyt xc sut ca cc s kin ngu nhin, mt khi

trao i cho kp xy ra ( mt s t bo ny), th cc trao i cho n
ring r (d nhin l xy ra cc nhm t bo khc) tt yu phi xy ra v
c cc tn s cao hn hn tn s trao i cho kp. Trong trng hp ,
i con ca php lai phn tch thu c (nu y ) s c tm kiu hnh
thuc bn nhm khc nhau: Trc ht l cc kiu cha m vi tn s cao
nht; k n l cc kiu trao i cho n khc nhau; v cui cng l cc
kiu trao i cho kp vi tn s thp nht. V theo nguyn tc, c hai
kiu hnh ca mi nhm s c s lng tng ng nhau. Trn hnh 4.21
cho thy mt trao i cho kp xy ra on cha gene b (nm gia a v
135
c), v kt qu l cho ra bn sn phm gm hai kiu cha m (abc v + + +)

v hai kiu ti t hp i vi gene b (a + c v + b +). Vi kt qu ny ta d
dng xc nh gene gia v n l sn phm ca trao i cho kp.
By gi ta hy tm hiu hai v d kinh in v lai phn tch ba im,
mt th nghim rui gim v mt th nghim chn ging ng.
V d 1: Trong th nghim s dng li ba gene lin kt-X rui gim
(y, w v m), sau khi thu c cc con ci F1 d hp t v ba cp gen,
Morgan cho chng lai tr li vi con c dng kim tra (hnh 4.22). Kt
qu phn tch cho thy cc con ci F1 cho tm loi giao t (tc tm kiu
hnh i con ca n), hai trong s l cc kiu giao t b m v su
kiu cn li l cc giao t ti t hp.
Theo s trnh by trn, ta c th tin hnh phn loi v tnh tn s
ca mi kiu giao t da vo s lng cc kiu hnh thng k c (hnh
4.22) ri v bn cho ba gene ny, theo cc bc chung nht nh sau:
P
+++/+++ ywm/Y
+++/ywm
( F1)
Kiu b m (khng ti t hp)

Kiu ti t hp n m vi w
Kiu ti t hp n y vi w
Kiu ti t hp kp w vi y v m
Tng
ywm/Y
( dng kim tra)
Giao t
+++
ywm
++m
yw+
y++
+wm
+w+
y+m
S lng
3.501
3.471
1.754
1.700
28
32
6
3
10.495
Tn s
0,664
0,329
0,0057
0,00086
1,0
Hnh 4.22 Mt php lai phn tch cc rui gim ci d hp t v ba gene

lin kt -X (c cho sn s lng v tn s ca cc kiu khc nhau i con).
Bc 1: Xc nh thnh phn gene tri ln trong nhm lin kt (da

vo cc kiu giao t b m, tc hai kiu hnh c s lng nhiu nht).
y l y w m v + + + ( bit trc).
Bc 2: Xc nh v tr gene gia. Cn c vo hai kiu hnh c s
136
lng t nht suy ra y l sn phm ca trao i cho kp (Lu : trn

thc t, c th ch xut hin mt kiu hnh c th l do s lng cha
ln hoc do cc gene nm kh gn nhau nn gy nhiu, nh s tho lun
phn sau). Qua so snh thnh phn gene ca cc kiu ti t hp kp vi
cc kiu b m cho php tm ra gene thay i v tr chnh l gene gia.
Trong v d ny, gene gia l w. Vy trt t ba gene l y-w-m, v kiu
gene ca con ci F1 l: + + + / y w m. Khi bit c gene gia, ta d
dng xc nh c cc kiu trao i cho n bng cch sp xp li trt
t gene cc kiu giao t ri so snh vi cc kiu b m tm ra gene c
s thay i v tr. V d, vi hai kiu giao t + + m v y w +, v m i ch
nn y l kt qu ca trao i cho n gia w v m. Vy hai kiu cn li
l do trao i cho n gia y v w.
Bc 3: Tnh khong cch gia cc gene. tm khong cch gia
cc gene c th tin hnh theo mt trong hai cch sau:
(i) Tnh trc tip da vo s lng ca cc kiu ti t hp. Theo
nguyn tc, khong cch ca hai gene nm k nhau th bng s lng c
th ca cc kiu ti t hp gia hai gene cng vi s lng c th ca
cc kiu ti t hp kp ri chia cho tng s c th i con. V khong
cch gia hai gene u mt th bng tng cc khong cch ca cc gene
nm trong n. C th, khong cch y v w = (28 + 32 + 6 = 3) / 10.495 =
0,0066. Tng t, ta tnh c khong cch hai gene w v m = (1.754 +
1.700 + 6 = 3) / 10.495 = 0,330. Khi khong cch bn gia y v m =
0,0066 + 0,330 = 0,3366.
(ii) Tnh gin tip thng qua cc tn s kiu hnh thuc cc nhm khc
nhau (xem hnh 4.22). Khi c c cc tn s ny ri, ta tnh khong
cch gia hai gene k nhau bng cch cng tn s trao i cho n thc
t ca hai gene vi tn s trao i cho kp thc t. V d, khong cch
hai gene y v w = 0,0057 + 0,00086 = 0,0066; v khong cch hai gene w
v m = 0,329 + 0,00086 = 0,330. Khi khong cch y v m l 0,3366
(Cng c th tnh khong cch y v m bng cch cng hai tn s trao i
cho n thc t; ngha l bng 0,0057 + 0,329 = 0,335. Con s ny c hi
khc mt cht so vi con s tnh c trn. Tuy nhin, trn thc t, vic
tnh khong cch hai gene u mt l khng cn thit).
Bc 4: V bn gene. Bn hy t v bn cho ba gene ny.
V d 2: Tm tt kt qu th nghim lai phn tch ba gene trn trn
mt nhim sc th ng (Zea mays). Cc allele ln c s dng trong
php lai mt c th F1 d hp t ba cp gene (Lz Gl Su / lz gl su) ny l: lz
(tp tnh mc b lan), gl (l bng), v su (ni nh ng). Php lai v kt
qu c cho bng 4.8.
137
(F1 em lai)
(dng kim tra)
Bng 4.8 Kt qu i con ca php lai phn tch ba im ng

Kiu hnh i con
ca php lai phn tch
bnh thng (kiu di)
mc b lan
l bng
ni nh ng
mc b lan, l bng
mc b lan, ni nh ng
l bng, ni nh ng
mc b lan, l bng, ni nh ng
Kiu gene giao t t F1

Lz Gl Su
lz Gl Su
Lz gl Su
Lz Gl su
lz gl Su
lz Gl su
Lz gl su
lz gl su
Tng
S lng
286
33
59
4
2
44
40
272
740
Bng phng php trn y, ta xc nh c:

(i) Thnh phn nhm gene lin kt phi l: Lz Gl Su ( bit trc)
(ii) Gene gia l Su, v trt t ba gene: Lz-Su-Gl
(iii) Khong cch gia Lz v Su = (40 + 33 + 4 + 2)/ 740 = 0,107 hay
10,7%; gia Su v Gl = (59 + 44 + 4 + 2)/ 740 = 0,148 hay 14,8%.
(iv) Bn gene v s trao i cho kp c minh ha nh sau:
2. nhiu (interference) v h s trng hp (coefficient of coincidence)

V thc cht, ti t hp hay trao i cho l s kin mang tnh xc sut
cho nn iu quan trng cn bit l xem liu cc trao i cho n ny l
c lp vi nhau hay c nh hng no ln nhau hay khng. Nu cc
s kin ti trao i cho khc nhau l c lp, th xc sut ca hai s kin
ng thi nh th xy ra trong cng giao t s bng tch xc sut ca cc
s kin ring r. Khi , tn s trao i cho kp k vng t v d 1 s
bng 0,330 0,0066 = 0,00218. Trong khi , tn s trao i cho kp
138
quan st c l 0,00086; r rng l thp hn t l c k vng. ng ra,

theo l thuyt, s c th trao i cho kp xut hin phi bng 0,00218
10495 23 (con s thc t xut hin t hn 23 9 = 14 c th).
S chnh lch nh th ni chung rt ph bin cc sinh vt, v n
c coi l hin tng nhiu (interference); ngha l s xut hin mt trao
i cho mt vng nhim sc th lm gim xc sut xy ra trao i cho
vng th hai ln cn n.
m t s khc nhau gia cc s lng trao i cho quan st v k
vng , ln u tin H.J. Muller a ra mt phng php chun cho s
tnh ton ny. Theo , h s trng hp (coefficient of coincidence) c
o bng s lng hay tn s cc th ti t hp kp quan st (O: observed)
chia cho s lng hay tn s k vng tng ng (E: expected); v nu ta
k hiu h s trng hp l C, th C = O/E; trong : 0 C 1. Tr s ny
l mt tiu chun cho php o mc nhiu I (interference) ca mt trao
i cho ny ln mt trao i cho khc. Cng thc dng tnh nhiu
ny nh sau:
I=1C
trong 0 I 1. T v d 1 trn, ta tnh c C = 0,00086/0,00218 =
0,3945; iu ny c ngha l s lng trao i cho kp thc t xy ra
ch bng 39,45% con s l thuyt. Vy I = 1 0,3945 = 0,6055. Tr s ny
cho thy mc nhiu cao ng k.
R rng hai i lng ny l nghch nhau v tng ca chng bng n
v (I + C = 1). Nu I = 1, lc C = 0; iu c ngha l, hin tng
nhiu tng dn ln khi m khong cch hai gene pha bn ngoi cng ngn
li, cho ti khi trao i cho kp khng th xy ra ti mt im gii hn
(nhiu hon ton) v h s ph hp bng zero. nhiu sinh vt khong
cch ny l khong 10 n v bn . Ngc li, nu I = 0, th C = 1;
ngha l khi cc gene nm rt xa nhau n ni cc trao i cho ca chng
khng nh hng g ln nhau (hon ton khng nhiu), th hin tng
nhiu bin mt v h s ph hp bng 1. Cc thc nghim cho thy I = 0
khi tng khong cch gia cc gene ln hn chng 45 n v bn .
Mt l thuyt gii thch tn s trao i cho kp thp him l ch
tr s nhiu cao i vi cc gene lin kt cht r rng l c lin quan vi
hin tng "x cng", khng th vn xon v mt vt l ca cc chromatid
trong mt vng rt ngn. Tuy nhin, hin tng nhiu c th xy ra cc
gene cch xa nhau ti 30 n v bn ; iu ny ch ra rng cc nhn t
khc cng c tm quan trng khng km. Tht l th v, cc tm ng ca
cc nhim sc th tm gia rui gim (v c l c nhiu sinh vt khc)
139
hot ng nh l cc vt cn i vi hin tng nhiu. Ni cch khc, s

trao i cho mt vai ca nhim sc th tm gia khng gy hiu qu c
ch ln s trao i cho vai kia.
VII. Lp bn bng phn tch b bn (tetrad analysis)

Vic khng nh trao i cho bn si cng thu c Neurospora
crassa, mt loi vi nm c nghin cu nhiu trong di truyn hc, c cc
sn phm ca gim phn cha ng trong mt dy cc bo t c trt t
c sp xp theo kiu thng hng (hnh 4.23). Mt nhn hp t cha
trong mt cu trc dng ti gi l nang (ascus), tri qua gim phn hu
nh ngay sau khi n va c to thnh. Bn nhn sinh ra t gim phn
nm trong mt ci nang theo mt trt t thng hng, v mi nhn ny li
tri qua mt ln nguyn phn na to thnh hai bo t nang (ascospores)
nm k nhau v ging ht nhau v mt di truyn. Do , mi nang trng
thnh c cha tm bo t nang theo bn cp, mi cp biu th mt sn
phm ca gim phn. Lc ny, ta c th tch cc bo t nang theo trnh t
ca mi nang v cho ny mm trong cc ng nui cy ring xc nh
cc kiu gene ca chng.
Bo t v tnh
Dung hp
Sinh trng
sinh dng
Sinh trng
sinh dng
Hp t
Bo t v tnh
(bo t dnh)
Gim
phn I
Gim
phn II
Ny mm
Nguyn phn
Nui cy
Ny mm
Nang cha 8 bo t
Hnh 4.23 Vng i ca Neurospora crassa.

Ch thch: Cc bo t sp xp thnh mt dy thng hng trong nang sao cho mi
mt na bt ngun t cc th phn ly gim phn I. Mi mt phn t bt ngun
t cc chromatid kt hp vi mt tm ng c th.
S sp xp c trt t ca cc sn phm gim phn cho php xc dnh

tn s ti t hp gia mt gene v tm ng ca n - y l cch lp bn
140
tm ng (map the centromere). K thut lp bn ny da trn mt c

im ca gim phn, l: cc tm ng tng ng ca cc nhim sc
th b m tch ra gim phn I, v cc tm ng ca cc chromatid ch
em tch nhau gim phn II. Nh vy, trong trng hp khng c trao
i cho gia mt gene v tm ng ca n, cc allele ca gene (v d A
v a) tch nhau gim phn I, s phn ly ny c gi l phn ly gim
phn I (first-division segregation). Thay v, nu nh mt trao i cho xy
ra gia gene v tm ng ca n, cc allele A v a ca n s khng c
phn ly cho n lc xy ra gim phn II; s phn ly ny c gi l phn
ly gim phn II (second-division segregation). Nh th, khi phn ly gim
phn I xy ra, ch c th c hai kiu trt t sp xp ca cc sn phm gim
phn, l AAaa v aaAA. Tuy nhin, c th c bn kiu ca phn ly
gim phn II, bi v s sp xp ngu nhin ca cc nhim sc th tng
ng k gia I v ca cc chromatid k gia II. Bn s sp xp ny
c hnh dung nh th ny: AaAa, aAaA, AaaA, v aAAa.
T l phn trm ca cc nang c kiu phn ly gim phn II ca mt
gene c th c s dng lp bn cho gene gn lin vi tm ng
ca n. Chng hn, ta gi s rng c 30% s nang t mt php lai c kiu
phn ly gim phn II i vi cc allele A v a. iu ny c ngha l 30%
s t bo tri qua gim phn c mt th trao i cho gia A v tm
ng ca n. Hn na, trong mi t bo xy ra mt trao i cho, hai
trong s cc chromatid l cc th ti t hp v hai ci cn li l nhng th
khng ti t hp. Ni cch khc, mt trao i cho n cho ra bn sn
phm gim phn, m mt na trong s l cc th ti t hp v mt na
l cc th khng ti t hp. Nh vy, tn s trao i cho bng 30% tng
ng vi tn s ti t hp l 15%. Theo quy c, khong cch bn phn
nh tn s ca cc sn phm gim phn c ti t hp hn l phn nh tn
s ca cc t bo m trong trao i cho xy ra. V vy, khong cch
bn gia mt gene v tm ng ca n c cho biu thc sau:
(S nang c cc kiu phn ly gim phn II)
Tng s cc nang
100
Cng thc ny c gi tr chng no gene nm gn tm ng sao cho

mt vi trao i cho phc c th xy ra. Nh th, cc tr s lin kt ng
tin cy c xc nh tt nht cho cc gene m chng nm kh gn tm
ng. V tr ca cc gene xa hn lc c thc hin bng cch lp
bn ca cc gene ny gn lin vi cc gene nm gn tm ng hn.
Ti t hp nguyn phn (mitotic recombination)
S trao i cho cng c th xy ra trong nguyn phn, mc d vi tn
141
s thp hn khong 1000 ln so vi gim phn. Bng chng u tin v ti

t hp nguyn phn (mitotic recombination) thu c rui gim, nhng
li c nghin cu k nht cc vi nm, c bit l nm men bia v
Aspergillus. V cc bn di truyn c th thit lp t cc tn s ti t
hp trong nguyn phn. Khong cch bn tng i gia cc gene c
th i khi tng xng vi khong cch bn da trn cc tn s ti t
hp trong gim phn, nhng cha r l do v sao cc khong cch ny li
thng khc nhau mt cch ng k. Nhng s tri ngc, khng nht
qun ny c th l kt qu hoc l ca cc c ch tip hp khc nhau hoc
l ca s phn b khng ngu nhin ca cc v tr trao i tim nng.
Khong cch bn v khong cch vt l
Nh cp trc y, khong cch bn gia cc gene c c
lng bng cc php lai di truyn ni chung l tng ng vi khong cch
vt l, hay di ca DNA, m n tch bch cc gene. Mt trng hp
ngoi l chnh l vng tm ng, khng c ti t hp nhng c th cha
mt di DNA kh ln. Hn na, r rng l ti t hp c th thng
c khu tr trong cc vng c bit, v khng phi hon ton ngu nhin
trn sut chiu di ca nhim sc th.
Bng cch so snh cc bn di truyn (genetic map) v bn vt l
(physical map), hnh 4.24 cho thy c khong cch bn c tnh c
(bng centiMorgan, vit tt l cM) ln s lng kilobase (1kbp = 1000 bp)
trong DNA (bn vt l). K bn bn di truyn ca mi nhim sc th
l bn vt l da trn cc nghin cu xc nh bng nhim sc th (hnh
4.24). Bn mi ny c tim nng ht sc to ln trong vic gip cc nh
khoa hc xc nh v tr cc gene gy ra cc bnh c th v sau kim tra
DNA xem iu g gy ra bnh tt .
Bn di truyn
Bn vt l
1. Bn di truyn
(2-5 cM)
3. Nhn din gene

(to dng cDNA v
xc nh trnh t)
2. Bn vt l (bn
Nhim sc th
(A)
Trnh t DNA STS 1000 kb). Cc th vin

YAC xp gi nhau.
(B)
4. Xc nh trnh t
(y B gene
Ngi vo 4/2003)
Hnh 4.24 Hai cch so snh khong cch bn (A v B); khong cch bn
d truyn c cho bng n v cM trn mt nhim sc th v khong
cch vt l c cho bng s kilobase trong trnh t DNA.
142
Gn y, mt n lc to ln c tp trung hng ti thu nhn cho

c mt bn di truyn ca b gen ngi (xem hnh 4.24, v cc trang
web http://www.genome.gov/ v http://www.ncbi.nlm.nih.gov/Omim/).
Bng cch s dng cc ch th phn t (molecular markers) khc nhau
(hin gi c bt c ti hng ngn marker tri khp b gene ngi) nh:
(i) cc a hnh di phn on DNA (restriction fragment length
polymorphism = RFLPs), ngha l cc bin i trong cc trnh t DNA ca
cc sinh vt thuc mt loi no m c th xc nh c bng s tch
on cc trnh t ny nh s dng cc enzyme gii hn (chng 10), v s
bin i nm bn trong v tr gii hn; v RFLPs c th c s dng
o a dng ca mt gene trong qun th; hay (ii) V tr trnh t ch
(sequence tagged site = STS), l mt trnh t c nht t mt v tr
nhim sc th bit m c th khuych i bng phng php PCR; cc
STS hot ng nh l nhng marker vt l cho vic lp bn b gene
(genome mapping) v to dng (cloning) v.v...
Lu : Vn lp bn bng phn tch b bn cc vi nm v vi
to tm dng ti y bi v n s c trnh by y trong gio trnh Di
truyn hc vi sinh vt v ng dng. Cc hin tng ti t hp bn trong
gene (recombination within genes) v php phn tch b tr (complementation) hay l trc nghim cis-trans (cis-trans test) s c cp trong
chng 6 v trnh by chi tit trong gio trnh va ni trn.
Cu hi v Bi tp
1. (a) Trnh by cc c ch xc nh gii tnh cc sinh vt, v nu
ngha thc tin ca chng.
(b) C s di truyn hc ca hin tng bt hot nhim sc th X l g?
(c) Phn bit cc tnh trng lin kt vi gii tnh, tnh trng b gii hn
bi gii tnh v tnh trng chu nh hng ca gii tnh, v cho cc v d.
2. (a) Ni dung c bn ca thuyt di truyn nhim sc th l g? Tn s
tn s ti t hp l g v c ng dng trong di truyn hc nh th no?
Cho v d.
(b) Hy chng minh: Tn s ti t hp (r) ca hai cp gene bt k trn
mt cp nhim sc th tng ng nm trong gii hn 0 r 0,5. C nhn
xt g v mi lin h gia cc quy lut di truyn lin kt v phn ly c
lp?
3. rui gim, ngi ta tin hnh mt s php lai v nhn c kt
qu di y. Hy gii thch c s di truyn cho mi tnh trng v xc
nh kiu gene ca cc c th.
143
P: Ci thn thm, mt trng c thn vng nht, mt

F1: Gii ci = tt c vng nht, mt
Gii c = tt c vng nht, mt trng
F2: 27 vng nht, mt : 25 vng nht, mt trng: 9 thm, mt : 8
thm, mt trng. (Bit rng khng c s khc nhau v t l phn b c ci mi kiu hnh ca F2).
4. Mt php lai gia rui gim ci cnh kha vi rui gim c cnh bnh
thng, i con gm c 35 con ci cnh kha, 38 con ci cnh bnh thng
v 33 con c bnh thng. (a) Hy xc nh phng thc di truyn ca
kiu hnh cnh c kha v s lai. (b) Trn thc t c xut hin rui gim
ci cnh kha thun chng hay khng? Ti sao?
5. Khi tin hnh lai gia mt rui gim ci mt v cnh ngn vi rui
gim c mt nu v cnh di thu c tt c i con c mt v cnh
di. Kt qu tp giao ca cc rui gim F1 thu c F2 nh sau:
Rui gim ci
Rui gim c
76 , di
24 , ngn
39 , di
37 nu, di
13 , ngn
11 nu, ngn
Hy xc nh quy lut di truyn ca cc tnh trng v lp cc s lai.

6. Mt ni rui gim kiu di c cho lai vi mt ni khc ng hp v
cc th t bin lin kt trn X l m, r v v. Sau em cc rui gim ci
F1 lai ngc vi cc con c thuc ni ln th nhn c s lng cc kiu
hnh i con ca chng nh di y.
Kiu hnh
S lng
Kiu hnh
S lng
+
m
+
+
331
2
73
14
m
m
+
m
10
81
0
309
+
+
r
+
+
+
+
v
r +
+v
r v
r v
Hy xc nh trt t cc gene v lp bn vi khong cch tng i

gia cc th t bin ny.
7. Xt cc php lai sau y rui gim v ba gene lin kt vi gii tnh:
P: + + +/+ + + y w m/Y
F1: Tt c u kiu di
144
Nu em cc rui gim ci F1 lai phn tch vi cc con c dng kim

tra tnh c tn s ca cc kiu hnh nh sau:
Cc lp kiu hnh
Tn s
Nhm b m (khng ti t hp)

Nhm ti t hp ca m vi y v w
Nhm ti t hp ca y vi w v m
Nhm ti t hp ca w vi y v m
0,664
0,329
0,0057
0,00086
a) Hy xc nh kiu gene ca cc rui gim F1.

b) Biu din v tr v khong cch tng i ca cc gene.
c) Tnh h s trng hp v nhiu.
d) Tnh s c th k vng cho mi kiu hnh i con (bit rng tng
s c th l 10.495).
8. Mt rui gim ci d hp v c ba gene +/sc; +/ec; +/vg c cho lai
vi mt con c ng hp ln v c ba gene ny. i con gm c:
sc ec vg
+ + +
sc ec +
+ + vg
233
239
241
231
sc + vg
+ ec +
sc + +
+ ec vg
12
14
14
16
Hy gii thch kt qu ny v ch ra bn lin kt ph hp.

9. Khi lai hai rui gim Drosophila u d hp v cc tnh trng ln lin
kt l mt nu v thn en cho kt qu nh sau: 52 thn vng nht, mt
: 9 thn vng nht, mt nu : 10 thn en, mt : 9 thn en, mt nu.
Hy gii thch kt qu v lp s lai.
10. rui gim, mt qu thn (k), mt dng mu (cd), v thn mun (e) l
ba allele ln lin kt vi nhau. Nu em cc rui ci mt thn, dng mu
ng hp lai vi cc rui c thn mun ng hp, thu c cc rui F1 tt
c u c kiu di. Nu em cc rui ci F1 d hp lai vi cc con c mt
thn, dng mu, thn mun thu c i con gm 1000 con, trong :
Mt thn, dng mu 440 Thn mun, mt mu 23
Thn mun
443 Mt thn
25
Mt thn, thn mun
32 Mt thn, mu, mun
1
Mt mu
34 Kiu di
2
a) Xc nh thnh phn gene trn mt nhim sc th ca rui ci F1.
b) V bn ca cc gene v tnh h s trng hp v nhiu.
145
Ti liu Tham kho

Ting Vit
Dubinin NP. 1981. Di truyn hc i cng (Bn dch ca Trn nh
Min v Phan C Nhn). NXB Nng Nghip, H Ni
Hutt FB. 1964. Di truyn hc ng vt. (Bn dch ca Phan C Nhn).
Phan C Nhn. 2001. Di truyn hc ng vt. NXB Khoa hc v K
thut, H Ni.
truyn hc (2 tp). NXB Gio Dc, H Ni.
Watson JD. 1968. Chui xon kp: Hi k v vic pht minh ra cu trc
ca DNA. (Bn dch ca L nh Lng v Thi Don Tnh). NXB Khoa
hc v K thut, H Ni, 1984.
Ting Anh
Ayala FJ, Kiger JA. 1980. Modern Genetics. Benjamin/Cummings
Brooker RJ. 1999. Genetics - Analysis and Principles. Benjamin/
Cummings Publishing Company, Inc., Menlo Park, CA.
Clegg CJ, Mackean DG. 2000. Advanced Biology : Principles and
Applications. 2nd ed., John Murray Published Ltd, London.
Kalthoff K. 1996. Analysis of Biological Development. McGraw-Hill,
Inc., New York.
Karpen GH. 1994. Position-effect variegation and the new biology of
heterochromatin. In: Current Opinion in Genetics & Developmment, Vol
4, No 2 (Stillman B and Green M, eds.), pp 281-291.
Kimball J. 2004. http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/
Martin E, Ruse M, Holmes E. 1996. Oxford Dictionary of Biology. 3rd.
ed., Oxford University Press, Oxford, UK.
McKusick V. 1998. Mendelian Inheritance in Man. 12th ed., Johns
Hopkins University Press, Baltimore.
146
Rastan S. 1994. X chromosome inactivation and the Xist gene. In: Current
Opinion in Genetics & Developmment, Vol 4, No2 (Stillman B and Green
M, eds.), pp 292-297.
Company, Inc., Menlo Park, CA.
Wellnitz WR. 1995. Genetics: Problem Solving Guide. 2nd ed., Wm.C.
Brown Publishers. Dubuque, Iowa.
Yablokov AV. 1986. Population Biology (Progress and problems of
studies on natural populations). MIR Publishers, Moscow. pp17-30.
Mt s trang web
National Human Genome Research Institute (NHGRI)/ National Institute
of Health (NIH). 2005: http://www.genome.gov/
http://www.ncbi.nlm.nih.gov/
147
Chng 5
Bn cht Ha hc v Ti bn
ca Vt cht Di truyn
Trc tin, chng ta cn nm cc c tnh thit yu ca vt cht di
truyn sau y: (1) c tnh thng tin sinh hc: cha ng thng tin cn
thit cho vic xc nh cu trc ca tt c cc protein c th ca loi (cc
gene cu trc) v iu khin cc hot ng sinh trng, phn chia v bit
ho t bo; (2) c tnh ti bn: kh nng t sao chp chnh xc, m bo
thng tin di truyn ca th h sau ging vi th h trc; (3) c tnh hot
ng ca cc gene: cc gene trong b gene c kh nng tng hp ra cc
sn phm l nhng phn t tham gia vo mi ng sng cn bn ca t
bo (phin m v dch m); (3) c tnh bin i: kh nng b bin i t
nhiu qu trnh khc nhau (nh t bin, ti t hp, cc yu t di truyn
vn ng). Chnh s bin i a dng ny to ra cc ngun bin d di
truyn a dng v phong ph cho s chn lc v tin ho.
Ngy nay chng ta u bit rng vt cht di truyn chnh l cc
nucleic acid m hu ht sinh vt l loi deoxyribonucleic acid (DNA) v
mt s virus l ribonucleic acid (RNA). Trong chng ny, chng ta s
tm hiu thnh phn ha hc v cu trc cng nh c ch ti bn ca vt
cht di truyn l cc i phn t DNA v RNA.
I. Bng chng vt cht di truyn l cc nucleic acid

1. Cc th nghim bin np vi khun
Nm 1928, Frederick Griffith t nn tng cho vic xc nh DNA l
vt cht di truyn thng qua th nghim bin np (transformation) trn ph
cu khun Streptococcus pneumoniae. Cc vi khun kiu di c v bc
bng polysaccharide mc thnh cc khun lc hay dng c trng bng
dng nhn (S: smooth); chng c coi l c (virulent) v c kh nng
gy vim phi lm chut cht. Mt ni t bin ca n mt kh nng hnh
thnh v bc v mc thnh cc khun lc b, x x (R: rough); chng l
cc vi khun khng c (avirulent).
Griffith tin hnh cc th nghim khc nhau v nhn thy rng: (1) Nu
tim cc vi khun sng ni S, chut cht; (2) Nu tim cc vi khun sng
ni R, chut sng; (3) Nu tim cc vi khun sng ni S b git cht
bng nhit, chut sng bnh thng; (4) Nhng khi tim hn hp gm cc
vi khun ni R cn sng v vi khun ni S b git cht bng nhit, kt
qu bt ng l chut cht. T mu mu ca cc con chut cht ny ng
phn lp c cc vi khun ni S cn sng. iu chng t rng bng
148
cch no cc mnh v t bo vi khhun ni S b git bi nhit xm

nhp vo t bo R sng v lm bin i n thnh vi khun S sng v gy
c. Qu trnh ny gi l bin np v cht trong mnh v t bo S gy
s bin np c th c gi l tc nhn bin np (transformating
agent). Vy bn cht ca tc nhn ny l g?
Ni S
sng
Ni R
sng
Ni S
cht
S cht + R
sng
Hnh 5.1 Th nghim ca Griffith (t tri sang l 1-4 nh m t trong bi).
Trong hn mi nm tri k t sau th nghim ca Griffith, Oswald

Avery cng vi MacLeod v McCarty tin hnh tr li th nghim bin
np ny nhng trong ng nghim (in vitro). H tinh chit cc thnh phn
ca tc nhn gy bin np v cho cc enzyme khc nhau tc ng thm d
ln hot tnh ca cht chit ny. Kt qu cho thy hot tnh ca cht chit
ch b phn hy bi deoxyribonuclease (DNase) - enzyme c kh nng
phn ct lm suy thoi ch i vi DNA, m khng b tc ng phn hy
ca ribonuclease (RNase) - enzyme lm suy thoi ch cc RNA, cng nh
ca cc protease (nh trypsin v chymotrypsin) - enzyme phn gii
protein. Vo nm 1944, nhm nghin cu ca Avery chng minh c
rng: DNA l vt cht mang thng tin di truyn, ch khng phi protein.
2. Tnh n nh ca hm lng DNA cc sinh vt bc cao
Trc khi Avery v cs cng b kt qu ny, a s cc nh ha sinh hc
vn tin rng gene chnh l protein. V vy sau kt qu hin nhin , nhiu
nh khoa hc vn cn nghi ng tnh ph qut ca n.
Vo lc ny, cc nghin cu bn cht ha hc ca nhim sc th
khng nh rng, hu ht DNA c khu tr trong cc nhim sc th
trong nhn. Hn na, cc phn tch ha hc ca A.E.Mirsky v H.Ris
149
(USA) v ca R.Vendrely (France) cho thy hm lng DNA mi b

nhim sc th lng bi lun lun n nh i vi mt c th nht nh v
bng hai ln hm lng DNA mi t bo tinh trng n bi. Chng hn,
cc s liu tng ng b l xp x 6,6 v 3,3 picogam (1pg =10-12g).
3. Cc th nghim virus
3.1. Th nghim Hershey-Chase
Nm 1952, Alfred D.Hershey v Martha Chase tin hnh cc nghin
cu nh du ng v phng x loi th thc khun (bacteriophage,
thng ni gn l phage) gi l T2 vn k sinh vi khun Escherichia
coli. Phage ny cha mt li DNA v lp v bo v bng protein. Da vo
c im nguyn t lu hunh (S: sulfur) ch c trong protein v nguyn
t phosphor (P) ch c trong nucleic acid, h nh du protein bng
cht ng v phng x S35 v DNA bng P32 bng cch cho cc phage ny
sinh trng trn cc mi trng c S35 v sinh sn khi c S32. Cc virus
nh du c s dng theo di thnh phn no t virus ban u i
vo t bo ch v sau xut hin trong cc phage th h con.
Ht
virus
DNA
V virus
Hnh 5.2 Th nghim Hershey-Chase. (a) Phage bm b mt ngoi mng t

bo vi khun; (b) bm li DNA vo trong v li lp v protein bm ngoi;
(c) ti bn, phin m v tng hp hng lot protein ca virus; (d) lp rp li +
v to ra cc virion; (e) enzym lysozyme ph hy vch t bo vi khun v
phng thch cc phage th h con.
Kt qu cho thy trong cc phage th h con ch c hu nh DNA

dng ban u v khng h c protein dng ny (hnh 5.2). Hn na, lp v
protein dng ban u bm bn ngoi mng t bo vi khun, khng thc
hin chc nng no sau khi DNA c tim vo trong vi khun. Nh
vy, vt cht di truyn ca phage T2 l DNA, ch khng phi protein.
3.2. Th nghim chng minh vt cht di truyn ca mt s virus l RNA
150
Sau ny, nm 1956 A.Gierer chng minh rng RNA c tinh sch t
virus m thuc l (tobacco mosaic virus = TMV) c kh nng ly nhim
khi khng c bt k protein no thuc virus. Kt qu phn tch cc virus
th h con cho thy chng hon ton ging vi cc virus sinh ra t s cho
ly nhim bng cc virus cn nguyn vn. Bng chng RNA l thnh phn
di truyn ca TMV cng c Fraenkel Conrat v B.Singer ti xc
nhn nm 1957 trong th nghim "lp rp cho" gia li RNA v v
protein ca hao kiu TMV l S v HR.
II. Thnh phn ha hc v cu trc ca DNA

Cc nucleic acid (DNA, RNA) l nhng polymer sinh hc, c trng
lng phn t ln, gm nhiu n phn (monomer) l cc nucleotide ni
vi nhau to thnh cc chui hay mch polynucleotide - cu trc s cp
ca cc phn t nucleic acid.
1. Cu trc ca cc nucleotide
lin kt glycosid
Hnh 5.3 Bn loi base ca DNA v cu trc mt nucleotide (dAMP).
Mi nucleotide gm ba thnh phn: mt nhm phosphate, mt gc

ng pentose v mt trong bn loi base nit (cc dn xut ca purine
hoc pyrimidine). V cu trc, nhm phosphate ni vi gc ng ti
nguyn t carbon s 5 (C5') bng mt lin kt ester v base nit ni vi
gc ng ti nguyn t carbon s 1 (C1') bng mt lin kt -glycosid
(Hnh 5.3). Lu : (1) Cc base l thnh phn c trng qui nh tn gi
cc nucleotide mang chng. Trong DNA cha bn loi base c bn:
151
adenine (A), thymine (T), guanine (G) v cytosine (C); trong RNA cng
cha bn loi nhng ch khc l thymine c thay bi uracil (U).
(2) ng pentose ca RNA l D-ribose v ca DNA l 2-deoxy-Dribose (k hiu D-: ch dng ng quay phi phn bit vi dng Lquay tri khng c trong thnh phn ca cc nucleic acid t nhin). Hai
gc ng ny khc nhau C2'; trong ribose l nhm -OH v trong
deoxyribose l -H. S c mt ca thnh phn ng trong cc nucleotide
phn bit hai loi ribonucleotide v deoxyribonucleotide cu to nn hai
loi nucleic acid tng ng l RNA v DNA.
(3) Cu trc "base + ng" gi l nucleoside; cch c v vit tt
tng ng vi cc base A, T, G v C trong DNA nh sau: deoxyadenosine
(dA), deoxythymidine (dT), deoxyguanosine (dG) v deoxycytidine (dC);
cch gi cho cc nucleoside trong RNA ch cn b tin ng "deoxy" (d),
v thay cho dT l uridine (U). V nu c y tn gi ca mt
nucleotide ch cn thm ci "ui" 5'-monophosphate, v d hnh 5.3.
(4) Tnh phn cc trong cu trc mt nucleotide cn th hin cc
nhm hydroxyl (-OH) hai v tr C5' (hnh thnh lin kt ester vi nhm
phosphate to ra nucleotide) v C3' (hnh thnh lin kt phosphodiester
vi nucleotide khc to chui polynucleotide).
2. Cu trc chui polynucleotide
u 5'
Lin kt 3',5'-phosphodiester v
chiu 5'3' ca chui polynucleotide
u 3'
Hnh 5.4 Cu trc chui polynucleotide ca DNA.
152
Cc nucleotide trong DNA hoc RNA ni vi nhau bng cc mi lin

kt 3',5'-phosphodiester gia gc ng ca nucleotide ny vi nhm
phosphate ca nucleotide k tip, to thnh chui polynucleotide (nh s
xc tc ca cc enzyme tng ng l DNA- hoc RNA-polymerase). V
vy cc chui ny bao gi cng c ko di theo chiu 5'3' (u 5'
mang nhm phosphate t do v u 3' cha nhm -OH t do) v c b
khung gm cc gc ng v phosphate lun phin nhau, cn cc base
nh vy c trnh t c c theo mt chiu xc nh (hnh 5.4).
Thng thng ngi ta biu din trnh t base 5'3' theo chiu t tri
sang phi. V d di y cho thy cc chui RNA v DNA ch khc nhau
bi base U v T v gc ng trong cc nucleotide ca chng.
chui RNA 5'- AUAGACUACG-3'
chui DNA 5'- dAdTdAdGdAdCdTdAdCdG-3'
3. Thnh phn ha hc v cu trc ca chui xon kp DNA
3.1. Thnh phn ha hc ca DNA
Nm 1949, E.Chargaff p dng phng php sc k giy vo phn tch
thnh phn ha hc ca DNA cc loi khc nhau (Bng 5.1; c th xem
trong Watson et al 1987, tr.73) khm ph ra ba im quan trng sau
y: (1) S lng bn loi base trong DNA l khng bng nhau; (2) T l
tng i ca cc base l khng ngu nhin; v trong tt c cc mu DNA
nghin cu tn ti mi tng quan v hm lng (%) gia cc base nh
sau: A T v G C, ngha l t s (A+G)/ T+C) 1; v (3) Mi loi c
mt t l (A+T)/(G+C) c th.
Bng 5.1 Thnh phn base ca DNA mt s loi (t nhiu tc gi)
Sinh vt
A%
T%
G% C%
Phage lambda
Phage T7
Mycobacterium tuberculosis
Escherichia coli
Aspergillus niger (nm mc)
Saccharomyces cerevisiae
Triticum (la m)
Zea mays (ng)
Salmo salar (c hi)
Gallus domestica (g nh)
Homo sapiens (ngi)
21,3
26,0
15,1
24,7
25,0
31,3
27,3
26,8
29,7
29,5
30,9
22,9
26,0
14,6
23,6
24,9
32,9
27,1
27,2
29,1
27,7
29,4
28,6
24,0
34,9
26,0
25,1
18,7
22,7
22,8
20,8
22,4
19,9
27,2
24,0
35,4
25,7
25,0
17,1
22,8
23,2
20,4
20,4
19,8
A+G
T +C
A+T
G+C
1,00
1,00
1,00
1,03
1,00
1,00
1,00
0,98
1,02
1,08
1,01
0,79
1,08
0,42
0,93
1,00
1,79
1,19
1,17
1,43
1,34
1,52
153
3.2. Cu trc chui xon kp

Vo nm 1951-52, vic nghin cu cu trc ba
chiu ca DNA bng phn tch nhiu x tia X c bt
u bi Maurice Wilkins v Rosalind Franklin. Cc
bc nh chp c 1952 (hnh 5.5) gi rng DNA
c cu trc xon gm hai hoc ba chui. Lc ny
Anh cn c mt s nghin cu khc nhm pht trin
l thuyt nhiu x ca Linus Pauling tm hiu cu
Hnh 5.5 nh chp DNA tinh th bng tia X ca Franklin.
trc DNA. Tuy nhin, gii php ng n nht l chui xon kp (double
helix) b sung do James Watson v Francis Crick a ra nm 1953. M
hnh ny (hnh 5.6) ph hp vi cc s liu ca Wilkins v Franklin cng
nh ca Chargaff. S kin ny m ra mt bc ngot mi cho cho s ra
i v pht trin vi tc nh v bo ca di truyn hc phn t v sinh
hc ni chung.
Lin kt
hydro
B khung ng-phosphate
Hnh 5.6 Cc m hnh cu trc DNA. Bn tri l m hnh khng gian lp y.

Hnh gia l chui xon dui thng cho thy cc cp base gia v hai b
khung ng-phosphate hai bn, vi cc thnh phn c ch ra bng cc mi
tn. Bn phi l s chui xon kp vi hai si i song song.
M hnh Watson-Crick hay DNA dng B c cc c im sau:
154
(1) DNA gm hai chui i song song (antiparallel) cng un quanh

mt trc trung tm theo chiu xon phi, vi ng knh 20Ao (1angstrom
= 10-10m), gm nhiu vng xon lp li mt cch u n v chiu cao
mi vng xon l 34 Ao, ng vi 10 cp base (base pair, vit tt l bp).
(2) Cc b khung ng-phosphate phn b mt ngoi chui xon v
cc base nm bn trong; chng xp trn nhng mt phng song song vi
nhau v thng gc vi trc phn t, vi khong cch trung bnh 3,4 Ao.
(3) Hai si n gn b vi nhau bng cc mi lin kt hydro (vn l
lc ha hc yu) c hnh thnh gia cc cp base i din theo nguyn
tc b sung "mt purine - mt pyrimidine". C th l, trong DNA ch tn
ti hai kiu kt cp base c th l A-T (vi hai lin kt hydro) v G-C
(vi ba lin kt hydro) (xem cc hnh 5.6 v 5.7).
(4) Tnh cht b sung theo cp base dn n s b sung v trnh t cc
base gia hai si n ca mi chui xon kp. V vy, trong DNA si kp
bao gi cng c: A = T v G = C (quy lut Chargaff); ngha l (A+G) =
A+T
A+G
c th cho tng loi.
(T+C) hay t s
= 1 , cn t l
T +C
G+C
Hnh 5.7 Hai kiu kt cp base ca DNA. Cp G-C ni vi nhau bng ba lin
kt hydro (biu th bng cc ng chm), c cng hnh dng chnh xc nh cp
A-T ni vi nhau bng hai lin kt hydro. Cc mi tn ch v tr lin kt gia base
vi gc ng.
Cn lu rng, hai c im quan trng nht trong cu trc DNA l s

phn cc ngc chiu ca hai si n (5'3' v 3'5') v nguyn tc b
sung gia cc cp base. Hai c im ny cho php gii thch mt cch c
155
bn cc c ch di truyn cp phn t (ti bn, phin m v dch m).

4. S lc v cc c tnh ha l ca cc nucleic acid
4.1. Cc dng ca DNA
M hnh Watson-Crick hay DNA dng B l cu trc ph bin. Tuy
nhin, sau ny ngi ta cn pht hin ra nhiu dng xon phi khc
(A,C,D...); chng c mt s bin i so vi DNA-B (xem bng 5.2).
Bn cnh cc dng DNA xon phi, t
nm 1979 Alexander Rich v ng s cn
pht hin thm mt dng DNA xon tri duy
nht cho n nay, gi l DNA-Z. Dng DNA
ny c cc b khung zigzag un gp khc
theo chiu tri, mi vng xon di 45,6Ao
cha 12 cp base (hnh 5.8 v bng 5.2).
DNA dng Z cha cc si gm cc purine
v pyrimidine xp xen k nhau, th d:
--GCGCGCGC---CGCGCGCG-Mc d Rich khm ph DNA-Z khi nghin
cu v cc hp cht m hnh, song cu trc
ny dng nh cng c mt trong cc t bo
sng mt t l nh v vn cn cha tht s
hiu r chc nng ca n.
Hnh 5.8 DNA-B v DNA-Z
Bng 5.2 c im ca cc dng DNA - A, B, C v Z
Dng
Chiu xon S bp/vng xon
ng knh chui xon
A
Phi
11,0
23Ao
B
Phi
10,0
19Ao
C
Phi
9,3
19Ao
Z
Tri
12,0
18Ao
*Ngun: J.Kimball (t internet). V chi tit, xem trong Watson et al 1987, tr.249.
4.2. Bin tnh v hi tnh ca DNA

4.2.1. Khi nim bin tnh v hi tnh
Mt trong nhng c im quan trng nht ca DNA l hai mch n
b sung ca n gn vi nhau bng cc mi lin kt hydro, vn l lc lin
kt ha hc yu nn chng c th b phn hy di tc dng ca cc
enzyme, nng lng... lm cho hai mch n ca chui xon kp tch ri
nhau. Nh DNA mi c th ti bn, cc gene mi c th biu hin ra
156
cc sn phm ca mnh. Mt khc, DNA c th phc hi tr li trng thi

ban u theo mt qu trnh ngc li, ngha l c tnh thun-nghch.
Bng thc nghim, ngi ta chng minh iu bng cch s dng
cc tc nhn vt l v ha hc khc nhau. Chng hn, khi un nng t t
cc phn t DNA ln ti nhit gn 100oC (thng l 90-95oC), th cc
lin kt hydro ca chng b ph hy hon ton v hai si b sung tch ra.
Hin tng ny c gi l bin tnh (denaturation). Ngc li, khi lm
ngui t t dung dch t nng cha DNA b bin tnh han ton, cc si
n thng cp i vi si b sung ca chng v lm phc hi chui xon
kp nh lc u. Hin tng gi l hi tnh (renaturation).
V ng DNA giu A-T

- c t ch thnh
mt bp d ng s i n
Tm ph thuc vo hm l- ng G-C ca DNA

% hyperchromicity
DNA si kp giu GC
ch- a bnng chy
DNA E. coli
v i 50% G-C, c
Tm bng 69 o C.
50
60
C c v ng giu A-T t ch tr- c, c c v ng giu G-C t ch sau
70
80
Nhit oC
Hm l- ng G-C c th- c x c nh t Tm ca DNA
Hnh 5.9 DNA bin tnh tng phn. Hnh 5.10 S ph thuc ca Tm vo
hm lng GC ca 3 DNA khc nhau
nhit va phi hoc khi c mt cc tc nhn gy mt n nh nh

alkali hay formamide, th cc phn t DNA b bin tnh tng phn. Khi
ti cc vng giu cp AT s tch tng phn trc, trong khi cc vng giu
cp GC vn gi nguyn c tnh xon kp. iu ny c th l gii l do
mi cp AT ch c hai lin kt hydro r rng l km bn hn so vi mi
cp GC c ti ba mi lin kt nh th.
Nhit m ti cc si DNA b bin tnh hay tch nhau mt na
c gi l nhit nng chy (melting temperature), hay Tm. Tm l im
gia ca pha phuyn tip (hnh 5.9) v n ty thuc vo hm lng G-C
ca DNA, ngha l c trng cho DNA mi loi. V d, DNA ca E. coli
vi 50% G-C th c Tm l 69oC (hnh 5.10).
Ni chung, hm lng GC ca mt DNA c th bin thin t 22%
nm mc nhy Dictyostelium n 73% Mycobacterium phlei. iu ny
c th gy mt hiu qu mnh ln cc c tnh ha l ca DNA, c bit l
ln nhit nng chy, vn n tng tuyn tnh vi hm lng GC. Nhit
nng chy (Tm) ca mt DNA l nhit m ti hai si b bin tnh
hay tch nhau mt na. Ngoi ra, nng ion thp v cc dung mi hu
c cng thc y s bin tnh ca DNA.
157
4.2.2. ng dng trong lai phn t (hnh 5.11)

Ngi ta li dng kh nng ni trn ca DNA to ra cc phn t
DNA lai nhn to bng cch lm lnh t t hn hp cc DNA bin tnh t
hai loi khc nhau. K thut lai phn t (molecular hybridization) ny
c ng dng rng ri xc nh mc tng ng DNA ca cc
nhm phn loi khc nhau. V d, cc thc nghim cho thy c khong
25% tng s DNA ngi v chut c th lai vi nhau (Watson et al 1987).
Hnh 5.11 Bin tnh v hi tnh ca DNA (tri) v lai nucleic acid (phi).
Theo ngha rng, lai phn t hay lai nucleic acid c hiu l s tng
tc gia cc si nucleic acid b sung. N c th xy ra gia hai si DNA
hay gia cc si DNA v RNA, v chnh l c s ca nhiu k thut,
chng hn nh: lai mt mu d c nh du ng v phng x (radioactive
probe) lc ra DNA hay RNA bm vo mang lai l mt trong nhng th
nghim cho nhiu thng tin b ch nht c tin hnh trong di truyn hc
phn t. Hai kiu c bn ca lai phn t l phng php thm Southern
(Southern blots) v phng php thm Northern (Northern blots). Trong
, kiu u l lai bng mt mu d lc DNA, cn kiu sau dng lc
RNA. Mu d (probe) l cc cng c s cp c dng xc nh cc
trnh t b sung cn quan tm; n l mt nucleic acid si n c nh
du phng x v c dng xc nh mt trnh t nucleic acid b sung
bm trn mng lc nitrocellulose hay mng lai bng nylon. Ni chung,
mu d l mt dng (clone) c to ra bng cch xen DNA vo mt
vector. Thng thng hu ht cc vt d ny l cc dng thuc plasmid.
III. Kch thc b gene v tnh phc tp v mt tin ha

1. S lc v b gene ca cc virus, prokaryote v eukaryote
Virus l nhm "sinh vt" b nht cha c cu to t bo, khng tn ti
n c m k sinh bt buc cc t bo sinh vt tin nhn (prokaryote)
hoc sinh vt nhn chun (eukaryote); ch trong iu kin chng mi
c kh nng ti bn. Cc virus k sinh hoc gy nhim vi khun gi l th
158
thc khun (bacteriophage) hay phage. Cu trc ca cc virus tng i

n gin, gm hai phn chnh l li axit nucleic v v protein (hnh 5.12).
Mt s virus thc vt hoc cc virus gy ung th, AIDS, SARS ngi
v ng vt c b gene l RNA. S cn li bao gm nhiu virus k sinh vi
khun v ng vt c b gene l DNA si kp hoc si n, c mch thng
hoc mch vng (bng 5.3).
Cc enzyme
RNA
V (capsid)
Bao virus
Protein virus
Hnh 5.12 nh chp phage T4 (tri) v s cu trc ca HIV (phi).
Hnh 5.13 nh chp cc t bo E. coli (tri) v vt cht di truyn ca n

(phi), v bn di l nh hin vi in t ca plasmid pSC101.
Nhm prokaryote bao gm cc vi khun (bacteria) v vi khun c

(archae) l cc sinh vt c cu to t bo n gin nht. Vi khun
Escherichia coli (hnh 5.13) l i tng c s dng rng ri trong cc
nghin cu di truyn phn t. B gene chnh ca n l mt phn t DNA
si kp vng c kch thc ln (4.639.221 bp, vi 4290 gene m ha
protein v 53 gene RNA) gi l nhim sc th chnh. N thng tp trung
mt "vng nhn" (nucleoid), khng c mng nhn bao bc, v trng
thi siu xon (supercoiled DNA) di s kim sot ca cc enzyme
159
topoisomerase. Ngoi ra cn c nhiu phn t DNA si kp trn mch

vng khc c knh thc b hn nhiu, gi l cc plasmid (Vn ny
c trnh by k trong gio trnh Di truyn hc Vi sinh vt v ng dng).
Nhm eukaryote l nhm ln nht v tin ha a dng nht v trnh d
t chc c th, bao gm tt c cc sinh vt c cu to t bo (tr vi khun
v vi khun lam), c th l n bo hoc a bo. Trong t bo cha hai h
thng di truyn, b gene nhn ( trnh by chng 3 v 4) v b gene t
bo cht (xem chng 9). Kch thc b gene ca mt s sinh vt thng
gp c gii thiu cc bng 5.3 v 5.4.
2. Mi quan h gia kch thc b gene v tnh phc tp v tin ha
Da trn cc kt qu phn tch b gene ca cc virus v vi khun cng
nh ca b gene eukaryote (b nhim sc th n bi), cho php khi
qut nh sau: Kch thc ca b gene tng ln tng i cng vi mc
phc tp v tin ha. Tht vy, t bng 5.3 ta thy rng kch thc b
gene ca cc virus ni chung l rt nh so vi nhm prokaryote; v kch
thc b gene ca cc prokaryote li t ra qu n gin so vi ngay c
mt eukaryote n bo nh nm men.
V d: Trong khi DNA ca mt vi khun in hnh nh E. coli hn 4,6
triu cp base v cha 4.377 gene m ha protein (khng k 53 gene
RNA); th phage MS2 l mt trong cc virus b nht, b gene RNA ca n
cng ch c 3.569 base vi tt c 4 gene; hoc c kch thc ln nh virus
Epstein-Barr - b gene DNA si kp mch vng - cng ch c 172.282 cp
base vi tt c 80 gene. Nu xt trn c hai nhm prokaryote v eukaryote,
ta thy rng kch thc cc b gene bin thin rt rng: b gene i vi
mt sinh vt sng t do (mt vi khun) c bit l b nht cha khong
600.000 cp base DNA, trong khi cc b gen ngi v chut l khong 3
t. Nu xt ring nhm eukaryote, ta bit mi loi c mt s lng
nhim sc th c trng v n khng phn nh trnh tin ha ca cc
loi. Tuy nhin, v mt no r rng l c s tng quan thun gia hm
lng DNA ca cc b gene n bi v nc thang tin ha ca cc ngthc vt. D vy vn c mt s ngoi l so vi quy tc ny!
3. Hm lng DNA v nghch l gi tr C
Chng hn, mc d Psilotum nudum, i khi gi l "dng x lng", l
mt thc vt n gin hn nhiu so vi loi Arabidopsis thaliana vn l
mt thc vt c hoa thuc h ci, nhng n li c hm lng DNA ln
hn ti 3.000 ln. Mc d ta hiu ti sao, nhng c iu th v l trn 80%
b gene ca n l DNA lp li khng cha thng tin di truyn no c! Hay
mt s thc vt (nh ng, loa kn) hay mt s ng vt (nh lng th,
c) li c kch thc b gene ln gp nhiu ln so vi lp th (bng 5.3).
160
Mt s lng th cha DNA nhiu gp b gene chng ta n 30 ln,

nhng chc chn khng phi l chng phc tp gp chng ta 30 ln.
Bng 5.3 Kch thc b gene (genome) mt s sinh vt thng gp
B gene sinh vt
Virus
Phage -X174 ( E. coli)
Phage lambda ( E. coli)
Phage T2 hoc T4 ( E. coli)
Phage MS2 ( E. coli)
SV40 (gy khi u kh)
Virus SARS (v d, H5N1)
Epstein-Barr virus (EBV)
Prokaryote
Haemophilus influenzae
Chlamydia trachomatis
Streptococcus pneumoniae
Vibrio cholerae
Mycobacterium tuberculosis
Bacillus subtilis
Escherichia coli*
Agrobacterium tumefaciens**
E. coli O157:H7
Eukaryote
Saccharomyces cerevisiae
Schizosaccharomyces pombe
Plasmodium falciparum***
Neurospora crassa
Caenorhabditis elegans****
Arabidopsis thaliana
Drosophila melanogaster
Ngi (Homo sapiens)*****
La (Oryza sativa )
Loa kn (Lilium longiflorum)
Chut
Lng th
S bp
5.386
48.502
~2 105
3.569
5.226
29.600
172.282
1.830.138
1.042.519
2.160.837
4.033.460
4.411.532
4.214.814
4.639.221
4.674.062
5,44 106
S gene
Ghi ch
10 DNA si n vng
~61 DNA si kp thng
150-200 DNA si kp thng
4 RNA
DNA si kp vng
RNA
80 DNA si kp thng
1.738
936
2.236
3.890
3.959
4.779
4.377
5.419
5.416
5.770
12.495.682
12.462.637
4.929
22.853.764
5.268
38.639.769
10.082
100.258.171 ~19.000
25.498
115.409.949
122.653.977
13.379
~3,2 109 ~25.000
4,3 108 ~60.000
3 1011
?
2,2 109
?
?
109 - 1011
Gy nhim tai gia

Bnh ly qua tnh dc
Pneumococcus
2 NST; gy cholera
Gy bnh lao
C 4290 cistron
Vector hu ch...
Gy bnh ngi
Men bia ny chi
Nm men phn ct
Gy st rt nguy hi
+ 498 gene RNA
Gii tr.t u tin...
Thc vt c hoa
Rui gim
Gii tr.t 4/2003 ...
Ch thch: *C 4290 gene m ha protein, cn li l cc gene RNA; ** Vector

hu ch chuyn gene thc vt; *** Cng vi 53 gene RNA; **** Eukaryote
a bo u tin c xc nh trnh t; ***** c xc nh y trnh t vo
4/2003 bi HGP, vi tng cng 3.164.700.000 cp base; v theo c tnh mi
nht cng b ngy 21/10/2004 trn tp ch Nature, b gene ngi chng ta cha
khong 20.000-25.000 gene m ha protein, chim khong 2% ton b b gene.
161
Ngi ta gi tng hm lng DNA trong b gene n bi l gi tr C

(C-value). Vi phn tch trn cho thy khng h tn ti mt mi quan h
nht qun gia gi tr C v tnh phc tp ca mt sinh vt (nh lng th
vi th); ci c gi l nghch l gi tr C (C-value paradox).
4. V kch thc DNA cc bo quan
Kch thc DNA ca mt s bo quan (bng 5.4) cho thy chng c v
n gin v khng c du hiu tin ha r rt. Ni chung, kch thc mi
phn t DNA ty th (mitochondrial DNA = mtDNA) ca ngi v cc
ng vt c v thng nm trong khong 15.000-17.000 bp; v d mtDNA
ngi l 16.569 bp. Trong khi , kch thc mt DNA lp th
(chloroplast DNA = ctDNA hay cpDNA) phn ln t bo cc thc vt
thng vo khang 130.000 -150.000 bp. Chng hn, ctDNA la trng
(O. sativa) thuc hai nhm indica v japonica c kch thc tng ng l
134.494 bp v 135.525 bp, la m (Triticum aestivum) l 134.545 bp v
ng (Zea mays) l 140.384 bp...Cn cc plasmid hin din mt s t
bo thc vt thng c kch thc rt b khong 1-2 ngn cp base.
Bng 5.4 Kch thc DNA bo quan mt s sinh vt
DNA ty th
Ngi
D. melanogaster
S. cerevisiae
Plasmid
La (indica; japonica)
Ng
S cp base
16.569
19.517
85.779
1485 ; 2.135
1.913
DNA lp th
La (ind; jap)
Ng
Ma
Plasmid
N. crassa
Brassica
S cp base
134494 ; 134525
140.384
141.182
3581; 3675;7050
11.640
IV. T chc phn t ca cc nhim sc th

1. Cu trc cht nhim sc
y ta ch tm hiu t chc ca
DNA trong cc nhim sc th
eukaryote. Mi nhim sc th
eukaryote l mt phc hp
nucleoprotein bao gm mt phn t
DNA si kp mch thng kt hp
vi cc phn t protein c s gi l
histone (giu cc amino acid lysine
v arginine). Phc hp nh th gi l
cht nhim sc (chromatin).
Hnh 5.14 S cu trc mt nucleosome
162
n v t chc ca c s cc nhim sc th eukaryote l cc

nucleosome (hnh 5.14). Mi nucleosome c ng knh khong 11 nm,
gm mt khi cu tm phn t histone, (H2A+ H2B +H3+H4)2, gi l li
octamer v on DNA c kch thc 146 cp base qun 1 vng xung
quanh n (thng c m t n gin: mt on DNA di 160-200 bp
qun hai vng quanh octamer). Mt phn t H1 bm vo on DNA "ni"
(linker DNA) bn ngoi khi cu, gi vng s tng tc ca DNA vi cc
histone li. on DNA ni gia hai nucleosome di khong150 bp.
DNA cun cht
trong NST k gia
on DNA
si kp
NST k gia
Chui
nucleosome
Chromatin
c c
Si chromatin
30 nm
Cc nucleosome
Chui xon kp
DNA
Vng cun
vng
Vng xon
cht
NST
k gia
Hnh 5.15 T chc DNA trong nhim sc th eukaryote. DNA cun cht
trong nhim sc th k gia c m xon dn qua cc mc khc nhau (hnh
tri). DNA ng xon dn qua cc mc cho n khi hnh thnh nhim sc th k
gia nguyn phn, vi chiu di rt ngn khong 50.000 ln (hnh phi).
Nh vy, bc cu trc u tin ca chromatin c hnh dung di dng

mt chui cc nucleosome, hay si nucleosome (nucleosome fiber) c
dy 11 nm (1 nanomet = 10 Ao). Bc th hai ca ca s cun gp
chromatin c lin quan ti s xon li ca si nucleosome thnh ra mt
163
si dy 25 nm gi l mt solenoid. Cc histone H1 c coi l tham gia

vo s xon li ny bng cch tng tc vi cc phn t H1 khc. Bc th
ba ca s ha xon c l l cun vng ca si 25 nm thnh mt cu trc
kiu nh bn chi (brushlike) vi cc vng c neo dnh vo mt gi
trung tm (dy ~300 nm). y chnh l vng tho gin xon ca nhim sc
th, tng ng vi cht ng nhim sc (euchromatin). Sau cc dy
vng c sp xp trong cc khng gian ba chiu ny xon cht to thnh
cc vng gi l cht d nhim sc (heterochromatin) trn mt chromatid
vi dy khong 700 nm. Ti k gia ca nguyn phn, mi nhim sc
th c cu trc in hnh gm hai chromatid ch em (two sister
chromatids) dnh chung nhau tm ng (centromere) vi dy ton b
chng 1400 nm (hnh 5.15). Nh vy, cht nhim sc trong cc t bo
eukaryote tn ti hai dng: (1) Cht d nhim sc l cc phn cun xon
cht v khng c hot tnh phin m; v (2) Cht ng nhim sc l cc
vng gin xon v ch t cng c tim nng hot tnh.
2. S lc cc thnh phn DNA trong b gene eukaryote
Ni chung, trong mi b gene eukaryote bao gm cc kiu DNA chnh
sau y, v cho tin ta ly b gene ngi lm th d :
- DNA bn sao n (single-copy or unique), ngha l cc gene c mt
ch mt ln trong b gene; loi ny chim khong 75% b gene v bao
gm hu ht cc gene.
- DNA lp li (repetitive) bao gm mt s gene c lp li vi ln
cho n hng ngn ln trong b gene. Nhm ny c chia lm hai loi:
+ DNA lp li kiu phn tn (interspersed): loi ny chim khong
15% v phn b ri rc khp b gen gia cc gene cng nh bn trong cc
gene; bao gm cc trnh t Alu (l cc on DNA di khong 300 bp v
c lp li khong 300.000 ln trong b gene; chng c th c mt ch
tip gip hoc bn trong cc gene trong cc intron hoc cc vng khng
c dch m) v c cc on lp ni tip c s lng bin thn (VNTRs
= variable numbers of tandem repeats), vn l cc on lp ngn ch vi
cp base nhng c chiu di sai khc, hay cc tiu v tinh (mini- hay
microsatellite). V d: cc on lp phn tn (5'3') trong cc on Alu:
GCTGCGG........GCTGAGG........GCTGAGG
+ DNA v tinh (satallite) hay DNA lp li kiu ni tip (tandem):
loi ny chim khong 10% v c lp li rt nhiu ln, bao gm cc
trnh t n gin thng khu tr cc tm ng (centromere) v cc u
mt (telomere) ca cc nhim sc th. V d: cc on lp ni tip (5'3')
thuc cc microsatellite hay telomere:
164
5'-...TTAGGGTTAGGGTTAGGGTTAGGG...-3'
Nhn chung, b gene ngi c cc c im sau: (1) V b gene nhn,
kch thc b gene n bi l ~3,2 t bp; hu nh tt c mc phc tp
ca n u nm trong lp DNA bn sao n (~75%). B gene ngi c
coi l c cha khong 25.000 gene m ha protein. Trong a phn l
cc gene phn on vi cu trc phc tp (xem chng 6). Cc gene u
cha t 1 cho n trn 75 exon (on m ha protein) v c chiu di bin
thin t di 100 cho n khong 2.400.000 bp (gene gy ri lon dng
c DMD c xem l di nht vi 2,4 triu bp ny chim ~ 1,5% nhim
sc th X m n nh khu). Trnh t Alu c mt khp b gene. (2) V b
gene ty th, y l b gene mch vng vi 16.569 bp v cha ~ 40 gene.
V. Ti bn DNA
Sau khi khm ph ra cu trc DNA, Watson v Crick xut ba
kiu truyn thng tin di truyn c th c trong cc t bo: (1) Ti bn
(replication): DNADNA; (2) Phin m (transcription): DNARNA; v
(3) Dch m (translation): RNAProtein. Cc knh truyn thng tin di
truyn ny c gi l Gio l Trung tm (Central Dogma) ca sinh hc
phn t. Sau ny n nm 1970, Baltimore v Temin qua nghin cu c
ch hot ng ca b gene RNA virus Sarcoma b sung thm knh
RNADNA, gi l phin m ngc (reverse transciption) v n ngc
hng vi knh phin m ph bin. iu ny c minh ha hnh 5.16.
Dch m
Phin m
Ti bn
Phin m
ngc
Hnh 5.16 Cc kiu truyn thng tin di truyn (tri), v m hnh ti bn

DNA theo kiu bn bo ton do Watson v Crick xut.
1. Cc nguyn tc v c im chung ca ti bn DNA

Ti bn (replication) l mt c tnh quan trng nht ca vt cht di
truyn, nh s sng c duy tr lin tc, cc loi bo tn c tnh
cht c trng ca mnh, v con ci thng ging b m. Vy DNA v cc
b gene ni chung c ti bn nh th no?
165
Trong khi khm ph ra m hnh cu trc DNA, chnh Watson v Crick

a ra d on chnh xc (da trn nguyn tc b sung ca cc cp
base) rng s ti bn DNA phi din ra theo kiu bn bo ton (semiconservative) nh hnh 5.16. n 1956, S. Luria v Max Delbruck
ngh ba kiu ti bn c th c: bn bo ton, bo ton (conservative) v
phn tn (dispersive). Tuy nhin, nhiu th nghim sau nhanh chng
khng nh s ti bn DNA din ra theo kiu bn bo ton.
in hnh l th nghim ca Meselson v Stahl nm 1958 trn i
tng l E. coli bng phng php nh du ng v phng x N15 (nit
nng) kt hp vi ly tm siu tc (ultra-centrifugation). u tin cho vi
khun ny sinh trng trn mi trng N15; ri a tr li mi trng N14
(nit nh) v sau mt, hai hoc ba th h u c ly cc mu DNA.
tch DNA nng v nh, ngi ta cho trn ln cc mu ny vi cesium
chloride (CsCl) trc khi em ly tm. Khi ly tm, DNA c cc t trng
nng (heavy), nh (light) v trung bnh (intermediate) s tch thnh cc
vch tng ng khc nhau trong ng nghim (hnh 5.17).
DNA
cha m
Hnh 5.17 Th nghim Meselson-Stahl v s ti bn bn bo ton ca DNA.
Cc kt qu cho thy rng sau mt th h, 100% DNA si kp c t

trng trung bnh, ngha l mt si nng (t dng cha m) v mt si nh
(c tng hp mi). Kt qu ny cho php d an v kt lun s ti bn
xy ra theo kiu bn bo ton ng nh d on ca Watson v Crick
rng, cc si DNA lm khun cho s ti bn ca ring chng.
Di y l cc nguyn tc v c im chung ca ti bn DNA.
(i) Ti bn theo kiu bn bo ton v gin on (discontinuous);
(ii) S ti bn c bt u ti mt hoc nhiu v tr c th trn phn
t DNA v din ra ng thi theo hai hng ngc nhau gi l khi im
ti bn hai hng (bidirectional origin of replication). Ngha l, t khi
im ny DNA si kp m xon thnh hnh vng m sinh trng theo hai
hng i lp nhau to ra hai chc ti bn (replication fork). Mi khi
im ti bn cng vi hai chc nh vy goi l mt n v ti bn
166
(replicating unit hay replicon) c minh ho hnh 5.18. Ni chung, i

vi cc DNA mch vng (b gene mt s virus, vi khun, cc plasmid v
cc DNA bo quan ca eukaryote), mi phn t ch c mt khi im ti
bn; trong khi mi DNA trong nhim sc th eukaryote c nhiu khi
im ti bn hot ng theo mt trnh t c th (xem hnh 5.20).
khi im (Ori)
chc
sinh
trng
chc
sinh
trng
Hnh 5.18 Mt khi im v hai chc ti bn sinh trng theo hai hng
i lp nhau. y cng cho thy on mi RNA c tng hp trc.
(iii) Qu trnh ti bn DNA ph thuc vo mt h thng gm nhiu

protein v enzyme khc nhau (xem mc 2 bn di);
(iv) Ti mi chc ti bn, trc tin xy ra s tng hp cc on mi
RNA (primer) bi v cc DNA polymerase t n khng th bt u tng
hp mi c. Mt khc, do hai si n ca mi chc phn cc ngc
chiu nhau trong khi cc enzyme DNA polymerase v RNA polymerase
ch xc tc theo chiu 3' 5', cho nn phng thc ti bn DNA din ra
trn hai si khun l khng ging nhau: mt si lin tc hay cn gi l si
dn u (leading strand) v mt si khng lin tc hay cn gi l si ra
chm (lagging strand). Kiu ti bn nh th gi l ti bn na gin on
(semi-discontinuous).
S tng hp DNA khng lin tc di dng cc on ngn do R.
Okazaki pht hin u tin nm 1969; sau ny chng c gi l cc on
Okazaki (Okazaki fragments). Sau , cc on mi s c ct b v ch
trng c thay bng DNA, v cc on Okazaki c ni li bi enzyme
DNA ligase.
167
2. Cc enzyme tham gia ti bn DNA

Mc d mi nhm sinh vt c mt h thng cc enzyme v protein ti
bn ring, song chng c cc enzyme vi vai tr chung nht sau y:
(1) Protein nhn bit v bm vo khi im t hnh thnh nn
"phc hp m" (open complex). E. coli, l protein dnaA.
(2) DNA gyrase: m cun DNA siu xon pha trc mi chc ti bn.
(3) Helicase: tho xon DNA si kp ti mi chc to thnh cc vng
si n. E. coli, n cng gi l protein dnaB hay protein rep.
(4) Protein SSB (single strand binding protein): bm vo cc vng
DNA si n do helicase tch ra, gi cho tm thi khng dnh tr li v
nh mi si n mi c th lm khun (template) cho ti bn.
(5) Primase: tng hp RNA mi. E.coli, n cn gi l protein dnaG.
(6) Cc DNA polymerase xc tc chnh cho vic tng hp DNA mi
nh c hot tnh xc tc: polymerase 5'3', mt s cn c hot tnh c
sa: exonuclease 3'5'. E. coli, l DNA polymerase III.
(7) DNA polymerase va ct b dn on mi i trc nh hot tnh
ct b exonuclease 5'3', va ko di on Okazaki theo sau lp ch
trng. E. coli, l DNA polymerase I.
(8) DNA ligase: hn lin khe h gia cc on DNA mi bng cch
hnh thnh lin kt 3',5'-phosphodiester.
Bng 5.5 c tnh ca cc DNA polymerase E. coli v ngi
DNA polymerase E. coli
pol I
pol II
pol III
Polymerase 5'3'
Exonuclease 3'5'
Exonuclease 5'3'
DNA polymerase ngi
c
c
c
c
c
khng
c
c
khng
nh v
Ti bn
Sa cha
Chc nng
Polymerase 5'3'
Exonuclease 3'5'
Exonuclease 5'3'
Primase
Kt hp vi PCNA*
Mu trt (Processivity)
Tng hp si
nhn
c
khng
nhn
khng
c
ty th
c
khng
nhn
c
c
nhn
c
c
c
khng
khng
c
khng
thp
c
khng
khng
khng
khng
c
c
khng
khng
khng
c
c
khng
khng
c
cao
c
c
khng
khng
c
ra chm
sacha
c hai
dn u
ra chm
168
Lu : (i) E. coli, c ba loi protein dnaB, dnaC v dnaG hp thnh

mt phc hp c tn l primasome; trong protein dnaC bm protein
dnaB. Bng 5.5 m t cc c tnh ca cc DNA polymerase E. coli v
ngi i din cho cc nhm tng ng, prokaryote v eukaryote.
(ii) Tt c cc DNA polymerase u cn c mi vi mt nhm 3'-OH
t do; xc tc tng hp chui theo mt hng 5'3'; v ch mt s
enzyme ny c hot tnh c sa (proofreading activity) 3'5'.
(iii) Ngc vi E. coli, cc t bo ngi c t nht nm loi DNA
polymerase, trong ba loi chu trch nhim ti bn DNA nhn l cc
DNA polymerase alpha, delta v epsilon. Polymerase chu trch nhim
chnh cho tng hp trn si dn u (leading strand) v thm ch c si ra
chm (lagging strand). Polymerase kt hp vi mt RNA primase v
c coi l c cc hot tnh cho tng hp mt on mi RNA-DNA ngn.
C iu khng chc chn lm khi ni v chc nng ca alpha trn si ra
chm. V dng nh n thiu mt hot tnh c sa, nn khng th tng
hp DNA vi chnh xc cao v nh vy c th n khng phi l
polymerase chnh trong tng hp si ra chm. Polymerase c th hot
ng nh DNA polymerase I ca vi khun. Loi khng nguyn trong nhn
lm tng sinh t bo (proliferating cell nuclear antigen = PCNA) c vai tr
trong c ti bn ln sa cha. Mt trong cc chc nng ca n l dng
lm nhn t trt (processivity factor) cho DNA polymerase v .
PCNA gi DNA polymerase vi si khun tng hp DNA nhanh.
(iv) Ngoi ra cn c mt s enzyme v protein c th tham gia vo
khu kt thc ti bn, tng hp cc u mt (telomere) hoc tham gia ct
ni trong qu trnh ti t hp.
3. C ch ti bn DNA
Trong phn ny, chng ta tm hiu k c ch ti bn vi khun E. coli,
v nu mt t vn lin quan eukaryote m i din l DNA ngi.
3.1. Giai on khi u ca s ti bn (initiation of replication)
i vi nhim sc th E. coli, s ti bn bt u ti mt khi im
c th gi l Ori (hnh 5.18). Trong khi , trn mi nhim sc th
eukaryote c nhiu khi im ti bn hai hng nh th (hnh 5.19). Qa
trnh din bin ti khi im cho n lc hnh thnh hai chc c th tm
tt (theo Kelman v O'Donnell, 1994) nh sau: (1) Cc protein bm khi
im dnaA c tng hp bm Ori to ra cu trc nucleoprotein
chuyn ho ca khi im; (2) Sau , cu trc ny m xon vng DNA
giu AT hnh thnh "phc hp m" (open complex); v (3) Hai phn t
helicase dnaB chui vo phc hp m lm m xon khi im theo c hai
169
hng, to thnh hai chc ti bn (replication fork). Khi c hai si n

ca mi chc c tch ra th cc protein SSB bm vo. Nh vy cc si
n c dng lm khun hiu qu cho cc enzyme ti bn hot ng.
Khi u trong ti bn DNA l s tng hp mt on mi ngn bi
primase, m E.coli l phc hp primasome (th m u) nh ni
trn. Kch thc on mi cc sinh vt khc nhau l khng ging nhau,
v thng khng vt qu 12 ribonucleotide. E. coli, theo kt qu
nghin cu ca b Okazaki v cs (1985), on ny di 10-12 nucleotide.
Khi im ti bn
Cc u mt khng y
Hnh 5.19 Nhiu khi im ti bn (origins of replication) trn mt nhim

sc th eukaryote. y cng cho thy cc u mt (telomeres) khng c
tng hp y , c th l cc u 5'.
3.2. Giai an ko di (elongation)

Mt khi primosome tng hp xong mt mi, l lc s ko di chui
DNA mi bt u. E. coli, enzyme then cht cho qu trnh ny l DNA
polymerase III hon chnh (holoenzyme), mt phc hp gm mi
polypeptide khc nhau. Mi phn t cho mt si khun. S ko di trong
sut qu trnh tng hp DNA E. coli r rng l cn ti mt replisome
(th ti bn) do kt hp gia primasome v DNA polymerase III hon
chnh. Tc tng hp trung bnh l 1.000 nucleotide mi giy.
S ti bn DNA trn mi chc, nh ni trn, xy ra theo kiu na
gin on (semi-discontinuous). C th qu trnh nh sau (hnh 5.20):
Trn si khun dn u (3'5'): Trc tin, enzyme primase hay
primasome ch tng hp mt on mi RNA vi u 3'-OH t do. Sau ,
enzyme hon chnh DNA polymerase III (replisome) bt u ko di chui
DNA mi sinh trng theo chiu 5'3' mt cch lin tc.
170
Trn si khun ra chm

(5'3'): S ko di din ra khng
lin tc di dng cc on
Okazaki. Kch thc trung bnh
mi on Okazaki E. coli l
1.000 - 2.000 nucleotide;
eukaryote l 100-200; v ni chung
l 100-1.000 nucleotide. Qu trnh
ny i hi s "mi ha" nhiu ln
v c tnh chu k, vi s tham gia
ln lt ca bn enzyme nh sau:
(i) primase tng hp mt on mi
RNA; (ii) DNA polymerase III
hon chnh ko di on Okazaki;
(iii) DNA polymerase I va ct b
dn tng nucleotide ca on mi
va lp khong trng bng cch
ko di dn on Okazaki theo sau;
Hng
ti bn
chung
Si ra chm
Si dn u
Hnh 5.20 S ti bn na gin on trn mt chc.
(iv) DNA ligase hn lin khe h cn li gia hai on Okazaki k nhau

bng mt lin kt 3',5'-phosphodiester. Qu trnh c din ra lun phin nh
vy, v cui cng si DNA mi c tng hp tr nn di ra v lin tc.
Cn eukaryote, vai tr ca cc enzyme v protein tham gia vo giai on
ko di trn c hai si khun c phn tch trn.
3.3. Giai an kt thc (termination)
Do c im cu trc nhim sc th hai nhm prokaryote v
eukaryote l hon ton khc nhau, c bit l cu trc cc u mt nhim
sc th eukaryote c pht hin gn y (hnh 5.21), nn c ch kt thc
ti bn ca chng cng khc nhau.
3.3.1. Vn kt thc ti bn prokaryote
hon thnh vic ti bn DNA, t bo phi lp y cc khong trng
do cc RNA mi b ct b li. i vi cc DNA mch vng nh ca vi
khun chng hn, khng c vn lp tt c cc khong trng bi v bao
gi cng c u 3' DNA khc nm pha trc dng lm mi. Tht vy, c
hai chc ti bn c bt u t mt khi im duy nht (ori), v di
chuyn hu nh cng tc , theo hai hng i lp nhau xung quanh
nhim sc th mch vng cho ti khi chng gp nhau ti mt im kt
thc chung i din vi ori. Thc ra, theo Bastia v cs (1997) cng nh
171
nhiu tc gi khc, y l vng cha cc trnh t c th gi l cc im

kt thc ti bn (replication termini). V ti cc trnh t c th ny c cc
protein kt thc ti bn (replication terminator protein = RTP) bm vo v
cc phc hp protein-DNA ny ngn cn s di chuyn ca cc chc ti
bn theo mt cch phn cc hoc nh hng c th. S ngng li ca
cc chc ti bn ti vng kt thc to nn bc u tin trong qu trnh
hon thnh mt vng ti bn v sau , tch hai nhim sc th con ri ra
mt cch c trt t nh xc tc ca topoisomerase IV.
Lu : (1) Cc nghin cu gn y cho thy RTP ca E. coli c trng
lng phn t ~36kD, c m ha bi gene tus (ter) v trong mi t bo
c ~80 bn sao ca protein ny c duy tr hu nh n nh trong sut
chu k t bo. Cn RTP ca Bacillus subtilis l mt dimer c trng lng
phn t mi tiu n v l 14.500 kD, c m ha bi gene rtp. (2) Cc
trnh t nht tr (consensus sequences) ca vng kt thc ti bn E. coli
(R6K) v B. subtilis, theo Bastia v cs (1997), nh sau:
E. coli (R6K) 5'NN(A/T)(A/T)(A/T)G(A/T)(A/G)TGTTGTAACTA(A/C)NN3'
B.subtilis
5'ACT(A/G)AN(T/A)(A/G)(A/C)(A/T)(C/T)(T/A)(A/G)TG(T/A)AC/CTTCAN3'
3.3.2. Vn kt thc ti bn eukaryote

Nh chng ta u bit, mi nhim sc th eukaryote cha mt phn t
DNA si kp mch thng kt hp vi nhiu loi protein, c cc u mt
c trng gi l telomere. Mt khi an mi u tin trn mi si c
loi b th n khng c cch no b p li khong trng , bi v
DNA khng th no ni rng theo chiu 3'5', v cng chng c u 3'
(a)
(b)
Hnh 5.21 (a) nh chp cho thy cc u mt nhim sc th - telomeres c

mu vng c trng, v (b) s minh ha t chc ca telomere ngi.
nm pha trc nh trong cc DNA mch vng. Nu qu thc nh vy th

cc si DNA s ngn bt i sau mi ln ti bn. Vy cc t bo eukaryote
172
gii quyt vn ny nh th no?
Ko di
Chuyn dch
Ko di
Hnh 5.22 M hnh ca Carol Greider v c ch tng hp cc on lp

telomere trn si giu G nh telomerase Tetrahymena. T y c th hnh
dung cc bc tip theo: lp khong trng trn si i din giu C c thc
hin bi primase v DNA polymerase, v cui cng l ct b on mi.
Cc kt qu nghin cu u tin ca Elizabeth Blackburn v cc ng

s ca b gii p cho vn ny (hnh 5.22). Cc telomere khng
cha cc gene; thay v th chng c cu trc n gin gm nhng trnh t
ngn (6-8 cp base) lp li ni tip c ngn ln v c th cho tng loi.
Chng hn, Tetrahymena, mt nhm ng vt nguyn sinh c lng t,
n l (TTGGGG)n; Caenorhabditis: (CCCTCCC)n; bn Oxytrichia
thuc Euplotes: (CCCCAAA)n... Cn cc ng vt c v v ngi, n l
5'-TTAGGG-3' c lp li khong 1.000-2.000 ln (theo Yakoob v cs
1999, khong bin thin pht hin c trong cc t bo cc giai on
khc nhau l 150-2000 ln). Cc on lp ny c gn thm vo u 3'
ca cc si DNA, khng phi bng ti bn bn bo ton, m bng mt
enzyme gi l telomerase. Nu nh telomerase khng cho php mt c
ch ti bn bn bo ton, th n khng th s dng mt si DNA lm
173
khun cho si kia. Blackburn cho thy rng tnh cht c th ny nm

ngay trong chnh bn thn telomerase, v do mt RNA nh trong enzyme.
Nh vy, telomerase l mt ribonucleprotein v l mt enzyme phin m
ngc (reverse transcriptase), tng hp DNA t mt khun RNA. Chng
hn, telomerase ca Tetrahymena c mt RNA di 160 nucleotide c cha
trnh t 3'-CAACCCCAA-5' lm khun cho tng hp cc on lp 5'TTGGGG-3' trong cc telomere ca Tetrahymena (hnh 5.22); ngi,
phn t RNA trong telomerase di khong 450 nucleotide c cha trnh t
3'-AAUCCC-5' (nm trong on ng vi v tr 46-56) lm khun cho tng
hp cc on lp telomere 5'-TTAGGG-3' trn cc si n c u mt 3'.
Sau , si i din, DNA polymerase c th hon thnh vic tng hp
"cc u mt khng y " (incomplete ends) trn si i din sau khi
c mi ha bn trong cc telomere ; v cui cng on mi s b ct
b v khe h c ni li.
Cc nghin cu gn y cho thy rng: enzyme telomerase ch c mt
trong cc t bo mm (germ cells), k c cc t bo gc ca phi
(embryonic stem cells); cc t bo ung th (cancer cells); v cc eukaryote
n bo nh Tetrahymena thermophila. Trong khi , cc t bo soma
bnh thng ca ng vt c v khng thy c telomerase.
iu cho php l gii ti sao cc t bo mm cng nh cc t bo
ung th c kh nng phn chia gn nh l v hn; hay ni cch khc,
telomerase v s duy tr chiu di telomere chnh l cha kha cho s bt
t ca t bo. Ngc li, hu qu ca s vng bng telomerase trong cc
t bo soma (do gene m ha n bt hot) l ch: c sau mi ln nguyn
phn (mitosis), tt c 92 telomere ca cc t bo soma ngi ng lot
mi ci b mt i chng 100 cp base, ngha l khong 16 on lp
TTAGGG. Theo l thuyt, vi tc ny th sau 125 ln nguyn phn cc
telomere s bin mt hon ton. Trn thc t, cc th nghim khc nhau k
t khm ph u tin ca Leonard Hayflick vo u thp nin 1960 cho
n nay (Greider v Blackburn 1996; Hayflick 1997; Shay v cs 2004; ...)
xc nhn rng: ch sau khong 30-50 ln nguyn phn, cc t bo soma
mt hn kh nng phn chia v i vo giai on lo ha (senescence) v
cht t nhin. Ci c gi l gii hn Hayflick (Hayflick limit).
Chnh qu trnh rt ngn telomere theo thi gian (ngha l s ln
nguyn phn) nh th khin ngi ta lin tng ti s tn ti ca ci gi l
"ng h di truyn cho s lo ha" (genetic clock for aging), v bt u
tin hnh cc nghin cu v "hiu ng v tr telomere" (telomere position
effect = TPE) (Borek 2002). l l do ti sao cc t bo soma c s ln
phn chia hu hn trc khi chng cht v cng l l do ti sao tt c
174
chng ta cng nh mi sinh vt u phi cht. Nh th, ci cht tt yu

trn phng din sinh hc, ci cht t nhin ca thn xc c l gii
kh r rng v y . V t cc nghin cu ny m ra trin vng to
ln cho liu php ung th (cancer therapy) cng nh vn lo ha v
bnh tt pht sinh t con ngi (Greider v Blackburn 1996;Yakoob
v cs 1999; Borek 2002; Shay v cs 1998, 2004).
VI. Ti bn ca cc b gene RNA (RNA genomes)

1. c im ti bn ca cc b gene RNA virus v hu qu ca chng
cc virus c b gene RNA, phng thc ti bn ca chng r rng l
khc vi cc h thng ti bn DNA bit. Trc ht, cc enzyme tng
hp RNA khng cn c mi (primer), v vy khng c c hi cho vic c
sa (proofreading). Ngoi ra, v mt di truyn RNA l mt phn t km
bn vng so vi DNA bi v nhm hydroxyl c mt nguyn t C2' ca
gc ng cho php ct t (thy phn) lin kt phosphodiester gia hai
ribonucleotide v to thnh dng phosphodiester vng gia cc nhm
hydroxyl ca C2' v C3' trong cng mt gc ng; sau cu trc vng
ny m ra v li nhm phosphate v tr C3'. S kt hp ca hai c
im trn l nguyn nhn lm hn ch kch thc cc b gene RNA. Cc
b gene ny khng th sinh trng qu ln, hoc khng th trnh khi t
l sai st cao trong qu trnh ti bn (10-3-10-4). V vy, trn thc t, b
gene RNA ln nht c bit l mt RNA si n vi chng 29.600 base.
l trng hp ca virus gy bnh st vim phi cp (SARS) thuc h
coronavirus c pht hin hi thng 3/2002 ti mt s nc chu ,
Canada... cng l l do ti sao cc virus RNA cho nhiu bin th khc
nhau n nh vy, mc d kch thc b gene u c ln. iu ny lm
cho cc virus RNA thc s tr thnh mi him ha bi v chng c th
tin ha nhanh xm nhp vo cc h thng min dch ca vt ch.
Chng hn, cc b gene HIV c nhiu bin th gy kh khn cho vic bo
ch cc vaccine v thuc chng li tt c cc bin th ca HIV.
Di y nu khi qut v hai kiu ti bn ca cc virus RNA.
2.Ti bn ca b gene RNA
Kiu truyn thng tin trc tip t RNA sang RNA xy ra trong cc t
bo ly nhim virus RNA nh: virus m thuc l v nhiu virus thc vt
khc, k c cc phage RNA nh MS2... B gene RNA ca cc virus ny
c mang gen m ho enzyme ti bn c th. Sau khi c tng hp trong
t bo ch, enzyme ny s dng bn thn RNA virus lm khun tng
hp cc phn t RNA b sung. n lt mnh cc RNA li lm khun
tng hp tr li cc phn t RNA ca cc virus th h con .
175
3. Phin m ngc
Phin m ngc (reverse transcription) l kiu truyn thng tin t
RNA sang DNA, ch xy ra trong cc t bo ng vt v ngi b ly
nhim bi mt s virus mang mt si RNA c kh nng gy khi u hoc
hai si RNA nh trng hp HIV chng hn. Trn mi si RNA li ca
cc virus ny c mang mt enzyme phin m ngc (reverse
transcriptase). Khi xm nhp vo t bo ch, enzyme ny s dng RNA
ca virus lm khun tng hp si DNA b sung (complementary DNA
= cDNA). Sau , si cDNA ny c th lm khun tng hp tr li b
gene ca virus (cDNARNA), hoc tng hp ra si DNA th hai b sung
vi n (cDNADNA) nh trong trng hp virus gy khi u m kt qu
l to ra mt cDNA si kp. Phn t DNA si kp c tng hp trc
tin trong qu trnh ly nhim c th xen vo DNA ca vt ch v trng
thi tin virus (provirus). V vy, provirus c truyn li cho cc t bo
con thng qua s ti bn ca DNA vt ch, ngha l cc t bo con chu
ca vt ch cng b chuyn sang tnh trng c mm bnh ung th. Cc t
bo ung th ny mt kh nng kim sot s sinh trng - phn chia in
hnh ca t bo bnh thng; chng tng sinh rt nhanh v to ra khi u
(tumor). chnh l c ch gy ung th bi virus.
Ngy nay, ngi ta c th tinh chit cc enzyme phin m ngc
phc v cho k thut to dng cDNA ti t hp (chng 10).
Cu hi v Bi tp
1. Trn c s cc c im ca m hnh Watson-Crick, hy cho bit: (a)
M hnh ny cho php gii thch cc quy lut Chargaff nh th no? (b) C
s ca c tnh i song song trong chui xon kp DNA l g? (c) M hnh
ny gi ln kh nng t ti bn ca DNA ra sao?
2. Hy xc nh hm tng i (%) ca cc nucleotide trong DNA ca
ngi, c hi (Salmo salar) v g (Gallus domesticus). Bit rng t l
(A+T)/(G+C) tng ng ca cc loi ny l 1,52; 1,43; v 1,34.
3. Da vo cu trc ha hc lp th ca cc base (A,T,G v C), hy
gii thch: (a) Ti sao trong ADN ch tn ti hai kiu kt cp A-T v G-C
m khng c cc kiu khc? (b) Cc kiu kt cp A-C v G-T c th xy
ra khi no v gy ra hu qu g? Gii thch v cho cc s minh ha.
4. Gi s t l (A+T)/(G+C) mt si ca chui xon kp ADN l
0,25. (a) Hy cho bit t l ny trn si b sung v trn c phn t? (b)
Nu cho rng 0,25 l ca t l (A+G)/(T+C), th t l ny trn si b sung
176
v trn c phn t s nh th no?

5. Hy ch ra nhng im ging nhau v khc nhau gia prokaryote v
eukaryote v cc vn sau: (a) Khi im ti bn; (b) Cc enzyme tham
gia ti bn; v (c) Cc c ch m u, ko di, v kt thc ti bn.
6. Da vo hiu bit v thuyt di truyn nhim sc th, hy gii thch
th nghim Griffith v s bin np ph cu khun S. pneumoniae.
7. So snh cu trc ca cc nucleotide v cc chui polynucleotide
cng nh cu trc phn t ca DNA v RNA.
8. Th no l bin tnh v hi tnh ca DNA? Cc hin tng ny c
ngha nh th no i vi cc b gene sinh vt v k thut di truyn?
9. Th no l gi tr C (C-value) v nghch l gi tr C (C-value
paradox)? Cho th d v nu ngha v mt l lun ca hiu bit ny.
10. S ti bn ca cc b gene RNA mt s virus khc vi cc h
thng ti bn DNA nhng im no? Ti sao kch thc cc b gene
RNA thng nh, nhng chng li c kh nng gy nguy him thc s i
vi cc vt ch? Hy gii thch mt c ch gy ung th bi virus.
Ti liu Tham kho

Ting Vit
H Hunh Thy Dng. 1997. Sinh hc Phn t. NXB Gio Dc.
Phm Thnh H. 2000. Di truyn hc. Ti bn ln II, NXB Gio Dc.
Phan C Nhn. 2001. Di truyn hc ng vt. NXB Khoa hc v K
thut, H Ni.
Phan C Nhn. 1999. Cng ngh ADN ti t hp. Trong: Di truyn hc
tp II (Phan C Nhn, ch bin). Trang: 257-303. NXB Gio Dc, H Ni.
Hong Trng Phn. 1995. Mt s vn v Di truyn hc hin i (Ti
liu BDTX cho gio vin THPT chu k 1993-1996). Trng HSP Hu.
Hong Trng Phn. 1997. Di truyn hc Phn t. NXB Gio Dc.
Watson JD. 1968. Chui xon kp: Hi k v vic pht minh ra cu trc
ca DNA. (Bn dch ca L nh Lng v Thi Don Tnh). NXB Khoa
hc v K thut, H Ni, 1984.
Ting Anh
Alberts B, Johnson A, Lewis J, Raff M, Robert K, Walter P. 2002.
Molecular Biology of the Cell. Garland Science, NY.
Bastia D, Manna AC, Sahoo T. 1997. Termination of DNA replication in
177
prokaryotic chromosomes. In: Genetic Engineering, Vol. 19. (Setlow JK

ed.) pp 101-119. Plenum Press, New York, USA.
Borek C. 2002. Telomere Control and Cellular Aging:
http://www.lef.org/magazine/mag2002/oct2002 report telo 01.html.
Donovan S and Diffley JFX. 1995. Replication origins in eukaryotes. In:
Current Opinion in Genetics & Development (Herr W and Kingston R,
eds.),Vol.5(2): 203-207. Current Biology Ltd, UK.
Greider CW and Blackburn EH. 1996. Telomere, Telomerase and Cancer.
Scientific American, 2/96, p.92: http://www.genethik.de/telomerase.htm.
Hamlin JL and Dijkwel PA. 1995. On the nature of replication origins in
higher eukaryotes. In: Current Opinion in Genetics & Development (Herr
W and Kingston R, eds.),Vol.5(2): 153-161. Current Biology Ltd, UK.
Harley CB, Villeponteau B. 1995. Telomeres and telomerase in aging and
cancer. In: Current Opinion in Genetics & Development (Herr W and
Kingston R, eds.),Vol.5(2): 249-255. Current Biology Ltd, UK.
Hayflick L. 1997. Mortality and Immortality at the Cellular Level. A
Review. Copyright 2005BioProtNetwork:webmaster@ protein.bio.msu.su.
Kelman Z, O'Donell M. 1994. DNA replication: enzymology and
mechanisms. In: Current Opinion in Genetics & Development (Stillman B
and Green M, eds.),Vol.4(2): 185-195. Current Biology Ltd, UK.
Lingner J and Cesh TR. 1998. Telomerase and chromosome end
maintenance. In: Current Opinion in Genetics & Development (Allis CD
and Gasser SM, eds.),Vol.8(2): 226-232. Current Biology Ltd, UK.
Price CM. 1999. Telomeres and telomerase: broad effects on cell growth.
In: Current Opinion in Genetics & Development (Kadonaga JT and
Grunstein M, eds.),Vol.8(2): 218-224. Current Biology Ltd, UK.
Shay JW and Wright WE. 1998. Teleomerase, Cellular Senescence and
Cancer. Page maintained by: Cell Biology and Neuroscience.
Shay JW. 2002. Telomeres, Aging, and Tumorigenesis. Gac Md Mx
Vol.138 Suplemento No.1, 2002, pp.S2-S3.
Shay J, Schneider E, Masoro EJ. 2004. Is there a genetic clock for aging?:
www.infoaging.org/b-tel-home.html.
178
Twyman RM. 1998. Advanced Molecular Biology. BIOS Scientific

Publishers Ltd/ Springer-Verlag Singapore Pte Ltd.
Watson JD, Hopkins NH, Roberts JW, Steitz JA, Weiner AM. 1987.
Molecular Biology of the Gene. 4th ed, Benjamin/Cummings Publishing
Yakoob J, Hu G-L, Fan X-G, Zhang Z. 1999. Telomere, telomerase and
digestive cancer. World Journal of Gastroenterology, 5(4):334-337.
Mt s trang web
http://www.lef.org/magazine/mag2002/oct2002 report telo 01.html.
http://www.genethik.de/telomerase.htm.
http://www.infoaging.org/b-tel-home.html.
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/
http://www.ornl.gov/hgmis
http://www.horizonpress.com/pcr/
http://dir.niehs.nih-gov/dirlmg/repl.html
179
Chng 6
Gene v Qu trnh Sinh tng hp Protein

Gene, n v thng tin c truyn t cha m cho con ci, l khi nim
then cht ca di truyn hc. Ni n gene tc l ni n DNA v cc quan
h ca n vi RNA v protein di dng s sau y, c gi l L
thuyt trung tm (Central Dogma) ca Sinh hc Phn t (hnh 6.1).
Trong cc si n ca
DNA c dng lm khun cho
ti bn (replication; nh xt
Ti bn
chng 5). Mt khc, tng an
xc nh ca n (tc cc gene) c
Phin m
th lm khun cho s tng hp
cc RNA trong mt qu trnh gi
l phin m (transcription). n
Dch m
lt, cc phn t RNA ny li lm
khun cho s tng hp cc chui
polypeptide m t to thnh
cc protein; qu trnh ny c
Hnh 6.1 L thuyt trung tm ca Sinh hc Phn t
gi l dch m (translation), bi v n chuyn bc thng tin di dng cc

nucleotide thnh ra sn phm c xy dng bng cc amino acid. Hai
qu trnh sau c coi l hai giai an chnh trong s biu hin ca gene
m ha protein (protein coding gene). Thc ra, s biu hin ca mt gene
chu s kim sot nhiu cp khc nhau (chng 7).
Trong chng ny, chng ta s ln lt tm hiu s pht trin ca khi
nim gene, cu trc v chc nng protein - sn phm ca gene, bn cht
ca m di truyn, v cc qu trnh phin m v dch m.
I. S pht trin ca khi nim gene

1. Cc quan nim ca Mendel v Morgan v gene
Mendel l ngi u tin nu ln nh ngha v gene nm 1865 (thut
ng ny c Johannsen a ra nm 1909). Theo , gene l n v di
truyn tn ti dng ht ring bit, xc nh mt tnh trng c th trong
cp tnh trng tng phn. y mi ch l s suy lun thun ty, khng c
c s vt cht c th.
Quan nim chnh xc hn v c s vt cht v chc nng ca gene ny
180
sinh t nhiu ngun nghin cu c lp nhau trong sut 50 nm u ca

th k XX. Trng phi Morgan sau khi xc nh cc gene nm trn
nhim sc th v xut phng php lp bn gene bng ti t hp,
khng nh rng cc gene l nhng n v c s v khng chia nh ca vt
cht di truyn v c cu trc ln chc nng; chng lin kt vi nhau theo
kiu thng hng trn nhim sc th.
2. Gi thuyt mt gene - mt enzyme ca Beadle v Tatum
Mt hng nghin cu khc tp trung vo phng din chc nng sinh
ha ca gene. Nm 1902, Archibald Garrod gi rng ri ln chuyn ha
alkapton niu (alcaptonuria) bt ngun t mt sai hng ca mt enzyme
c th v c di truyn theo kiu ln nhim sc th thng, m ng gi
l sai st chuyn ha bm sinh. n nm 1941, Beadle v Tatum mi lm
sng t tng trn bng cc th nghim gy t bin bng tia X
Neurosporora. gii thch cc tn thng sinh ha c th do t bin,
h xut "gi thuyt mt gene - mt enzyme" ni ting; n c xem
nh l m hnh v chc nng ca gene, m ng cho s ra i ca di
truyn sinh ha. V sau, quan nim "mt gene - mt enzyme" c m
rng thnh "mt gene - mt protein", v tip tc chnh xc ha bng mnh
"mt gene - mt polypeptide".
Tht vy, t khi Avery v cc ng s chng minh DNA l vt cht
mang thng tin di truyn vo nm 1944, v c bit l sau khi Watson v
Crick khm ph ra cu trc phn t DNA nm 1953, quan nim v gene
khng ngng c pht trin v chnh xc ha. V mt cu trc, gene l
mt on xc nh ca b gene (DNA hu ht sinh vt v RNA mt
vi virus). V phng din chc nng, nh chng ta r, khng phi mi
gene u m ha cc enzyme m mt s m ha cc polypeptide vi cc
chc nng khc nhau, v mt s m ha cc phn t RNA chc nng nh
RNA ribosome (rRNA) v RNA vn chuyn (tRNA). Hn na, thng tin
trong gene c th c s dng mt cch c chn lc sinh ra nhiu hn
mt loi sn phm (cc gene phn on). Trc tin, ta hy tm hiu cng
trnh nghin cu ca Benzer v cu trc tinh vi ca gene.
3. Quan nim ca Benzer v cc n v cu trc v chc nng di truyn
Cc cng trnh nghin cu ca Seymour Benzer (t 1957 n 1961) v
ti t hp phage T4 cho thy rng, gene theo quan nim ca Morgan
c th chia nh thnh cc n v nh hn. ng a ra cc thut ng
muton, recon v cistron nh ngha cc n v khng chia nh tng
ng l t bin, ti t hp v chc nng. Bng cch lai cc th t bin
ca cng mt gene c ngun gc c lp nhau trong khi cho ly nhim
phage, lm xut hin phage kiu di. iu ny ch c th xy ra bi s
181
ti t hp bn trong gene (intragenic recombination), nu nh cc phn

nh ring bit ca gene u b t bin. iu ny chng t rng gene b
phn chia thnh cc n v nh hn thng qua ti t hp v dt bin. Tuy
nhin, v kch thc ca muton v recon c coi l tng ng vi mt
cp nucleotide, cho nn ngy nay t thn hai n v ny khng cn gi tr
s dng na.
Thut ng cistron ca Benzer c ngha l n v chc nng di truyn
khng chia nh. iu ny c th xc nh bng s phn tch b sung
(complementation analysis), trong gene m c th l sn phm ca n
c trc nghim v kh nng b p cho mt t bin ti mt gene tng
ng trong cng t bo. S b sung lin tip lm phc hi kiu hnh di.
cistron 1
cistron 2
cistron 1
Kiu di
(b)
cistron 1
cistron 2
P Kiu di
(c)
(a)
cistron 2
P Kiu di
cistron 1
X
cistron 2
Th t
bin
(d)
Hnh 6.2 S minh ha trc nghim cis-trans: (a) con ng chuyn ha

bnh thng; (b) trc nghim cis; (c) v (d) trc nghim trans. Ch thch: S-c
cht (subtrate); I- sn phm trung gian (intermediate); P- sn phm cui cng
(product), y l sc t c trng cho kiu hnh di; cc mi tn () ch cc
enzyme sn phm sinh ra t cc cistron 1 v cistron 2.
C s ca phn tch b sung l trc nghim cis-trans (cis-trans test),

m t y ny sinh ra thut ng cistron, trong cc cp t bin bt
ngun c lp c xt cc cu hnh cis (u) v trans (lch). Trc
nghim cis c dng lm i chng, v nu nh c hai t bin u c
mt trong mt b gene th b gene kia phi l kiu di c hai locus v
sinh ra cc sn phm gene bnh thng, do cho ra kiu hnh di (hnh
6.2b). Trc nghim trans l php th b sung v xc nh gi hn ca n
v chc nng. Nu nh cc t bin nm trong cc gene khc nhau, khi
chng c mt cu hnh trans, mi mt b gene c th b sung sn phm
182
m gene kia khng to ra c. Khi c tt c cc sn phm gene cn

thit th t bo l kiu di (hnh 6.2c), ngha l c s b sung dng tnh
(positive complementation). Nu nh c hai t bin thuc cng mt gene,
khi chng c mt cu hnh trans, th mi mt b gene c th mang mt
bn sao t bin ca gene v khng c sn phm hot ng chc nng
c to ra trong t bo, ngha l khng c s b sung (hnh 6.2d).
S phn tch b sung vi khun v nm men bia cng ch ra rng gene
l mt cistron, ngha l gene c nh ngha nh l mt n v chc
nng. Phng php ny t ra hu ch cho vic khng nh chc nng ca
gene, xc nh s lng cng nh trt t hot ng ca cc gene trong mt
con ng chuyn ha no .
Vy cistron l g? Cistron l mt on xc nh ca DNA (hay b gene
ni chung) mang thng tin cu trc ca mt polypeptide c th m gii
hn ca n c xc nh bng trc nghim cis-trans. Kch thc trung
bnh ca mt cistron l 1.200 cp base. Nh vy, cistron chnh l gene cu
trc theo ngha hp hay gene m ha protein.
Mt cch tng i, theo ngha rng, c th nh ngha gene l mt
an xc nh ca b gene m ha thng tin ca mt polypeptid hoc mt
phn t RNA chc nng (nh tRNA, rRNA...).
Tuy vy, nh ngha ny khng th bao gm y chc nng v cu
trc ca gene trong ton b sinh gii, bi v cc chin lc cho s biu
hn gene v t chc b gene cc vi khun v eukaryote l rt khc nhau.
4. Mi quan h gene - cistron cc prokaryote v eukaryote
4.1. S tng ng gene - cistron cc b gene n gin
cc prokaryote v eukaryote bc thp, thng c mt mi quan h
n gin gia gene v sn phm ca n.Trong hu ht trng hp, c mt
s tng ng mt gene - mt sn phm, v s ng tuyn tnh gia gene
v chui polypeptide ca n c Ch.Yanofsky xc nhn nm 1961. V
vy cc sinh vt ny, gene v cistron l tng ng: gene l n v
chc nng di truyn, mang thng tin di truyn c biu hin trn vn.
(a)
(b)
Hnh 6.3 (a) vi khun, cc gene thng c sp xp trong mt operon

v c phin m thnh mt phn t mRNA a cistron. (b) eukaryote,
cc gene tn ti ring bit di dng n cistron.
183
Cng cn lu rng, vi khun, cc gene ng ngha vi vng m

ha hay khung c m (open reading frame = ORF), trong khi cc
eukaryote n ng ngha vi n v phin m (transcription unit). l do
cc gene vi khun thng c sp xp trong mt operon (chng 7), v
th c nhiu sn phm c dch m t mt mRNA a cistron (polycistronic mRNA; hnh 6.3a). Tri li, cc eukaryote, hu ht cc gene c
phin m di dng mRNA n cistron (monocistronic mRNA; hnh 6.3b).
4.2. S khng tng ng gene - cistron cc b gene phc tp
cc b gene eukaryote bc cao, thng thng c mt mi quan h
phc tp gia gene v sn phm ca n (hnh 6.4). Hu ht cc gene ca
eukaryote bc cao u c cha cc intron (intervening sequences), tc cc
on khng m ha protein, nm xen gia cc exon (expressed
sequences), cc on m ha protein. Cc gene nh vy c gi l gene
phn on (split gene) hay gene t qung (interrupted gene); n c
pht hin ln u tin bi Phillip Sharp vo nm 1977 (hnh 6.4).
(a)
(b)
(c)
Hnh 6.4 nh hin vi in t v hnh m phng vic s dng vt d mRNA
t bo cht c nh du pht hin gene phn on (a v b); m t vn tt
s tng hp pre-mRNA v ct b cc intron to ra mRNA trng thnh
t mt gene phn on c cha hai intron (c).
Cc khm ph v sau ny cn cho thy nhng s kin rc ri ny sinh

trong cc gene phn on ny, ch: thng tin trong gene c s dng
mt cch chn lc sinh ra nhiu sn phm khc nhau, gi l ct-ni c
chn lc (alternative splicing) v.v. Cc sn phm c quan h v cu trc
(v d, calcitonin/CGRP) thng c cc chc nng khc nhau. V l ,
cistron i khi c xem l tng ng vi exon ca gene eukaryote, v
gene phn on c xem nh l mt chui cc cistron gi nhau (Twyman
1998). Ngoi ra, c vi trng hp trong cn ti hai gene sinh ra
mt sn phm mRNA n thng qua kiu ct-ni cho (trans-splicing)
184
hoc bin tp RNA (RNA editing). Chng hn, khm ph mi nht cho
thy glucose 6-phosphate dehydrogenase l mt enzyme c mt trong cc
t bo hng cu ngi; n bao gm hai dng nh/th yu v ln/chnh yu
(minor and major form); dng u c trnh t cc amino acid thuc gene
trn nhim sc th X; v dng sau gm hai peptide c m ha t thng
tin ca hai nhim sc th, cc amino acid trong on 1-53 c m ha
trn nhim sc th s 6 v cc amino acid on tip theo 54-479 c
m ha trn nhim sc th X (theo McClean 1998). Tt c nhng trng
hp ny ni ln mt iu rng, a ra mt nh ngha chnh xc v gene
khng h n gin t no. Tuy nhin, nhn ton cc th mt khi nim
thng nht ni bt l, tt c cc sinh vt t vi khun E. coli cho n con
ngi u c chung h thng mt m di truyn v c chung phng thc
'chuyn ti' thng tin trong gene thnh ra protein.
4.3. Cc thnh phn cu trc hay l t chc ca mt gene
T chc ca mt gene c th bao gm cc vng ring bit vi cc chc
nng c th (Bng 6.1; theo Twyman 1998, c sa i).
Bng 6.1 Cc thut ng c dng ch cc phn chc nng ca cc gene
Thut ng
Allele
Cistron
Vng m ha, khung
c m (ORF)
Gene phn on
Gene
Locus gene
Operon
Pseudogene
on m c
nh ngha
Mt bin th v trnh t ca mt gene (hoc marker
di truyn khc, v d: trnh t RFLP, VNTR).
Mt n v chc nng di truyn, mt vng ca DNA
m ha mt sn phm c th.
Mt vng ca DNA c dch m thnh protein. vi
khun, l m gene. eukaryote, vng m ha
c th b gin an bi cc intron.
Mt gene m ha protein gm cc on khng m ha
(intron) nm xen k gia cc om m ha (exon).
vi khun, mt n v chc nng di truyn m ha
hoc l 1 polypeptide ring hoc phn t RNA.
eukaryote, 1 n v phin m c th m ha 1 hay
nhiu sn phm hoc ng gp vo 1 sn phm.
V tr ca mt gene trn mt nhim sc th, k c cc
yu t iu ha k bn. Thut ng locus c dng
theo cch ring ch v tr ca gene-marker bt
k, yu t iu ha, khi im ti bn, v.v..
Mt locus ca vi khun c cha nhiu gene (m c
phin m nh l mt bn sao polycistron n) v
cc yu t iu ha chung ca chng.
Mt trnh t khng hot ng chc nng vn c cu
trc tng t mt gene hot ng chc nng.
Bt k phn no ca n v phin m ca 1 gene RNA
185
phin m
n v phin m,
vng c phin m
Vng khng c
dch m (UTR)
Gene b phn chia
(divided gene)
hay operon gene RNA s b loi b trong khi to ra

cc phn t RNA trng thnh.
Mt vng ca DNA c phin m thnh RNA. cc
eukaryote, l mt gene. vi khun, n c th
bao qut nhiu gene.
Bt k phn no ca n v phin m m khng c
dch thnh protein. Cc UTR k bn mt vng m
ha hay operon c gi l cc UTR 5' v 3'.
Mt gene phn an vi cc exon cc locus ring
bit c phin m ring r v khu ni li bi s
ct-ni cho. Thc ra l cch gi sai v mi
locus ng ra phi c coi nh l 1 gene ring.
bt k locus no, mt vng DNA c phin m c th gi l mt

n v phin m (transcription unit). Nh cp, prokaryote, mt n
v phin m c th gm nhiu gene; trong khi eukaryote, cc n v
phin m hu nh bao gi cng tng ng vi mt gene n.
Hnh 6.5 Cu trc in hnh ca mt gene eukaryote.
i vi cc gene m ha protein, r rng l c mt s tch bit gia

vng c dch m thnh chui polypeptide v vng khng c dch m.
vi khun, vng c dch m l khung c m (ORF), trong cc gene
phn cch nhau bng cc on m (spacer) c gi l cc vng khng
m ha bn trong (internal noncoding region). Cc gene nm hai u
ca mt operon cng c km bi mt vng khng m ha c tn l
vng khng dch m 5' (5' untranslated region = 5' UTR) hay on dn
u (leader sequence) v vng khng c dch m 3' (3' UTR) hay on
ko sau (trailer sequence). V bn cht, chng l cc on iu ha; chng
hn, vng 5'UTR kim sot s bm vo ca ribosome, cn vng 3'UTR
thng ng vai tr quan trng trong s n nh mRNA. cc gene
eukaryote, vng m ha cng c km bi cc vng UTR iu ha, v c
hai vng UTR 5' v 3' cng nh khung c m c th b gin on bi cc
on khng m ha (tc cc intron) m chng s c ct b trc khi
xut mRNA trng thnh ra khi nhn. Nh th, bt k on no m rt
cuc b loi b khi pre-RNA th c gi l cc on m c phin m
(transcribed spacer). Cu trc in hnh ca cc gene m ha protein
prokaryote v eukaryote c ch ra tng ng hnh 6.3a v hnh 6.5.
186
II. Cu trc v chc nng ca protein

1. Cu trc protein
Cc protein l nhng polymer sinh hc c cu to bng cc amino
acid ni kt vi nhau bng cc lin kt peptide. C 20 loi L--amino acid
c pht hin trong cc protein ca cc t bo (hnh 6.6). V cu trc, ni
chung, mi amino acid gm c mt nguyn t carbon alpha (C) v tr
A
Hnh 6.6 Hai mi loi amino acid pht hin c trong cc protein, vi
bn nhm: A. Cc amino acid c chui bn tch in dng (3 bn tri) v m
(2 bn phi); B. Cc amino acid c chui bn khng tch in; C. Cc trng
hp c bit; v D. Cc amino acid c chui bn k nc.
187
trung tm, nh xung quanh n l mt nhm amin (-NH2), mt nhm

carboxyl (-COOH), mt nguyn t hydro (-H) v mt gc R hay chui bn
c trng cho tng loi amino acid (hnh 6.7a). Khi trng thi dung dch,
cc nhm amin v carboxyl thng phn ly thnh trng thi ion, tng
ng l +H3N- v -COO. Hai amino acid ni vi nhau bng mt lin kt
peptide (CN) gia nhm carboxyl ca amino acid ny vi nhm amin
ca amino acid k tip v loi tr mt phn t nc; c nh th cc amino
acid kt ni vi nhau to thnh mt chui gm nhiu amino acid, thng
c gi l polypeptide (hnh 6.7b). Mi chui polypeptide lun lun c
chiu xc nh +H3N COO (do tc dng ca enzyme peptydyltransferase) v c c trng v s lng, thnh phn v ch yu l trnh
t sp xp ca cc amino acid (hay cn gi l cu trc s cp, cu trc
quan trng nht ca tt c cc protein do gene quy nh).
(a)
(b)
Hnh 6.7 (a) Cu trc chung ca mt amino acid; (b) s hnh thnh chui
polypeptide, cu trc s cp ca tt c cc protein.
C bn mc cu trc ca cc protein c trnh by hnh 6.8. Trt

t sp xp thng hng ca cc amino acid to thnh cu trc bc I
(primary structure) ca protein. Cch thc cc amino acid ny tng tc
vi cc amino acid ln cn bng cc mi lin kt hydro hnh thnh nn cu
trc bc II (secondary structure) ca protein; hai dng ph bin ca cu
trc bc II l: chui xon alpha (-helix) v tm beta (-pleated sheet).
Cn hnh dng khng gian ba chiu ca mt chui polypeptide chnh l
cu trc bc III (tertiary structure) ca n; hu ht cc protein u ly
dng ny m ta gi l hnh cu (globular). V nhiu protein c cu trc
gm hai hoc nhiu polypeptid cng hp nht trong mt protein phc tp,
gi l cu trc bc IV (quaternary structure). y l mc cu trc cao nht
ca protein; chng thng cha nhiu vng cu trc cun cht gi l cc
domain, nh trong hemoglobin hoc cc khng th (xem hnh 6.9).
2. Chc nng protein
Ni chung, protein l cc hp cht hu c lm nn s sng vi nhng
chc nng thit yu khc nhau sau y:
(i) Cc protein l thnh phn cu to c s ca cc t bo, bao gm
188
cc mng t bo, cc bo quan, b my di truyn ca chng. cng l

cc protein dng si lm thnh cc c quan b phn trn c th cc ng
vt, nh: collagen lm nn xng, sn, gn v da; keratin cu to nn cc
lp ngoi cng ca da v tc, mng, sng v lng;
(ii) Cc enzyme ng vai tr xc tc cho tt c cc phn ng ha hc
trong t bo v c th u l nhng protein hnh cu. Quan trng nht l
cc enzyme tham gia vo cc con ng chuyn ha v cc enzyme tham
gia vo cc qu trnh truyn thng tin di truyn trong t bo.
Cu trc protein bc I l trnh t sp xp ca
cc amino acid trong mt chui polypeptide.
y l bc cu trc c s quan trng nht ca
tt c cc protein do gene trc tip quy nh.
Cc amino acid
Tm beta
Xon alpha
Cu trc protein bc II xy ra khi trnh t cc
amino acid trong mt chui polypeptide ni vi
nhau bng cc lin kt hydro. Cu trc ny c
hai kiu c bn, l: chui xon alpha (theo
chiu xon tri) v tm beta (dng gp np).
dng tm beta, hai chui polypeptide i song
song xp cnh nhau; in hnh l cc si t.
Tm beta
Cu trc protein bc III xy ra khi cc lc
hp dn no c mt gia cc vng xon
Xon alpha v cc tm beta gp np trong mt chui
alpha polypeptide, hnh thnh nn mt cu trc cun
gp c dng khi cu. Mt s protein chc
nng c cu trc kiu ny, nh myoglobin...
Cu trc protein bc IV l mt protein gm
hai hoc nhiu chui popeptide cng loi hoc
khc loi kt hp vi nhau. C kh nhiu
protein chc nng c kiu cu trc ny; mt s
nh hemoglobin v chlorophyll, trong thnh
phn cn c ion tng ng l Fe++ v Mg++.
Hnh 6.8 Bn bc cu trc ca protein.
189
Hnh 6.9 Cu trc bc IV in hnh ca hemoglobin, tubulin v immunoglobulin. y cho thy s chui polypeptide v c bit l cc vng chc nng
c trng ca hemoglobin v khng th immunoglobulin kiu IgG.
(iii) Cc hormone protein bt ngun t cc tuyn ni tit th khng

hot ng nh cc enzyme. Thay cho s kch thch cc c quan ch,
chng li khi u v kim sot cc hot ng quan trng, v d nh tc
chuyn ha v sn xut ra cc enzyme tiu ha v sa. Insulin c tit
ra t cc o Langerhans tuyn ty, iu ha s chuyn ha carbonhydrate bng cch kim sot cc mc glucose trong mu. Thyroglobulin (t
tuyn gip) iu ha cc qu trnh chuyn ha ni chung; calcitonin cng
t thyroid lm h thp mc calcium trong mu v.v.
(iv) Cc khng th (antibodies) trong h thng min dch, cn gi l
cc immunoglobulin, lm ra hng ngn protein khc nhau vn c sinh
ra trong huyt thanh mu phn ng li vi cc khng nguyn (antigens).
Chng ng vai tr bo v c th chng li s xm nhp ca cc vt l.
(v) Ngoi ra, cc protein cn l ngun dinh dng chnh cung cp
nng lng cho t bo v c th duy tr cc hot ng trao i cht v ln
ln; cc protein nh hemoglobin mang cc sinh cht theo mu i khp c
th; cc fibrinogen v fibrin c bin i t n vn c trong mu cn
thit cho qu trnh ng mu. Bn cnh , cc protein c m ch yu l
myosin phi hp vi actin to thnh actomyosin, chu trch nhim cho
hot ng co c v.v.
III. M di truyn
Gene (DNA) c cu to t bn loi nucleotide, trong khi protein
c cu to bi 20 loi amino acid. Vy vn t ra l, cc gene m
ha cho cc sn phm protein ca chng bng cch no?
Bng suy lun, ta c th suy on rng mi amino acid khng th c
xc nh bi n v m gm mt, hai hoc bn nucleotide (v 41 = 4 hoc
42 =16 th cha m ha cho 20 amino acid, trong khi 44 = 256 th li
190
d tha qu nhiu) m c l phi l mt nhm gm ba nucleotide (43 =

64). Vi 64 kiu t hp b ba ho ra l tha m ho cho 20 loi
amino acid. Nu nh th, mt amino acid c xc nh bi trung bnh ba
b ba khc nhau. Vy phi chng m di tryn l m b ba?
1. Bng chng di truyn hc v m b ba
Nm 1961, S.Brenner, F.Crick v L.Barnett phn tch chi tit nhiu
th t bin ca phage T4 nhn c bng cch x l acridin, tc nhn gy
cc t bin mt hoc thm mt cp base (chng 8), khng nh m di
truyn l m b ba (triplet code) ng nh d on. n v m (coding unit)
gm ba nucleotide xc nh mt amino acid nh vy c gi l codon.
2. Gii m di truyn
Vic tip theo l xc nh xem mi amino acid c th c m ho bi
mt hoc mt s b ba no. Cng trong nm 1961, M.Nirenberg v H.
Matthaei ln u tin s dng mRNA nhn to c thnh phn base bit
trc c tng hp bng enzyme polynucleotide phosphorylase (do
Ochoa tm ra nm 1959) v h thng tng hp l dch chit t bo E. coli
bao gm y cc yu t (cc ribosome, tRNA, amino acid, enzyme,
ATP...) cn thit cho tin hnh gii m di truyn in vitro. Vi mRNA ch
cha ton U, poly(U), chui polypeptide sinh ra ch cha ton
phenylalanine (Phe). iu chng t UUU l b ba m ho ca Phe.
Sau , Har Gobind Khorana tin hnh cc th nghim s dng cc
mRNA tng hp c cha hai, ba hoc bn nucleotide c kt ni theo
kiu lp li nh sau:
(1) Vi mRNA nhn to cha hai base l poly(UC) hay UCUCUC...,
s cha hai codon xen k UCU v CUC (ch rng s dch m in vitro
khi u ti v tr ngu nhin). Kt qu l thu c mt polypeptide gm
hai amino acid xp xen k nhau l serine v leucine, poly(Ser-Leu).
(2) Vi mRNA tng hp gm cc b ba lp li s c dch thnh cc
homopolypeptide. V d, poly(UUC) c th c c l (UUC-UUC),
hoc (UCU-UCU), hoc (CUU-CUU) ty thuc vo v tr bt u dch m.
V kt qu l c ba loi polypeptide c tng hp, poly(Phe) hoc
poly(Ser) hoc poly(Leu).
(3) Vi mRNA gm bn nucleotide lp li, v d poly(UAUC), th n
c dch thnh polypeptide cha bn amino acid lp li l poly(Tyr-LeuSer-Ile). Tuy nhin, khi s dng cc poly(GAUA) v poly(GUAA) li
khng cho kt qu. Qua so snh vi hng lot kt qu nhn c cho php
xc nh c cc codon "v ngha" hay cn gi l cc tn hiu kt thc.
T cc kt qu thu c nh vy Khorana xc nh c 'ngha' ca
191
phn ln codon c thnh phn base khng ng nht, v vic gii ton b
h thng m di truyn (genetic code) c hon thnh vo thng 6/1966.
Vi cng lao to ln Khorana v Nirenberg c trao gii thng Nobel
nm 1968. T y cho php xy dng nn bng m di truyn (Bng 6.2)
v rt ra c cc c tnh ca m nh c trnh by di y.
Bng 6.2 M di truyn (cho cc codon trn mRNA theo chiu 5'3')
3. Cc c tnh ca m di truyn
- M di truyn l m b ba (triplet code), ngha l mt b ba
nucleotide k tip m ho cho mt amino acid. Cc b ba trn gene v
mRNA gi l codon (m) v b ba c trng ca tRNA c th khp vi
codon ca mRNA theo nguyn tc b sung gi l anticodon (i m).
- M di truyn khng gi ln nhau (non-overlapping): Mi codon l mt
n v c lp, v thng tin ca mRNA c c theo mt chiu 5'3'
(hnh 6.10) bt u t codon khi u.
3'
5'
Hnh 6.10 Cc phn t tRNA mang amino acid Ser (tri) v Tyr (phi) c
m trn mRNA bng cch khp anticodon ca chng vi codon ca mRNA.
192
- M di truyn c tnh lin tc, khng b ngt qung (unpunctuated):

Ngha l khng c khong h gia cc codon.
- M di truyn c cc codon khi u (initiation) v kt thc
(termination) nm gn hai u 5' v 3' ca mRNA ng vai tr l tn hiu
khi u v kt thc tng hp chui polypeptide. Codon khi u AUG quy
nh amino acid m u chui polypeptide l methionine ( vi khun l Nformyl-methionine). Cc codon kt thc (UAA,UAG hocUGA) khng xc
nh amino acid no nn cn gi l cc codon v ngha (nonsense codon).
- M di truyn c tnh n tr, r rng (unambigous): Mi codon xc
nh mt amino acid duy nht, hoc xc nh s kt thc dch m.
- M di truyn c tnh thoi ha (degenerate): C 61 codon c ngha
(sense codon) trong khi ch c 20 loi amino acid; v vy mi amino acid
(hay tn hiu kt thc) c th c xc nh bi nhiu hn mt codon. Cc
codon cng xc nh mt amino acid nh th gi l cc codon ng ngha;
chng thng khc nhau base cui, base 3' c gi l base thoi ha.
V d, cc amino acid Arg, Ser v Leu mi ci c ti su codon ng ngha;
Ala, Gly, Pro, Thr v Val mi ci c bn codon ng ngha (xem Bng 6.2).
- M di truyn c tnh ph bin (universal), ngha l thng nht cho ton
b sinh gii.
4. Nhng ngoi l so vi m di truyn "ph bin"
Bn cnh tnh ph bin (universal) ca h thng m di truyn ni trn,
cc nghin cu gn y cho thy mt vi chch hng m hu ht l xy
ra trong cc b gene ty th (Bng 6.3). Tuy nhin, cc bo quan thc vt,
Bng 6.3 Cc ngoi l so vi m "ph bin"
Ngun
Ty th rui gim
Ty th ng vt c v
Ty th nm men
*(N = U, C, A hoc G)
Ty th thc vt bc cao
Cc nhn Protozoa
Mycoplasma
Codon
UGA
AGA & AGG
AUA
AGA & AGG
AUA
UGA
CUN*
AUA
UGA
UGA
CGG
UAA & UAG
UGA
Ngha ph bin
Kt thc
Arginine
Isoleucine
Arginine
Isoleucine
Kt thc
Leucine
Isoleucine
Kt thc
Kt thc
Arginine
Kt thc
Kt thc
Ngha mi
Tryptophan
Serine
Methionine
Kt thc
Methionine
Tryptophan
Threonine
Methionine
Tryptophan
Tryptophan
Tryptophan
Glutamine
Tryptophan
193
s bin tp RNA (RNA editing) l ph bin v khng r rng, ch: Liu

phi chng tt c cc trng hp sai lch so vi m ph bin thc vt l
cc bin i tht hay l hu qu ca s bin tp RNA trc khi dch m.
Mt vi thay i thnh thong cng xy ra cc b gene vi khun v b
gene nhn ca cc eukaryote, nhng thng th lin quan vi cc codon
kt thc. S phn b pht sinh chng loi ca cc thay i ny ch ra rng
m di truyn vn cn ang tin ha.
5. S linh hot trong vic kt cp anticodon-codon
Mc d c 61 codon c ngha nhng trn thc t trong mi t bo
prokaryote v eukaryote ch c khong 45 phn t tRNA khc nhau. Tuy
nhin, trong t bo ch c 20 loi amino acid c xc nh bi m di
truyn, nn mt s loi tRNA phi mang cng mt loi amino acid. Cc
bn sao tRNA nh th c th c trnh t anticodon ging nhau, trong
trng hp chng c th thay th chc nng cho nhau. Cc tRNA khc
th mang cc trnh t anticodon khc nhau v do vy nhn bit cc codon
khc nhau; chng c gi l isoaccepting tRNA, v giu tng i ca
chng c th nh hng ti cch thc s dng codon.
Bng 6.4 Cc nguyn tc kt cp linh hot anticodon-codon
Base 5' ca anticodon
G
C
A
U
I
Base 3' ca codon

C hoc U
G
U
A hoc G
U, C hoc A
Nm 1966, F.Crick a ra mt cch gii thch v s kt cp "lng

lo" c th xy ra v tr th ba ca cc codon ng ngha. Theo Crick,
hai base u tin ca mt codon phi c s kt cp chnh xc vi anticdon
(theo nguyn tc b sung), cn base cui ca codon th c th "linh hot"
(wobble), t c th hn so vi v tr bnh thng ca n hnh thnh nn
s kt cp base bt thng vi anticodon. ngh ny c gi l gi
thuyt linh hot (wobble hypothesis). c bit, Crick ngh rng mt
base G trong anticodon c th cp khng ch vi C v tr th ba ca mt
codon (v tr linh hot), m cn vi U. Hn na, Crick cn lu rng mt
trong s cc nucleoside bt thng c mt trong tRNA l inosine (I), vn
c cu trc tng t vi guanosine. Nucleoside ny thng thng c th
kt cp nh G, v vy ta k vng n s cp vi C (kt cp base b sung)
hoc U (kt cp base linh hot) v tr th ba ca mt codon. Nhng ng
cn lu rng inosine vn cn c th c kiu kt cp linh hot khc, by
gi ta bit l cp vi A v tr th ba ca codon. iu c ngha l,
194
mt anticodon c I v tr th nht v tim nng c th cp vi ba codon

khc nhau c base cui l C, U hoc A. Cc th nghim sau ny khng
nh iu d on ca Crick l hon ton ng v lit k cc kh nng kt
cp base linh hot nh Bng 6.4.
R rng l, hin tng kt cp linh hot ny lm gim ng k s
lng cc tRNA cn thit dch m di truyn. V d, dch m cc
codon (5'3') UUU v UUC m ho cho phenylalanine ch cn mt
tRNAPhe mang anticodon (3'5') AAG.
IV. C ch phin m v sa i sau phin m

1. Cc RNA v c im chung ca phin m
1.1. S lc v cu trc cc RNA
C bn loi ribonucleotide ni kt vi nhau bng cc lin kt
phosphodiester to thnh cc chui polynucleotide ca RNA (v nguyn tc
chung, c cp chng 5). Trong thnh phn base ca cc RNA,
ngoi bn loi c bn adenine (A), uracil (U), guanine (G) v cytosine (C),
cn pht hin mt s kiu base c sa i ph bin l trong cc tRNA
(Hnh 6.11).
Dihydrouridine
Pseudouridine
1-methyladenosine
2-thiocytidine
1-methylguanosine
5-methylcytidine
7-methylguanosine
Ribothymine
Hnh 6.11 Cu trc mt ribonucleotide Uracil c trng ca RNA (tri) v

mt s base sa i c th c trong thnh phn ca cc RNA.
C ba loi RNA c bn tham gia vo qu trnh sinh tng hp protein ca

t bo cc sinh vt, l: RNA thng tin (messenger RNA = mRNA),
RNA vn chuyn (transfer RNA = tRNA) v RNA ribosome (ribosomal
RNA = rRNA). Ring cc rRNA, prokaryote c ba loi vi cc h s lng
(sedimentation, c o bng n v Svedberg vi k hiu: S) l 5S, 16S v
23S; trong khi cc t bo eukaryote c bn loi: 5S, 5,8S, 18S v 28S.
Ngoi ra, trong cc t bo eukaryote cn c cc RNA nhn kch thc ln
v sai khc nhau gi l hnRNA (heterogenous nuclear RNA) vn l tin
195
thn ca cc mRNA, cc RNA nhn kch thc b snRNA (small nuclear

RNA) c mt trong thnh phn ca cc enzyme splicing (xem phn sau),
v cc RNA t bo cht kch thc b scRNA (small cytoplasmic RNA).
Cu trc v chc nng ca cc RNA ny s c tho lun mc V.
1.2. c im chung ca phin m prokaryote v eukaryote
Phin m (transcription) l qu trnh tng hp cc RNA khc nhau t
thng tin di truyn cha ng trong DNA. Tr cc gene m ha protein
trong cc operon vi khun, ni chung, cc RNA mi c tng hp ch l
cc bn sao s cp (primary transcript) gi l cc pre-RNA. Cc pre-RNA
ny phi tri qua mt qu trnh sa i tr thnh cc RNA trng thnh
(mature) trc khi tham gia vo qu trnh sinh tng hp protein ca t bo.
Qu trnh phin m DNA cc c im chung sau y (Hnh 6.12).
Hnh 6.12 S tng hp RNA trn mt si khun ca gene (DNA) di tc

dng ca RNA polymerase.
(i) Din ra di tc dng ca cc enzyme RNA polymerase.

(ii) Vng DNA cha gene c m xon cc b, v ch mt si n
gi l si c ngha (sense strand) c dng lm khun (template) cho
tng hp RNA.
(iii) Phn ng tng hp RNA din ra theo nguyn tc b sung v c
ko di theo chiu 5'3', ngc vi chiu ca si khun.
(iv) Nguyn liu cho tng hp l bn loi ribonucleoside triphosphate:
ATP, UTP, GTP v CTP.
(v) Sn phm ca phin m l cc RNA si n (single RNAs).
(vi) S khi u v kt thc phin m ph thuc vo cc tn hiu iu
ho l cc trnh t DNA c th nm trc v sau gene c phin m.
(vii) Qu trnh phin m c th chia lm ba bc, vn tt nh sau: M
u (initiation) l s tng tc gia RNA polymerase vi vng promoter
nhm xc nh si khun ca gene v tng hp vi nucleotide; Ko di
(elongation) l giai an sinh trng tip tc ca chui RNA dc theo si
khun cho n cui gene; v Kt thc phin m (termination) c trng
bng s gii phng si RNA v RNA polymerase ra khi khun DNA.
196
2. Cc RNA polymerase ca prokaryote v eukaryote

cc prokaryote, i din l E. coli, RNA polymerase hon chnh
(holoenzyme) l mt phc hp gm nhn t sigma () v li enzyme.
Nhn t sigma (sigma factor) gip cho RNA polymerase nhn bit v bm
cht vo promoter c th bt u phin m ti v tr chnh xc, v li
enzyme (core polymerase) ng vai tr chnh trong tng hp si RNA.
cc eukaryote, c ba loi RNA polymerase I, II v III vi s phn b
v chc nng chuyn ha khc nhau i vi b gene nhn, nh sau: RNA
polymerase I trong hch nhn (nucleolus) phin m phc hp gene
rRNA cho sn phm gm cc rRNA 18S, 28S v 5,8S; RNA polymerase
II c trong dch nhn (nucleoplasm) phin m cc gene m ha protein
cho sn phm l cc hnRNA/mRNA v c gene cho cc kiu snRNA (U1,
U2, U4 v U5); RNA polymerase III c trong dch nhn phin m cc
gene tRNA, rRNA 5S, v c snRNA U6. Ngoi ra, RNA polymerase ty
th trong ty th v chu trch nhim tng hp tt c cc RNA ca ty th.
3. Cc promoter cc prokaryote v eukaryote
(a) Cu
trc promoter
cc
Promoter
structure
in prokaryotes
5
-30
-10
Promoter
+1
prokaryote
mRNA
PuPuPuPuPuPuPuPu
AUG
transcription start site
-30 region
TTGACA
AACTGT
-10 region
TATAAT
ATATTA
-36
-12
-7
Pribnow box
-31
T T G AC A
TATA AT
82 84 79 64 53 45%
79 95 44 59 51 96%
+1
mRNA
+20
consensus
cc trnh t
iu ha
sequences
Cc nhn t phin m c th-trt DNA
(b) Cu trc promoter eukaryote

Hnh 6.13 (a) Cu trc promoter cc prokaryote. (b) Cu trc promoter
ca gene m ha protein trong nhn t bo eukaryote.
197
Cc vng khi ng (promoter) ni chung nm k trc gene v c cha

cc on trnh t c th cho php RNA polymerase nhn bit v bm cht
vo khi u phin m ti v tr chnh xc trn si khun ca gene. Vn
ny tng i phc tp cc eukaryote, v vy y ta ch xt cc
promoter ca cc gene m ha protein m khng cp cc loi promoter
ca cc gene m ha cc RNA khc. Cc promoter ca cc gene m ha
protein eukaryote v ca operon vi khun ni chung c cu trc kh tng
ng nhau. on trnh t quan trng nht ca promoter c gi l hp
TATA (TATA box) hay hp Pribnow (Pribnow box). i vi vi khun,
l trnh t TATAAT (hoc tng t nh th) nm v tr "-10'' (Hnh 6.13);
cn i vi cc gene m ha protein ca eukaryote, l trnh t TATAAA
nm gn v tr "-30" v n c trng ring cho cc RNA polymerase II.
(Cn lu l, tt c cc on tn hiu u c quy c trn si i khun
ca gene, v chng c trnh t ging nh RNA c tng hp, ch khc l
U thay cho T; cc k hiu '' v '+' ch cc v tr nm trc v sau v tr
bt u phin m, hay cn gi l cc yu t upstream v downstream).
Ngoi ra, trong cc promoter vi khun cn c trnh t TTGACA gn
v tr ''-35'', gi l on nhn bit (recognition sequence). i vi cc gene
m ha protein eukaryote, nm pha trc im bt u phin m chng 75
nucleotide c trnh t GGCCAAATCT, thng c gi l hp CCAAT
(CCAAT box) - c l "hp cat"; n ng vai tr iu ha tc phin m.
Ni chung, cc vng ny c bo tn cao v c th cho tng loi
RNA polymerase nht nh, c gi l cc trnh t iu ha (consensus
sequences). Cc t bin thay th base ti cc hp TATA, ngha l lm cho
n bt ging vi trnh t c bo tn (v d, TATAAT TGTAAT) do
s lm yu kh nng phin m ca promoter, gi l down mutation.
Ngc li, cc t bin lm cho cc trnh t promoter tr nn ging vi cc
trnh t iu ha (v d, TATCTT TATAAT), s lm mnh kh nng
phin m ca promoter, gi l up mutation.
4. Cc giai on ca qu trnh phin m
y ch cp mt m hnh n gin v qu trnh phin m E. coli.
- Giai on bm v khi u: Sau khi RNA polymerase holoenzyme
nhn bit v bm cht vo promoter, lm tho xon mt on chng 12 cp
base ti y. Sau khi tng hp c mt vi nucleotide, nhn t sigma tch
ra i vo mt chu k phin m khc, gi l chu k sigma (sigma cycle).
- Giai on ko di: Enzyme li tin hnh ko di si RNA dc theo
si khun. RNA polymerase li tin n u th DNA c m xon v
phin m n y; v vng DNA c phin m ng xon tr li.
198
- Giai on kt thc: Khi qu trnh phin m tng hp xong hai on kt

thc giu GC v AT nm ng sau gene th ti vng ui si RNA hnh
thnh cu trc ''nt ci tc'' lm dng s phin m ca li RNA polymerase.
Sau , di tc dng ca nhn t rho () c bn cht protein, si RNA va
c tng hp v enzyme li c gii phng ra khi DNA khun.
5. S sa i sau phin m i vi cc mRNA eukaryote
Nh cp, tr mRNA prokaryote ra, tt c cc RNA cn li d
pro- hay eukaryote u phi tri qua qu trnh sa i sau phin m vi rt
nhiu c ch tinh vi v phc tp khc nhau to ra cc RNA trng thnh
tham gia vo qu trnh dch m; eukaryote, cc qu trnh ny xy ra trong
nhn. c ci nhn h thng, y ta hy tm hiu mt t v cc c ch
hon thin cc bn sao s cp mRNA (pre-mRNA) cc t bo eukaryote.
5.1. Gn thm "m" m7Gppp v "ui" poly(A)
tr thnh phn t mRNA trng thnh trc khi i ra t bo cht
lm khun cho dch m, tt c cc pre-mRNA ca cc gene m ha protein
khc nhau t bo eukaryote, u c lp thm ci "chp" 7methylguanosinetriphosphate (m7Gppp cap) vo u 5' v "ui" poly(A)
vo u 3' (Hnh 6.14). i vi cc gene m ha protein c vng m ha l
lin tc (khng b gin on bi cc exon) nh cc gene histone chng hn,
qu trnh hon thin mRNA dng li y. Loi ny chim khong 10%.
chp 5'm7Gppp
Trnh t m ho
sau khi loi b
cc intron
ui poly(A)
Hnh 6.14 Cu trc in hnh ca mt mRNA trng thnh eukaryote.
Cn lu rng, u 3' ca hu ht cc gene m ha protein eukaryote

c cha trnh t AATAAA ng vai tr l tn hiu cho vic gn "ui"
poly(A) vo u 3' ca mRNA. S phin m thng thng vn cn tip din
sau khi i qua v tr polyadenyl ho ny. Trnh t tng ng vng cui 3'
mRNA c phin m l AAUAAA bo hiu cho endonuclease nhn bit
v ct chui RNA ti mt im xc nh nm sau n khong 10-30 base.
Sau , mt enzyme khc l poly(A)-polymerase s lp thm vo u 3' ca
mRNA mt dy adenine di khong 150-200 base gi l ui poly -A (poly
[A] tail; Hnh 6.14). ui poly(A) c chc nng bo v mRNA khi b suy
thoi v trong nhiu trng hp n cn kch thch s dch m.
5.2. S ct-ni i vi pre-mRNA ca cc gene phn an (split gene)
V d, gene ovalbumin gm by intron xen k gia tm exon c di
7.700 cp base c E.Chambon phn tch trnh t nm 1981. Sau khi
199
enzyme splicing ct b cc intron v ni tt c cc exon trong mt qu

trnh gi l x l RNA (RNA processing) th mRNA trng thnh c vng
m ha protein di 1.872 base (Hnh 6.15).
Gene
ovalbumin
phin m
Bn sao RNA
s cp
1. lp chp 5'
2. lp ui poly(A)
Chp 5'm7Gppp
ui poly(A)
loi b 5 intron (splicing)
mRNA trng thnh
loi b 2 intron (splicing)

xut ra t bo cht
Hnh 6.15 Phin m gene ovalbumin v s to thnh mRNA trng thnh.
Vic l gii c ch ct-ni (splicing) trong qu trnh x l pre-mRNA

da ch yu trn hai s kin sau: (i) hai u mt ca mi intron c hai
nucleotide rt n nh, gi l cc "trnh t chun", l 5'-GU......AG-3'.
Mi intron ni chung c di khong 102-104 nucleotide; v (2) mt
s snRNA cha trong thnh phn ca enzyme splicing cng c cc trnh t
dinucleotide b sung vi cc trnh t chun trong intron. snRNA trong
phc hp snRNP (small nuclear ribonucleoprotein) tng tc vi cc u
mt ca mi intron, ko hai u mt xch li gn nhau to ra cu trc hnh
vng, nh enzyme tin hnh ct b intron v ni cc exon li vi nhau.
mRNA
tin thn
intron b ct b
(thng lng)
ct pha
5'exon
ct pha 3'exon
v splicing
imct 5'
im ct 3'
ni cc u 5' v
3' ca cc exon
mRNA
trng thnh
Hnh 6.16 Mt m hnh v c ch ct-ni trong qu trnh x l pre-mRNA.
Vn t ra l s c mt cu cc intron trong cc gene phn on

nh th c ngha g? Bi v vi li t chc nh vy lm cho trnh t m
200
ho ca gene b gin an, v trong qu trnh ch bin pre-mRNA ca n

c th xy ra d l mt sai st nh cng to ra mRNA c khung c
m b thay i. Ngi ta cho rng c khong 90% bn sao mRNA b suy
thoi v ch li khong 10% mRNA trng thnh i ra t bo cht.
Theo quan nim hin nay, s c mt ca cc intron trong cc gene
phn on c th c cc vai tr sau: (i) cc intron nh l cc on m
(spacer) to thun li cho s ti t hp gia cc exon bn trong gene; (ii)
cc intron nh l cc vng m tch bit cc vng chc nng ca mt s
protein; v (iii) cc intron nh l cc vng phn cch cho php cc exon
c th c ct-ni c chn lc (alternative splicing) to ra cc mRNA
trng thnh khc nhau v dch m thnh cc polypeptide khc nhau t
mt gene; nh ni trc y, con ng ct-ni ny mang tnh c th
cho tng m cc eukaryote bc cao.
V. Cu trc v chc nng ca cc loi RNA v ribosome

1. RNA thng tin (messenger RNA = mRNA)
Cc mRNA l loi RNA quan trng nht
dng lm khun cho tng hp polypeptide
(Hnh 6.17); chng c cu trc 'm' vi kch
thc khc nhau ty tng gene v u c ba
phn chnh nh sau (xem thm Hnh 6.14):
5'-UTR
vng m ha 3'-UTR
(i) Vng dn u (5'UTR) tuy khng c

dch m nhng cn thit cho s bm vo ca
tiu n v ribosome b.
(ii) Vng m ho (coding region) nm k
sau 5'UTR, mang thng tin cu trc ca mt
polypeptide, nu l mRNA ca eukaryote hoc
Hnh 6.17 Mt on ca phn t mRNA vi trnh t cc codon ca n.
mang thng tin ca nhiu polypeptide khc nhau (cch nhau bi cc on

m khng c dch m), nu l mRNA ca prokaryote.
(iii) Vng theo sau (3'-UTR) nm cui gene, khng c dch m.
2. RNA vn chuyn (transfer RNA = tRNA)
Cc tRNA c chc nng chnh l mang amino acid v dch m cho mt
codon trn mRNA (Hnh 6.10 v 6.18). Trong thnh phn ca chng
thng c mt s base him tp trung cc vng thn (stem loop) nh:
dihydro-uridine (DHU), inosine (I), ribothymidine (T) v pseudouridine
201
() (xem hnh 6.11). Cc tRNA u c cu trc khng gian ba chiu gn

chc l do s kt cp cc base c th mt s on ca chng (Hnh
6.18). Ni chung, cc phn t tRNA gm khong 75-85 base, vi h s
lng chng 4S; chng thng rt ging nhau nhiu on v sai khc ch
yu l anticodon. Mi tRNA thng c 3-4 vng vi chc nng khc
nhau: (i) vng DHU nhn bit aminoaxyl-tRNA synthetase; (ii) vng
anticodon c m trn mRNA bng s kt cp anticodon-codon; (iii) vng
"ph" (extra loop) c th khng c mt s tRNA; (iv) vng TC nhn
bit ribosome i vo ng v tr tip nhn aminoaxyl-tRNA (v tr A);
v (v) on mch thng CCA(3') l v tr nh ca amino acid.
V tr nh
amino acid
Lin kt hydro
gia cc cp base
Anticodon
Hnh 6.18 Cu trc bc ba (tri) v bc hai ca mt phn t tRNA.
3. RNA ribosome (ribosomal RNA = rRNA)

Cc rRNA cng vi cc protein c th l nhng thnh phn cu trc
nn cc ribosome -"nh my" tng hp protein ca t bo (Hnh 6.19).
vi khun c 3 loi rRNA c cc h s lng l 23S, 16S v 5S, vi s lng
nucleotide tng ng l 2904, 1542 v 120. t bo eukaryote c 4 loi
rRNA vi cc h s lng l 28S, 18S, 5,8S v 5S.
4. Ribosome
Tiu n v b
R 30S/40S
R 50S/60S
ng knh
R 70S vi khun
rRNA: 16S
Protein: 21 phn t
rRNA: 23S + 5S
Protein: 34 phn t
18-20 nm
R 80S eukaryote
rRNA: 18S
Protein: >30 phn t
rRNA: 28S +5S +5,8S
Protein: >50 phn t
20-22 nm
Tv ln
Hnh 6.19 S cu trc mt ribosome vi hai tiu n v ln v b.
Mi ribosome c hai tiu n v b v ln (small and large subunits).
202
Tiu n v b c chc nng bm vo mRNA trc tin trong dch m.

Tiu n v ln c cha peptidyl transferase xc tc hnh thnh cc lin
kt peptide; n c cha hai v tr: v tr A l ni bm vo ca aminoacyltRNA v v tr P l ch dng tm ca peptidyl-tRNA. Hai tiu n v ny
ch kt hp vi nhau to ra mt ribosome hot ng khi qu trnh dch
m trn mRNA thc s bt u.
VI. C ch dch m (translation)

Dch m (translation) hay
tng hp protein l mt qu
trnh sinh hc quan trng din
ra trong t bo cht, v ph
thuc vo nhiu yu t; quan
trng nht l mRNA, cc tRNA
v ribosome. mRNA mang
thng tin quy nh trnh t kt
hp cc amino acid vo chui
polypeptide, m vic dch m
mRNA c thc hin bi cc
aminoacyl-tRNA, cn ribosome
ng vai tr n nh vic kt
hp gia mRNA vi cc tRNA
(Hnh 6.20). Qu trnh ny c
chia lm hai giai on di y.
DICH MA
PROTEIN
Hnh 6.20 i cng v cc qu trnh phin m v sa i sau phin m

din ra trong nhn, v dch m trong t bo cht t bo eukaryote.
1. Hot ho amino acid

Qu trnh ny din ra trong bo tng v to ngun cc tRNA mang
cc amino acid sn sng tham gia dch m. Mi amino acid c nh vo
tRNA thch hp nh mt enzyme aminoacyl-tRNA synthetase c th.
Trc tin, enzyme ny (E) xc tc cho phn ng ATP hot ho amino
acid, vi s c mt ca Mg2+, to ra phc hp [Eaminoacyl~AMP].
RCH(NH2)COOH + ATP E*[RCH(NH2)CO~AMP] + PiP
Tip theo, cng di tc dng ca enzyme , phc hp ny kt hp
vi tRNA thch hp bng lin kt ng ho tr to ra aminoacyl-tRNA.
E*[RCH(NH2)CO~AMP] + tRNA RCH(NH2)CO~tRNA + AMP
2. C ch ca qu trnh dch m (tng hp polypeptide)
Bc 1: M u (initiation)
203
Qu trnh dch m bt u khi mt tiu n v ribosome b bm vo

mRNA ti v tr ca codon khi u AUG. Lc ny mt phn t tRNA
khi u c th mang methionine ( vi khun l formyl-Met) i vo v
khp anticodon ca n vi codon m u ca mRNA. K , tiu n v
ribosome ln bm vo tiu n v b to ra mt ribosome hot ng hon
chnh. Lc ny Met-tRNA v tr P v v tr A trng; mt tRNA th hai
(v d, tRNAVal) i vo v tr A v khp vi codon th hai (hnh 6.21A).
A
Lin kt peptid
Tch v gii phng
D
Chui gm 8
amino acid
Nhn t RF
Hnh 6.21 Qu trnh sinh tng hp chui polypeptide.
Bc 2: Ko di (elongation)
Qu trnh ko di bt u sau khi lin kt peptide u tin c hnh
thnh. Phn ng ny c xc tc bi enzyme peptidyl transferase, v kt
qu l to ra mt peptidyl-tRNA v tr A (hnh 6.21B). Sau , ribosome
lp tc chuyn dch sang mt codon mi dc theo mRNA theo chiu
204
5'3' (hnh 6.21C). Phn ng ny y phn t tRNA t do vn v tr P

ra ngoi; lc ny peptidyl-tRNA nm v tr P v v tr A li trng. Mt
chu k dch m mi li bt u, mt aminoacyl-tRNA th ba i vo v
khp anticodon ca n vi codon ang trng v tr A, mt lin kt
peptid th hai c hnh thnh, v ribosome li dch chuyn sang codon
k tip. Qu trnh ni trn c din ra mt cch tun t dc theo mRNA
lm cho chui polypeptide di dn ra cho n dch m xong codon 'c
ngha' cui cng.
Bc 3: Kt thc (termination)
Nhn t RF
Qu trnh tng hp chui

polypeptide s dng li khi mt
codon kt thc c a i din
vi v tr A trng, vn c
nhn bit bi mt protein kt thc
gi l nhn t gii phng RF
(release factor). S c mt ca n
Protein mi tng hp
Hnh 6.22 S kt thc dch m.
cng vi enzyme transferase ct ri chui polypeptide ra khi tRNA cui

cng (hnh 6.21D) v phng thch hai tiu n v ribosome cng nh
chui polypeptide v tRNA ra khi mRNA (hnh 6.22).
Hnh 6.23 So snh cc c ch tng hp v dch m mRNA cc t bo

eukaryote (tri) v prokaryote.
205
Mt s im cn lu thm:
(1) Trn y mi ch phn tch hot ng ca mt ribosome trn
mRNA. Thc ra, trn mt mRNA c rt nhiu ribosome cng hot ng,
gi l polyribosome hay polysome, to ra nhiu polypeptide ging nhau.
(2) Trn nguyn tc, amino acid m u s c ct b khi chui
polypeptide (sau khi tng hp c vi amino acid nh trong trng hp
cc vi khun) hoc trc khi chui c tng hp y (nh trng
hp eukaryote). Tuy nhin, cc eukaryote khng phi lc no amino acid
m u ny cng b tch b, m trong mt s protein n vn c gi li.
(3) Sau khi c tng hp, cc chui polypeptide s cp ny s c
sa i v chuyn sang cc bc cu trc cao hn theo cch c th tr
thnh cc protein hot ng chc nng (xem cc hnh 6.8 v 6.9).
(4) Tham gia vo cc bc m u, ko di v kt thc cn c cc yu
t protein, vi tn gi tng ng l cc nhn t m u (IF: initiation
factor), nhn t ko di (EF: elongation factor), v nhn t gii phng
(release factor) cng vi ATP, GTP v cc ion nh Mg2+, K+ v NH+4.
(5) Trong cc t bo prokaryote, do khng c mng nhn v cc
mRNA a cistron vn d khng phi qua sa i sau phin m, cho nn
cc ribosome v cc aminoacyl-tRNA s bm vo u 5' ca mRNA
bt u qu trnh dch m ngay trong khi u 3' ca n qu trnh phin
m ang cn tip din. Ngc li, cc t bo eukaryote v c mng nhn
phn cch v cc pre-mRNA cn phi tri qua cc cng on sa i phc
tp sau phin m (tt c u din ra trong nhn), cn dch m din ra sau
trong t bo cht (hnh 6.23). V th cho nn phin m v dch m r
rng l hai qu trnh tch bit nhau c v c khng gian ln thi gian.
Cu hi v Bi tp
1. Ti sao ni gene l khi nim cn bn ca di truyn hc v tht kh
c th a ra mt nh ngha chnh xc? Hy chng minh iu qua
cc giai on pht trin ca di truyn hc cho n nay.
2. Bn hiu g v cc gene phn on (split gene)? Cho th d v s
minh ho. Cc intron l g v c vai tr nh th no? Phn tch mt trng
hp sa i (sau phin m) sn phm ca gene phn on lm sng t
mnh mt gene c th xc nh nhiu hn mt loi polypeptide.
3. (a) Hy lm sng t nhn nh sau: Khc vi cc t bo prokaryote,
s phin m v dch m cc t bo eukaryote l hai qu trnh tch bit c
v khng gian ln thi gian. (b) Qu trnh tng hp v hon thin cc
206
RNA prokaryote v eukaryote ging v khc nhau nhng im no?

4. Trnh by vai tr chnh ca cc yu t tham gia vo qu trnh sinh
tng hp protein ca t bo v phn tch c ch sinh tng hp protein da
trn s tng tc gia mRNA, cc aminoacyl~tRNA v ribosome.
5. Bng suy lun, hy cho bit ti sao mt m di truyn ch c th c
m ha theo nguyn tc b ba m khng th l kiu khc? Bng thc
nghim iu c gii quyt nh th no? Tnh thoi ha ca m v
nguyn tc kt cp linh hot c quan h vi nhau ra sao? Cho v d.
6. Phn tch s ph hp gia cu trc v chc nng ca cc loi RNA
v mi quan h gia gene v protein.
7. Gi s tng hp c mt mRNA c thnh phn 75%U v 25%G.
Khi s dng mRNA ny tng hp protein in vitro thu c cc
amino acid trong cc protein vi cc tn s nh sau :
Phe : Val : Leu : Cys : Gly : Trp = 1,00 : 0,44 : 0,33 : 0,33 : 0,15 : 0,11.
Hy trnh by phng php v ch ra kt qu ca vic gii on cc
codon cho mi amino acid ni trn (khng s dng bng m di truyn).
Bit rng cc codon cng xc nh mt amino acid thng c hai
nucleotide u ging nhau, v Cys c xc nh bi UGU.
8. (a) Hm lng GC ca DNA phage T3 l 53%. Bn s k vng hm
lng G+C ca mRNA T3 ra sao? (b) Nu bit c hm lng purine
ca DNA phage T3 v khng bit mch no lm khun, c th d on
hm lng purine ca mRNA T3 hay khng? Ti sao, hoc ti sao khng?
9. Nu s dng cc phn t mRNA nhn to c thnh phn gm cc
cm gm ba hoc bn nucleotide lp li di y tin hnh tng hp
protein trong ng nghim, thnh phn amino acid thu c t cc
polypeptide s nh th no? C trng hp no khng tng hp c
protein hay khng? Ti sao?
(a) (UUC)n ; (b) (UAC)n ; (c) (GAUA)n ; (d) (GUAA)n.
10. Nu s dng ba phn t mRNA tng hp c thnh phn gm cc
base c kt hp ngu nhin theo t l sau y tin hnh tng hp
protein in vitro, th thnh phn v t l cc amino acid c kt hp trong
cc protein s nh th no? (a) 1U:5C (b) 1A:1C:4U (c) 1A:1C
Ti liu Tham kho

Ting Vit
207

Ting Anh
Alberts B, Johnson A, Lewis J, Raff M, Robert K, Walter P. 2002.
Molecular Biology of the Cell. Garland Science, NY.
Cambridge Healthtech Institut. 2005. Gene Definition.
www.healthtech.com
Cooper DN. 2004. Gene structure, function and expression. http://www.
cardiff.ac.uk/medicine/medical_genetics/study/medical_teaching/
McClean P. 1998. Definition of Gene.
http://www.ag.ndsu.nodak.edu/plantsci/undrcour.htm
Lewin B. 1999. Genes VI. Oxford University Press, Oxford.
Palladino MA. 2002. Understanding the Human Genome Project.
Benjamin/Cummings Publishing Company, Inc., Menlo Park, CA.
Cambridge Healthtech Institut. 2005. RNA Glossary.
www.healthtech.com
Company, Inc., Menlo Park, CA.
Tamarin RH. 1999. Principles of Genetics. 6th ed., McGraw-Hill, Inc, NY.
Twyman RM. 1998. Advanced Molecular Biology. BIOS Scientific
Publishers Ltd/ Springer-Verlag Singapore Pte Ltd.
Molecular Biology of the Gene. 4th ed., Benjamin/Cummings Publishing
Companies, Inc./ Wm.C.Browm Publishers, Dubuque, IA.
Mt s trang web b sung
Gene structure, function and expression.
http://www.cardiff.ac.uk/medicine/medical_genetics
http://www.oup-usa.org/isbn/019879276X.html
208
Chng 7
S iu ha Biu hin ca Gene

I. Cc nguyn l iu ha v mc kim sot phin m
Khng phi tt c cc gene u c biu hin lin tc. Mc biu
hin ca gene khc nhau gia cc t bo hoc khc nhau theo giai on
trong chu trnh t bo. Chng hn gene m ha cho hemoglobin c biu
hin mc cao ch trong t bo tin th (precursor) ca t bo mu.
Hot tnh ca gene khc nhau theo chc nng t bo. ng vt c xng
sng nh chut, cha khong 200 loi t bo c phn ha chc nng
khc nhau. Tt c cc t bo u cha cng thng tin di truyn, nhng t
bo khc nhau ch nhng gene hot ng. Trong nhiu trng hp, hot
tnh ca gene c iu ha mc phin m, c qua nhng tn hiu bt
u bn trong t bo v c phn ng vi nhng iu kin bn ngoi. Tuy
nhin thng tin di truyn c iu ha theo nhng cch khc nhau. Cc
bc iu khin hot ng gene bao gm:
- Cu trc li DNA, trong nhng thay i biu hin gene ph
thuc vo v tr trnh t DNA trong genome.
- iu ha phin m trong tng hp bn phin m RNA bng s iu
khin s m u v s kt thc
- Qu trnh ch bin RNA hoc iu ha qua qu trnh ct-ni trn
RNA (RNA splicing)
- iu ha dch m qu trnh tng hp chui polypeptid
- S bn vng ca mRNA
C s khc nhau ng k trong s iu ha biu hin ca cc gene
eukaryote v prokaryote. Prokaryote l nhng c th n bo sng t do,
sinh trng v phn chia trong iu kin thch hp v c cung cp y
cht dinh dng. Do hot ng ca cc gene c iu ha do nhu
cu ca t bo khi cn thit.
Khc vi prokaryote, eukaryote l nhng c th a bo. Trong c th
ang pht trin, mt t bo khng ch sinh trng v phn chia m t bo
th h sau tri qua nhng thay i quan trng v hnh thi v ha sinh v
duy tr trng thi bin i ca n. Hn na trong qu trnh pht trin phi,
t bo eukaryote t chu nh hng ca mi trng hn so vi vi khun.
Cui cng, c th trng thnh, s sinh trng v phn chia t bo ca
hu ht cc loi t bo b ngng, mi t bo ch phi duy tr cc tnh cht
ring bit ca n.
209
A. iu ha m tnh
im bm
ca repressor
Phin m
Khng phin m
Protein repressor
bm vo
B. iu ha dng tnh
im bm ca
nhn t hot ha
Khng phin m
Phin m
Protein hot ha phin m
bm vo
Hnh 7.1 M hnh iu ha m tnh (negative regulation) v iu ha

dng tnh (positive regulation).
A. Trong iu ha m tnh, protein c ch bm vo phn t DNA, ngn cn
phin m
B. Trong iu ha dng tnh, s bm vo ca protein hot ha phin m, kch
thch phin m.
II. iu ha hot ng gene prokaryote

vi khun v phage, hot tnh ng m gene thng c iu khin
qua phin m tng hp cc mRNA xy ra khi sn phm ca gene c cn
n.
C ch phn t cho mi m hnh iu ha hon ton khc nhau,
nhng thng theo mt trong hai kiu chnh: iu ha m tnh v iu ha
210
dng tnh (Hnh 7.1). Trong h thng iu ha m tnh (Hnh 7.1A) mt

protein c ch c mt trong t bo, ngn cn s phin m. Trong h thng
cm ng c iu ha m tnh, protein c ch hot ng lm ngn cn
phin m. Nhn t cm ng km hm cht c ch, cho php bt u phin
m. Trong h thng c ch, protein aporepressor gn vi co-repressor to
ra cht c ch c hot tnh, lm ngn cn phin m. Ngc li trong h
thng iu ha dng tnh (Hnh 7.1B), s tng hp mRNA xy ra nu
protein iu ha gn vo mt vng ca gene lm hot ha phin m.
Nhng protein ny c xem l nhng nhn t hot ha phin m. iu
ha m tnh v dng tnh khng loi tr ln nhau. Mt vi h thng l c
iu ha m tnh v dng tnh, s dng c 2 h thng iu ha phn
ng vi cc iu kin khc nhau trong t bo. iu ha m tnh l ph
bin cho prokaryote, trong khi iu ha dng tnh li ph bin cho
eukaryote.
1. Cu trc ca operon
M hnh operon ca iu ha phin m
C ch iu ha di truyn ca h thng lac (lac system) c gii
thch bng m hnh operon ca Francois Jacob v Jacque Monod (1960)
(Hnh 7.2).
H thng s dng lactose gm 2 loi thnh phn: gene cu trc m
ha protein cn thit cho s vn chuyn v chuyn ha lactose v cc yu
t iu ha (gene c ch lacI, promotor lac P v operator lacO).
Sn phm gene cu trc c m ha bi mt phn t mRNA a
cistron (polycistronic). Gene Z m ha cho enzyme - galactosidase (thy
phn ng lactose thnh galactose v glucose), gene Y m ha cho
enzyme permease (cn cho vn chuyn lactose qua mng), gene A m ha
cho enzyme transacetylase (vai tr chuyn ha lactose cha r).
t bin promotor (lacP-) lm mt kh nng tng hp mRNA.
Sn phm ca gene lacI l cht c ch, n bm vo trnh t cc base
ca DNA cu to operator. Cht c ch bm vo operator, ngn cn s
khi u phin m mRNA nh RNA polymerase. Cht cm ng (lactose)
kch thch s sinh tng hp mRNA bng cch kt hp v lm bt hot cht
c ch. S c mt ca cht cm ng lm cht c ch khng gn vo
operator, promotor cho php khi u tng hp mRNA.
Khi mi trng c lactose, lactose c chuyn vo t bo nh
permease. Khi vo trong t bo mt s lactose (lin kt -1,4) c
chuyn thnh allolactose (lin kt -1,6) nh -galactosidase. Allolactose
l cht cm ng, n gn vo protein km hm, gy bin i cu hnh to
211
phc hp allolactose-repressor. Phc hp ny mt kh nng gn vo

operator. Lc ny operon m ra, RNA polymerase bt u phin m t
gene cu trc. Cc yu t iu ho
Nhm gene cu trc
[A]
Trc tip phin m
[B]
Repressor gn vo operator,
ngn cn phin m
mARN
Repress
or
protein
[C]
Phc hp cht cm ng-cht c
ch khng th gn vo operator
Inducer
Khi khng lactose, RNA polymerase bt
u phin m tng hp protein z, y v a
Lac mARN
galactosidase
Permeas
e
Transacety
lase
Hnh 7.2 A Bn ca operon lac;

B. S ca operon lac trng thi b km hm
C. S ca operon lac trng thi c kch thch
Khi mi trng khng c lactose, protein c ch c hot tnh gn vo

operator, lm s phin m ca tt c cc gene cu trc ca operon lac b
dng.
S iu ha ca operon yu cu promotor nm chng ln mt phn
hoc k st bn promotor ca gene cu trc, v n gn vi cht c ch
212
ngn cn phin m.
2. iu ha dng tnh operon lactose
Chc nng ca -galactosidase trong chuyn ha lactose to ra
glucose bng cch ct lactose (mt sn phm ct khc l galactose cng c
th c chuyn thnh glucose nh enzyme ca operon galactose). Nu c
glucose v lactose c mt trong mi trng sinh trng, khng cn hot
ng ca operon lac. Trong mi trng c glucose, enzyme galactosidase khng c to thnh cho n khi glucose trong mi trng
c s sng ht. S c mt ca glucose lm mRNA khng c tng
hp, do khng c s tng hp -galactosidase, v s thm vo nhn t
cm ng lm bt hot cht km hm. Mt yu t khc cn cho s bt u
tng hp mRNA, hot tnh ca yu t ny c iu ha bi nng
glucose.
Glucose c nh hng c ch gin tip ln s biu hin ca operon
lac. Nhng phn t nh adenosine monophosphate vng (cAMP) phn b
rng ri trong m ng vt v trong cc c th eukaryote a bo, c vai tr
quan trng lm cht trung gian hot ng hormone. Cht ny cng c
trong t bo E. coli v nhiu t bo vi khun khc vi chc nng khc
nhau. cAMP c tng hp bi enzyme adenyl cyclase, v nng ca
cAMP c iu ha gin tip qua trao i cht glucose. Khi vi khun
sinh trng mi trng cha glucose, hm lng cAMP rt thp. Trong
mi trng cha glycerol hoc cc ngun carbon khng th i vo con
ng ha sinh c s dng trao i cht glucose (con ng
glycolytic) hoc khi vi khun b i ngun nng lng, nng cAMP
cao. Hm lng glucose gip iu ha nng cAMP trong t bo v
cAMP li iu ha hot tnh ca operon
lac.
E. coli cha protein nhn cAMP
hay CRP (cyclic AMP receptor protein)
cn c gi l protein hot ha d ha
CAP (catabolite activator protein), c
m ha bi gene crp. t bin gene
crp v gene adenyl cyclase lm ngn
cn s tng hp ca mRNA lac. iu
ny cho thy chc nng ca CRP v
cAMP cn thit cho tng hp mRNA Hnh 7.3 Cu trc ca cAMP
lac. CRP v cAMP gn vo mt v tr khc to phc hp cAMP-CRP c
biu hin. Phc hp ny l mt yu t iu ha hot ha h thng lac.
213
Tng hp ca mRNA
l
khng
Repressor
khng
Phc hp
cAMP-CRP
C
Phin m
khng
Hnh 7.4 Bn trng thi iu ha ca operon lac
Nhu cu v cAMP-CRP ph thuc vo h thng c ch lac, v t

bin crp v adenyl cyclase khng th to mRNA lac ngay c khi c mt
t bin gene iu ha (lacI-) v gene ch huy (lacO-). S d nh vy l
v phc hp cAMP-CRP phi gn vo trnh t base trn DNA vng
promotor xy ra phin m (Hnh 7.4). Khc vi cht c ch trong iu
ha m tnh, phc hp cAMP-CRP l cht iu ha dng tnh. Cc th
nghim iu kin in vitro cho thy: mRNA lac c tng hp ch khi c
cAMP vng v khng c cht c ch.
Khi vng mt phc hp cAMP-CRP, RNA polymerase ch bm lng
lo vo promotor. V vy him khi dn n phin m v khng c s tng
tc ng gia RNA polymerase v promotor. Nhng RNA polymerase
c kch thch gn vo promotor khi cAMP-CRP c gn vo DNA.
Nhng kt qu ny gii thch chc nng lactose v glucose cng nhau
tham gia iu ha phin m operon lac nh th no.
3. iu ha m tnh operon tryptophan
Operon tryptophan (trp) ca E.coli cha cc gene cu trc m ha
cho cc enzyme tng hp amino acid tryptophan. Operon ny c iu
ha theo cch sau: khi tryptophan c mt y trong mi trng sinh
trng, s phin m ca operon b c ch. Khi s cung cp tryptophan b
thiu, s phin m xy ra. S iu ha ca operon lactose tng t vi
214
operon lactose, v s tng hp mRNA c iu ha m tnh nh cht c

ch. Tuy nhin, khc vi iu ha operon lac, tryptophan hot ng nh
cht ng km hm, kch thch cht c ch gn vo operator ngng s tng
hp. Operon tryptophan hot ng theo kiu c ch, iu ha m tnh.
Tryptophan c tng hp qua cc giai on kh phc tp, mi giai
on c s xc tc ca mt enzyme c bit. Cc gene m ha cho cc
enzyme ny nm k nhau trn nhim sc th ca E.coli. l cc gene
trpE, trpD, trpC, trpB, trpA. Cc enzyme c dch m t mt phn t
mRNA a cistron. Vng m ha gene E c dch m trc tin. Pha
trc trpE v u 5' c promotor, operator v 2 vng xp ln lt l leader
(trpL) v on km hm phin m attenuator (trpa, khng phi l trpA).
Gene c ch trpR nm xa operon, tng hp protein aporepressor, l cht
km hm m ring n khng c hot tnh. Khi tryptophan d tha, n kt
hp vi aporepressor to cht km hm c hot tnh, gn vo operator ca
operon tryptophan lm dng phin m cc gene cu trc. Khi nng
tryptophan thp, n tch khi phc hp km hm v aporepressor mt hot
tnh. Lc ny operator m ra, RNA polymerase dch m 5 gene cu trc
tng hp 5 enzyme tham gia tng hp ra tryptophan. (Hnh 7.5).
Phin m xy ra
trp P trp O trp L
trp E
trp D
trp C
Phin m
Aporepressor
Aporepressor khng
bm vo operator
Phin m b c ch
trp P
trp O
trp L
trp E
trp D
trp C
Khng phin m
Phc hp Tryptophanaporepressor bm vo
operator v c ch phin m
Tryptophan
Hot ha aporepressor
Hnh 7.5 iu ha ca trp operon E. coli

A. Protein aporepressor khng bm c vo operator, phin m xy ra.
215
B. Khi c tryptophan, phc hp aporepressor v tryptophan lm cht c ch

hot ng gn c vo operator, s phin m b km hm.
4. Phin m d (Attenuation)
Kiu iu ha th hai c pht hin operon tryptophan c gi l
attenuation. N dng s dch m iu khin s phin m. Khi c mt
tryptophan ni bo, ngay c vi nng thp, s dch m mt phn vng
leader ca mRNA ngay khi va c tng hp, kt qu lm dng s phin
m trc khi gene cu trc u tin ca operon c sao chp.
[A
]
[B
]
Kt
thuc
phin
ma
Hnh 7.6 (A) S phin m ca leader trp;

(B) Chi tit cu trc ca 2 codon trp vng 1-2
Phin m d (attenuation) l kt qu s tng tc gia cc trnh t

DNA trong vng leader ca bn phin m trp. t bo kiu di, s phin
m operon trp thng c bt u. Tuy nhin khi c mt mt lng nh
tryptophan, hu ht phn t mRNA kt thc vng 28 base c bit
trong trnh t leader. Kt qu ca s kt thc sm ny to phn t mRNA
cha 140 nucleotide chm dt mt on ngn ca cc gene m ha cho
cc enzyme trp. Vng 28 base xy ra s kt thc phin m sm nh th
c gi l attenuator. Trnh t base ca vng ny thng c cc tnh cht
im kt thc, gm dng on v vng (stem-loop) trn mRNA theo sau l
trnh t ca 8 uridine.
Trnh t leader c cc c im:
216
- Mt vng c codon AUG v pha sau l codon kt thc UGA, m

ha cho mt polypeptide cha 14 amino acid c gi l leader
polypeptide.
- Hai codon tryptophan v tr 10 v 11 trn mRNA ca leader
polypeptide. Trnh t lp li ngn ny c ngha trng iu ha.
- Bn on ca RNA leader l vng 1, 2, 3 v 4 to thnh do kh
nng kt cp ca cc base vi nhau. Cc base vng 1 kt cp vi vng 2,
vng 3 kt cp vi vng 4 (Hnh 7.6).
Khi s kt cp xy ra dng ny, s phin m kt thc on i qua
uridine pha trc nucleotide 140. Kiu kt cp ny xy ra mRNA leader
c tinh sch.
- Mt kiu kt cp bin i c th xy ra, trong cc base vng 2 kt cp
vi vng 3 nh cc cp base 2 vng ny gn nh b sung nhau (Hnh
7.6B). Qua m hnh kt cp base bin i ny (3-4 hoc 2-3), s t chc
trnh t mRNA c th iu ha phin m qua dch m ca leader
polypeptide (Hnh 7.7). Khi vng leader c phin m, s dch m leader
polypeptid cng bt u. V c 2 codon ca tryptophan trong trnh t m
ha, nn s dch m nhy cm vi s lng tRNAtrp a vo.
Nu mi trng cung cp y tryptophan, ribosome trt qua
codon tryptophan v i vo vng 2 (Hnh 7.7B). S c mt ca ribosome
loi b kh nng kt cp ca vng khong 10 base mi pha ca codon
ang dch m. S c mt ca ribosome vng 2 ngn cn n kt cp vi
vng 3. Trong trng hp ny vng 3 kt cp vi vng 4, to ra im kt
thc phin m. S phin m kt thc khi qua cc uridine nm pha sau
vng 4.
Khi s lng tRNAtrp khng , s dch m leader polypeptide b
dng li t ngt cc codon tryptophan. S dng li ny ngn cn
ribosome tin vo vng 2, v vy vng 2 c t do s kt cp vi vng 3
lm cn tr s hnh thnh cu trc kt thc. V vy phn t trp mRNA
hon chnh c to thnh, cha c trnh t m ha cho gene cu trc.
Tm li, attenuation l c ch iu ha tinh t trn c s iu ha m
tnh: Khi tRNAtrp n cung cp cho s dch m leader polypeptide, s
phin m b dng, cc trp enzyme khng c tng hp. Khi nng
tRNAtrp qu thp, s phin m xy ra cho n ht, cc trp enzyme c
to nn.
Nhiu operon chu trch nhim tng hp cc amino acid khc (nh
cc operon ca leucine, isoleucine, phenylalanine, histidine) cng c
iu ha nh attenuator vi chc nng to ra vng kt cp bin i bn
217
phin m. operon histidine vng m ha ca leader polypeptide cha 7

codon histidine k nhau. operon phenylalanine vng m ha cho leader
polypeptide cha 7 codon phenylalanin chia 3 nhm.
trp
codons
S kt cp trong
RNA nng
thp ca
tryptophan
Kt thc
phin m
RNA
polymerase
S kt cp trong
RNA nng cao
ca tryptophan
S kt cp
trong mRNA
Phin m
tip tc
Hnh 7.7 Phin m d (attenuation) ca operon trp E. coli

A. mRNA t do c s kt cp base gia 1-2 v 3-4
B. nng cao ca tryptophan, ribosome tin n vng 2 v s kt cp 3-4
lm kt thc phin m
C. nng tryptophan thp, ribosome vng codon trp cho php kt cp 2-3
v phin m khng b kt thc sau khi qua vng 4
iu ha kiu attenuation khng th xy ra eukaryote v

eukaryote s phin m v dch m khng xy ra ng thi. S phin m
xy ra trong nhn, cn s dch m xy ra t bo cht.
iu ha operon lac v operon trp l v d v mt trong s cc c
ch quan trng iu ha hot ng gene mc phin m ca prokaryote.
III. iu ha biu hin gene eukaryote

iu ha hot ng gene eukaryote phc tp hn nhiu so vi
prokaryote. Lin quan n iu ha, gia prokaryote v eukaryote c mt
s im khc bit:
- eukaryote thng ch c mt chui polypeptide n c dch m
t mt phn t mRNA hon chnh. mRNA a cistron (polycistronic) ch
c prokaryote, khng c eukaryote.
- DNA ca eukaryote gn vi protein histone to si chromatin, v
gn vi protein phi histone. Ch c mt on nh DNA trn.
218
prokaryote, mt vi protein c mt trn nhim sc th b gp np, cn li

hu ht DNA trn.
- Mt on DNA quan trng ca eukaryote cha trnh t nucleotide
lp li trung bnh hoc lp li cao. Mt vi trnh t lp li c xp ni
tip thnh cc bn sao tip ni nhau, mt vi trnh t khc li khng xp
ni tip. Vi khun cha on DNA lp li nh khc cc gene ca rRNA v
tRNA nhn on v mt vi yu t di ng.
Mt on ln DNA ca eukaryote khng c dch m. Hu ht trnh
t nucleotide khng c m ha thnh protein. Cc eukaryote n bo,
chng hn nm men l trng hp ngoi l i vi tnh cht ny.
Mt vi gene eukaryote c biu hin v iu ha nh c ch cu
trc li nhng on DNA nht nh theo mt phng thc c iu
khin v tng s lng cc gene c bit ny khi cn thit.
Cc gene eukaryote l gin on c phn thnh cc exon v intron.
Cc intron c ct b trong qu trnh ch bin bn phin m RNA trc
khi bt u dch m.
eukaryote, mRNA c tng hp trong nhn v c chuyn qua
mng nhn, vo t bo cht mi c s dng. T bo vi khun khng c
nhn c tch bit vi t bo cht.
1. S bin i DNA
Mt s gene ca eukaryote c iu ha bng s bin i DNA.
Chng hn, nhng trnh t nht nh c th c khuych i hoc cu
trc li trong genome hoc cc base c th b bin i v mt ha hc.
Mt vi bin i c phc hi, nhng bin i khc li bn vng. Tuy
nhin nhng thay i bn vng ny thng xy ra t bo sinh dng, v
vy chng khng c truyn li cho th h sau qua dng giao t.
2. Cc promoter
Tng t vi khun, cc promoter ca eukaryote cng nm pha trc
im xut pht trn mRNA v c nhng trnh t c bo tn trong tin
ha. Hp TATA nh hng cho mRNA bt u phin m nm pha
trc im bt u phin m khong 30 bp ng vt c v v 60 n
120 bp nm men. Hp TATA hot ng c hiu qu cng vi 2 trnh t
tng ng pha trc khong 40 bp l CCAAT v 110 bp l trnh t giu
GC. S thay i hp TATA lm gim tc phin m. Hiu qu ca tc
phin m c o bng s thay i ca tng base trong promoter.
* S cu trc li DNA theo chng trnh (programmed DNA
rearrangement)
S cu trc li trnh t DNA trong genome l c ch bt thng
219
nhng quan trng, nh mt s gene c iu ha.

3. Nhng trnh t tng cng phin m (Enhancer)
Cc th th ca hormone v nhng protein hot ha phin m khc
gn vi trnh t DNA c bit c bit l enhancer. Trnh t enhancer
kh ngn (thng ch 20 cp base) c tm thy cc v tr khc nhau
quanh gene c iu ha. Hu ht cc enhancer nm pha di im
bt u phin m (i khi cch xa nhiu kb). Nhng enhancer khc l cc
intron nm trong vng m ha v mt vi enhancer thm ch nm u 3'
ca gene.
Enhancer l thnh phn nhy cm ca t chc gene eukaryote v
chng cho php gene phin m ch khi no c nhn t hot ha phin m
ng. Mt vi enhancer phn ng vi cc phn t bn ngoi t bo, chng
hn hormone steroid to phc hp receptor-hormone. Nhng enhancer
khc phn ng vi cc phn t c to thnh bn trong t bo (chng
hn trong sut qu trnh pht trin). Nhng enhancer ny cho php cc
gene di s iu khin ca n tham gia vo bit ha t bo
(differentiation) hoc c biu hin theo cch c bit trong m. Nhiu
gene di s kim sot ca cc enhancer khc nhau, v vy chng c th
phn ng vi nhiu tn hiu phn t khc nhau c bn trong v bn ngoi.
Vng 5
Enhancers
Untranslated
leader
Promotor
Introns
Exons
Vng 3
Enhancers
Hnh 7.8 S t chc cc gene in hnh eukaryote bc cao
Qua s (Hnh 7.8) cho thy nhiu yu t di truyn c tm thy

trong gene ca eukaryote in hnh. Phc hp phin m bm vo
promotor bt u tng hp mRNA. Vng m ha ca gene (exon) b gin
on bi mt hoc nhiu trnh t gin on (intron), cc trnh t ny s b
loi b trong qu trnh ch bin RNA. S phin m c iu ha bi cc
yu t enhancer, cc yu t ny phn ng vi cc phn t khc nhau c vai
tr l tn hiu cm ng. Enhancer c mt c pha trn v pha di
promoter. Mt vi enhancer c nhiu bn sao.
Nhiu enhancer kch thch phin m bng cch hnh thnh vng DNA
(DNA looping), lin quan n s tng tc gia cc vng cch xa nhau c
lin quan dc si DNA. Cc nhn t cn thit cho phin m bao gm
220
protein hot ha phin m, n tng tc vi t nht mt yu t protein c

trong mt hoc nhiu phc hp protein ln, nhiu yu t. Yu t protein
trong phc hp ny c bit nh l yu t phin m chung (general
transcription factors), v chng gn lin vi s phin m ca nhiu gene
khc nhau. Nhn t phin m chung eukaryote c tnh bo tn cao trong
tin ha. Mt trong s cc phc hp ny l TFIID, gm protein gn vi
hp TATA (TATA-box-binding protein) TBP gn vi promotor trong
vng TATA box. Ngoi TBP, phc hp TFIID cng gm mt s protein
khc c gi l nhng nhn t gn lin vi TBP (TBP-associated factors)
= TAFs. Chng hot ng nh cc cht trung gian qua nh hng ca
nhn t hot ha phin m c truyn i. S phin m cng yu cu mt
holoenzyme l RNA polymerase, cha pol III t hp t nht vi 9 yu t
protein khc. nm men, nhng yu t ny cha nhn t phin m TFIIB,
TFIIF v TFIIH cng nh nhng protein khc.
4. Trnh t bt hot gene (gene silencing)
Trnh t bt hot gene c th nm trc hoc sau gene c iu ha
khong vi trm cp base. Chng lm ngng qu trnh phin m bng cch
bin i histone v DNA.
5. Promoter chn lc (alternative promoter)
Mt vi gene eukaryote c hai hoc nhiu promoter hot ng trong
nhng t bo khc nhau. Nhng promoter khc nhau ny dn n nhng
bn phin m khc nhau cha cng vng m ha protein. V d
Drosophila, gene m ha cho alcohol dehydrogenase, cu to ca n trong
genome c ba vng m ha protein b gin on bi hai intron. S phin
m u trng s dng mt promoter khc vi s phin m rui trng
thnh. Bn phin m rui gim trng thnh c trnh t dn u 5' di
hn. Nhng hu ht trnh t ny b loi b trong splicing. Promoter bin
i lm s iu ha phin m c th khng ph thuc vo u trng hay
rui gim trng thnh.
6. Splicing chn lc
Cng promoter c s dng phin m mt gene, cc loi t bo
khc nhau c th to sn phm c s lng khc nhau hoc to ra nhng
protein khc nhau. iu ny l do cng mt bn phin m c th c qu
trnh ch bin cc loi t bo l khc nhau.
S tng hp -amylase chut, nhng phn t mRNA khc nhau
c to ra t cng mt gene v nhng phn intron khc nhau b loi b
trong qu trnh ch bin RNA. Tuyn nc bt ca chut to nhiu
enzyme hn gan mc d cng mt trnh t m ha c phin m. mi
221
loi t bo, cng mt bn phin m s cp (primary transcript) c tng

hp, nhng c hai qu trnh ch bin khc nhau (Hnh 7.9). Trnh t m
ha bt u 50 bp bn trong exon 2 c to thnh nh ni vi exon 3 v
nhng exon tip theo. tuyn nc bt bn phin m s cp c ch
bin exon S ni vi exon 2 (exon L b loi i nh l intron 1 v 2).
gan exon L ni vi exon 2, exon S b loi i cng vi intron 1. Exon S v
exon L tr thnh nhng trnh t 5' bin i ca amylase mRNA v mRNA
ny c dch m nhng t l khc nhau.
A. Bn phin m s cp
Phin m
amylase ca gan
Qu trnh ch bin
t bo gan
mRNA amylase ca gan
B. Bn phin m s cp
Phin m
amylase ca
tuyn nc bt
Qu trnh ch
bin t bo
tuyn nc bt
mRNA amylase ca
tuyn nc bt
Hnh 7.9 Sn phm cc phn t mRNA amylase khc nhau do qu trnh

splicing khc nhau xy ra t bo tuyn nc bt v t bo gan ca chut.
Cu hi v Bi tp
1. S biu hin gene prokaryote v eukaryote c c im g?
2. Hy nu cc kiu iu ha ch yu.
3. Trnh by c ch hot ng ca operon lactose.
4. Operon l g? Nu ngha ca operon i vi s biu hin ca
gene.
5. Gene m ha cho cht c ch (repressor) ca operon vi khun c
cn thit phi gn gene cu trc khng? Ti sao?
6. So snh iu ha m tnh v iu ha dng tnh ca phin m.
Cho v d.
7. Khi c mt glucose trong t bo E. coli, nng cAMP-CRP nh
222
th no? S gn ca cAMP-CRP vo DNA c nh hng n s gn ca

repressor khng?
8. Nu ngha ca hin tng phin m d (attenuation).
9. Phn bit gia repressor v aporepressor v cho v d.
10. Th no l splicing chn lc? Cho v d minh ha.
Ti liu Tham kho

Ting Vit
Phm Thnh H (2000). Di truyn hc. NXB Gio Dc.
L nh Lng, Phan C Nhn (1998). C s Di truyn hc. NXB Gio
Dc.
Hong Trng Phn (1995). Di truyn hc Phn t. Trung tm o to T
xa, i hc Hu.
Ting Anh
Anthony J. F. Griffiths, Susan R. Wessler, Richard C. Lewontin, William
M. Gelbart, David T. Suzuki, Jeffrey H. Miller. 2004. An introduction to
genetics analysis. W.H. Freeman Publishers.
Harlt D.L., Jones E.W. (1998). Genetics - Principle and analysis. Jone
and Bartlett Publshers. Toronto, Canada.
Stansfield W.D. 1991. Schaums outline of theory and problems of
genetics. McGraw-Hill, Inc., New York.
223
Chng 8
t bin gene, Ti t hp v cc Yu t Di
truyn Vn ng
I. t bin gene
t bin gene l nhng bin i xy ra bn trong cu trc gene. Mi
t bin gene dn n s thay i trnh t nucleotide to ra cc allele khc
nhau. t bin gene c th xy ra do bin i ca trnh t nucleotide trong
gene. t bin gene khng pht hin c khi quan st t bo hc.
Trong t nhin, tt c cc gene u c t bin c gi l t bin t
nhin hay ngu pht (spontaneous mutation). Cc t bin t nhin
thng xut hin rt t.
1. Cc kiu t bin gene
t bin gene hay t bin im: l cc bin i rt nh trn mt
on DNA, thng lin quan n mt cp base n ca DNA hoc mt s
t cp base k nhau. t bin im lm thay i gene kiu di (wild-type
gene),. Thc t t bin im hu nh lm gim hoc lm mt chc nng
ca gene hn l lm tng cng chc nng ca gene.
V ngun gc, t bin im c phn ra lm t bin ngu pht
(spontaneous) v t bin cm ng (induced).
t bin cm ng: l dng t bin xut hin vi tn s t bin tng
ln khi x l c mc ch bng tc nhn t bin hoc tc nhn mi trng
c bit. t bin ngu nhin l t bin xut hin khi khng c s x
l ca tc nhn t bin. t bin ngu nhin c tnh l t l c s ca
t bin v c dng c chng ngun bin d di truyn t nhin
trong qun th. Tn s t bin ngu nhin thp nm trong khong 10-5 10-8, v vy t bin cm ng l ngun t bin quan trng cho phn tch
di truyn.
Tc nhn t bin c s dng ph bin l ngun chiu x nng
lng cao (high-energy radiation) hoc cc ha cht c bit.
Cc dng t bin im: c hai dng t bin im chnh trong phn
t DNA:
+ t bin thay th cp base (base substitution)
+ t bin thm-bt cp base (base insertion - base deletion)
Cc t bin ny c th pht sinh do nh hng ca mi trng nh
nh hng ca cc tc nhn gy t bin.
224
1.1. t bin thay th cp base

Kiu t bin n gin nht l thay th mt base, trong mt cp
nucleotide trong gene c thay th bng mt cp nucleotide khc.
V d: A c thay th bng G trong si DNA. S thay th ny to ra
s cp base G-T. ln sao chp tip theo to ra cp G-C trong mt phn
t DNA con v cp A-T phn t DNA con kia.
Tng t, t bin thay th A bng T trn mt si, to ra s kt cp
tm thi T-T. Kt qu sao chp to ra T-A trn mt phn t DNA con v
A-T trn phn t DNA con kia. Trong trng hp hp ny, cp base T-A
l t bin v cp A-T khng t bin. Nu si gc DNA khng t bin
c trnh t 5'-GAC-3', trn si t bin c trnh t 5'-GTC-3' v si kia
khng t bin c trnh t 5'-GAC-3'.
t bin thay th cp base c chia lm hai loi:
+ t bin ng hon (transition mutations): Nu mt t bin m
base pyrimidine c thay th bng mt pyrimidine v mt purine thay
bng mt purine.
t bin ng hon c th l:
T C hoc C T
(Pyrimidine pyrimidine)
A G hoc G A
(purine purine)
t bin o hon (Transversion): t bin lm thay mt pyrimidine
thnh mt purine hay mt purine c thay th bng mt pyrimidine. Cc
t bin o hon:
T A, T G, C A hoc C G
(Pyrimidine purine)
A T, A C, G T hoc G C
(Purine pyrimidine)
Nh vy c th c 4 thay th kiu t bin ng hon v c n 8
thay th kiu t bin o hon. Nu cc thay th ny xy ra vi ngu
nhin xc sut nh nhau, s c t l t bin: 1 ng hon : 2 o hon.
Tuy nhin trong thc t, t bin thay th base c xu hng nghing v
t bin ng hon, cho nn trong s cc t bin thay th base t pht th
t l xy ra t bin l: 2 ng hon : 1 o hon
1.2. t bin thm hoc bt base (base-pair addition/deletion), cn gi l
indel mutation (insertion-deletion). Trng hp n gin nht ca t bin
225
ny l thm hoc mt mt cp base n. i khi t bin lm thm hoc

mt ng thi nhiu cp base.
Hu qu ca t bin im n cu trc v s biu hin ca gene
t bin im xut hin trong vng m ha chui polypeptide ca
gene (a polypetide-coding part of a gene), chng hn t bin thay th
base n c th gy nhiu hu qu, nhng tt c u c tc ng ln m di
truyn theo 2 hng: lm thoi ha m di truyn hoc xut hin m kt
thc qu trnh dch m. C cc dng:
t bin ng ngha (synonymous mutations): t bin thay i mt
codon m ha acid amine thnh codon mi m ha cho cng acid amin .
t bin ng ngha cng c th xem l t bin im lng (silent
mutations)
t bin nhm ngha (missense mutations), i khi cn gi l t
bin khng ng ngha (nonsynonymous mutations): codon m ha cho
mt acid amin ny b thay i thnh codon m ha cho mt acid amin
khc.
t bin v ngha (nonsense mutations): codon m ha cho mt acid
amin b thay i thnh codon kt thc dch m (translation
termination/stop codon).
Mc nh hng ca t bin nhm ngha v v ngha ln chui
polypeptide khc nhau ty trng hp.
Nu t bin nhm ngha thay th mt acid amin ny bng mt acid
amin khc tng t v mt ha hc, c xem l t bin thay th bo th
(conservative substitution). S thay i ny hu nh t nh hng n cu
trc v chc nng protein. Ngc li, nu thay th bng mt acid amin
khc v phng din ha hc gi l nonconservative substitution, hu ht
u gy ra s thay i ln cu trc v chc nng protein.
t bin v ngha s dn n s kt thc dch m sm. V vy chng
gy ra hu qu tng ng trn chc nng protein. Nu t bin v ngha
xy ra cng gn u 3' ca khung c m, kt qu t nh hng n
protein. Tuy nhin nhiu t bin v ngha vng ny vn to ra cc sn
phm hon ton b mt hot tnh.
226
Bng 8.1 t bin im mc phn t

Kiu t bin
mc DNA
ng hon
Kt qu v v d
Purine c thay th bng mt purine khc,
pyrimidine c thay th bng mt pyrimidine
khc: AT GC, GC AT, CG TA,
TA CG
o hon
Purrin c thay th bng mt pyrimidine hoc

mt pyrimidine c thay th bng mt purine:
AT CG, AT TA, GCTA, GCCG
TAGC, TA AT, CG AT, CGGC
Thm/Mt
(Insertion-deletion)
Thm vo hoc mt i mt hoc mt s cp base

ca DNA (thm/mt base c gch di)
AAGACTCCT AAGAGCTCCT
AAGACTCCT AAACTCCT
mc protein
t bin ng ngha
Codon c bit m ho cho cng mt acid amin:
t bin nhm ngha

Loi bo th
Codon to thnh m ho cho amino acid khc

M ho cho acid amin c cng bn cht ho hc:
Loi khng bo th
AAA AGA
Lys
Arg
(kim)
(kim)
M ho cho amino acid khc v bn cht ho
hc:
UUU
UCU
Phenylalanin
Serine
K nc
Phn cc
t bin v ngha
Codon kt thc chui:
t bin dch khung
Thm vo mt cp base:
AAG ACT CCT AAG AGC TCC T...
Mt mt cp base:
AGG CGG
Arg
Arg
CAG UAG
Gln
Stop
AAG ACT CCT AAA CTC CT...
227
Gene kiu di
t bin thay
th base
t bin dch
khung
Protein iu ha khng th bm
im t bin trong
trnh t khng m
ha
Hnh 8.1 Hu qu ca t bin im trong gene. Codon 1-4 nm trong vng

m ha ca gene.
Ging vi t bin v ngha, t bin thm bt base gy hu qu trn

trnh t polypetide k t im b t bin (Hnh 8.1). Trnh t trn mRNA
c c theo tng khung gm ba base (codon) mt lc. Mt hoc thm
base s lm thay i khung c trong qu trnh dch m t im b t
bin cho n kt thc theo khung mi. V vy loi t bin ny c gi
l t bin dch khung (frameshift mutations). t bin ny to ra trnh t
acid amin k t im b t bin cho n kt thc khc vi trnh t acid
amin gc. t bin dch khung gy ra s mt hon ton cu trc v chc
nng ca protein bnh thng.
Trng hp t bin xy ra trnh t iu ha v cc trnh t khng
m ha khc (Hnh 8.1). Nhng phn ca gene khng trc tip m ha
cho protein m cha nhiu im bm DNA ch yu cho protein xen vo,
l nhng trnh t khng nhy cm cho s biu hin ca gene hoc cho
hot tnh ca gene.
228
mc DNA, nhng im mt i (docking) gm nhng im m

RNA polymerase v nhng nhn t gn kt ca n bm vo, cng nh
nhng im m protein iu ha phin m c trng gn vo. mc
RNA, nhng docking quan trng thm vo gm im bm ca ribosom
(ribosome-binding site) trn mRNA vi khun, nhng im ni u 5' v 3'
gn cc exon eukaryote v cc im c vai tr cho iu ha dch m
v nh v mRNA n vng c bit trong t bo. Nhn chung hu qu
chc nng ca bt k t bin im no vng nh th u ph thuc vo
vic lm gin on (hoc to ra) mt im bm. t bin lm gin on
nhng im c kh nng lm thay i phn biu hin ca gene da vo
s thay i s lng sn phm c biu hin mt thi im nht nh
hoc mt m nht nh. hay bng s thay i phn ng vi nhng tn
hiu (cue) ca mi trng nht nh. Ngc li, t bin mt vi im
bm c th hon ton ph hy mt giai on cn cho s biu hin bnh
thng ca gene, nh im bm ca mRNA polymerase hoc l nhn t
splicing. V vy n lm bt hot sn phm ca gene hoc ngn cn s hnh
thnh sn phm.
Cn phn bit gia nhng thay i xy ra ca mt t bin gene l
s thay i trnh t DNA ca gene vi s thay i mc kiu hnh.
Nhiu t bin im trong trinh t khng m ha lm t thay i hoc
khng thay i trn kiu hnh nh t bin gia im bm DNA cho
protein iu ha hoc thay i nhng im khc trong gene lm thay i
chc nng ca chng.
2. Cc tc nhn gy t bin gene
2.1. Cc tc nhn gy t bin vt l
- Phng x ion ha: cc tia phng x , , hoc tia X, cc chm tia
neutron hoc proton lm bn cc in t gy ion ha v bin i DNA.
- Phng x khng ion ha: tia t ngoi (UV) hoc nhit lm tng mc
nng lng ca nguyn t. Tia t ngoi thng to dimer thymine gn hai
thymine k nhau ca mt mch.
2.2. Cc tc nhn gy t bin ha hc
- To sai hng khi sao chp: cc cht ng ng ca base (bromouracil, 2-amino purine) gn vo sai khi sao chp c chng. Cc cht
mu acridine c th gn vo gia cc base ca mch xon kp lm mt
hay thm vo mt base.
- Tc ng trc tip ln gene khi khng c cc sao chp c th gy
t bin im hay cc bin i A-T G-C hoc G-C A-T.
3. C ch phn t ca cc t bin gene
229
Khi kim tra dy t bin c gy to bi cc tc nhn t bin khc

nhau cho thy mi tc nhn t bin c c trng bi mt c tnh t
bin khc nhau hay "preference" v c mt dng t bin nht nh v mt
im t bin nht nh, c gi l im d xy ra t bin (mutational
hot spots). c tnh t bin nh th c ch ln u tin locus rII
ca bacteriophage T4.
Tc nhn t bin hot ng t nht qua ba c ch khc nhau: chng
c th lm thay th mt base trong DNA; lm bin i mt base gy kt
cp nhm vi mt base khc; lm sai hng mt base, dn n khng th
kt cp vi bt k base no trong iu kin bnh thng.
t bin thay th base: mt vi hp cht ha hc tng t nitrogen
base bnh thng ca DNA, i khi chng c th gn vo DNA thay cho
base bnh thng. Nhng cht nh th c gi l cc cht tng ng
vi base (base analogs). Cc cht tng ng ny kt cp khng nh s
kt cp ca cc base bnh thng. V vy chng c th gy ra t bin do
gn vo mt nucleotide khng ng trong qu trnh sao chp.
Dng keto ph
bin ca 5BU
Adenine
Dng keto ph
bin ca 5BU
Dng enol
him ca 5BU
Hnh 8.2 Chng minh mt vi kt cp nhm c th xy ra do kt qu ca

s thay i mt tautomer thnh mt tautomer khc.
hiu hot ng ca cc cht tng ng base, trc ht cn phi

xem xt khuynh hng t nhin ca cc base i vi s hnh thnh cc
dng khc nhau. Mi base trong phn t DNA c th xut hin mt
trong s nhiu dng c gi l tautomers, chng l cc ng phn khc
nhau v tr v tr nguyn t v nhng lin kt gia cc nguyn t. Dng
keto ca mi base thng c trong DNA (Hnh 8.2), trong khi dng imino
v enol ca base l him. Tautomer imino hoc enol c th kt cp sai vi
base to mt kt cp nhm (mispair). Kh nng kt cp nhm nh th gy
ra t bin trong qu trnh sao chp c ch u tin bi Watson v
Crick khi cc tc gi ny nghin cu cng thc v m hnh cu trc DNA.
230
S kt cp nhm c th sinh ra ngu nhin, nhng cng c th sinh ra

khi base b ion ha. Tc nhn gy t bin 5-bromouracil (5-BrU) l cht
tng ng vi thymine, c brome v tr carbon s 5 thay cho nhm CH3 ca thymine. Hot tnh ca n da trn qu tnh inolization v
ionization. dng keto, 5-BrU kt cp vi adenin nh trng hp
thymine. Tuy nhin, s c mt ca nguyn t bromine lm thay i mt
cch c ngha s phn b electron vng base. V vy 5-BrU c th
chuyn sang dng enol v dng ion, v n c th kt cp vi guanine nh
trng hp cytosine to ra cp 5-BrU-G. Trong ln nhn i tip theo G
kt cp vi C, to cp G-C thay cho cp A-T. Kt qu gy ra t bin ng
hon. Tng t 5-BrU cng c th gy ra t bin ng hon A-T thay
cho cp G-C.
Mt ha cht gy t bin khc l 2-amino-purine (2-AP), l ha cht
tng ng adenine, c th kt cp vi thymine. Khi b proton ha, 2-AP
c th kt cp nhm vi cytosine, c th gy ra th h sau t bin ng
hon G-C thay cho A-T do kt cp nhm vi cytosine trong ln sao chp
tip theo.
- Thay th base (base alteration)
Mt vi tc nhn t bin khng gn vo DNA, m li lm bin i
base gy ra s kt cp sai. Tc nhn alkyl c s dng ph bin nh l
tc nhn t bin, chng hn nh ethylmethanesulfonate (EMS) v
nitrosoguanidine (NG) gy t bin theo cch ny.
Nhng tc nhn nh th s thm nhm alkyl (nhm ethyl trong
trng hp EMS v nhm methyl trong trng hp NG) nhiu v tr trn
c 4 base. Tuy nhin, t bin hu nh ch xy ra khi nhm alkyl c
thm vo oxy s 6 ca guanine to ra O-6-alkylguanine. S alkyl ha
ny dn n s kt cp nhm vi thymine (Hnh 8.3). Kt qu sinh ra t
bin ng hon G-CA-T trong ln sao chp tip theo.
Tc nhn xen vo gia (intercalating agents) l nhm tc nhn quan
trong khc gy bin i DNA. Nhm ca cc hp cht ny bao gm
proflavin, acridin cam v mt nhm cc hp cht ha hc khc. Cc tc
nhn ny l nhm cc phn t bt chc cc cp base v c th xen vo
gia cc base nit li chui xon kp DNA. v tr xen vo ny chng
gy s thm vo hoc mt i mt cp nucleotide.
- Sai hng base
Mt s ln tc nhn t bin gy sai hng mt hoc nhiu base. V
vy khng th kt cp vi base c trng. Kt qu lm cn tr s sao chp
v DNA polymerase khng th tip tc qu trnh tng hp DNA qua
231
nhng base sai hng. E.coli qu trnh ny xy ra i hi hot tnh ca h

thng SOS. H thng ny c kch thch nh l mt phn ng khn cp
ngn cn s cht t bo khi DNA b sai hng nng.
Hnh 8.3 S kt cp nhm chuyn bit do t bin cm ng alkyl ho.
* C ch ca t bin ngu nhin

t bin ngu nhin xy ra do nhiu nguyn nhn: gm sai hng
trong qu trnh sao chp DNA, cc tn thng ngu nhin, s chen vo
ca yu t di ng. t bin ngu nhin him nn kh xc nh c ch c
bn. Tuy nhin, mt vi h thng chn lc cho php thu c t bin
ngu nhin v phn tch mc phn t. T bn cht ca nhng thay
i trnh t c th suy ra qu trnh dn n t bin ngu nhin.
Nhng sai hng ngu nhin (spontaneous lesions) n DNA c th
sinh ra t bin. Hai tn thng ngu nhin thng xut hin nht:
depurine ho v deamin ho, trong depurine ho ph bin hn.
Depurination do tc dng ca aflatoxin, lm mt mt base purine.
Ngoi ra, qu trnh mt purine cng xy ra mt cch t nhin. Mt t bo
ng vt mt ngu nhin khong 10.000 purine ca DNA trong mt th h
t bo khong 20 gi 37oC. Nu tn thng ny c gi li, dn n
sai hng di truyn ng k v trong qu trnh sao chp, v tr mt purine
khng th nh r c loi base no. Trong nhng iu kin nht nh
mt base c th chn vo to ra t bin.
232
Deamination ca cytosine to ra uracil. Uracil s kt cp vi adenin

trong qu trnh sao chp, kt qu to ra t bin ng hon G-C A-T.
Deamination 5-methylcytosine to ra thymine (Hnh 8.4). Qu trnh sao
chp to ra t bin ng hon chuyn C thnh T.
Hnh 8.4 Deamination ca Cytosine (a) v 5-methylcytosine.
Ngoi 2 qu trnh gy sai hng nh trn, s oxy ha to ra cc base b

sai hng l dng tn thng th ba.. Dng oxygen hot ng nh gc
superoxid (O2-), hydrogen peroxide (H2O2) v gc hydroxyl (-OH) c
to ra do sn phm ca qu trnh chuyn ha (aerobic metabolism). Cc
dng ny c th gy tn thng oxy ha n DNA, kt qu to ra t bin.
Cc sai hng trong sao chp DNA cng l ngun t bin khc.
- Thay th base: sai hng trong sao chp DNA c th xy ra khi c
mt cp nucleotide ghp khng chnh xc (nh A-C) to ra trong qu trnh
tng hp DNA dn n s thay th mt base.
- t bin thm vo v mt base: Mt loi sai hng sao chp khc dn
n thm vo hoc mt mt hoc mt s cp base. Trong trng hp s
base thm vo hoc mt i khng chia ht cho 3, s to ra t bin dch
khung trong vng m ha protein.
II. Sa cha v bo v DNA

* C ch sa sai sinh hc
T bo sng c hng lot h thng sai hng DNA theo nhiu cch
233
khc nhau. T l t bin t nhin thp do nh tnh hiu qu ca h thng

sa sai ny. Sai hng ca h thng sa sai ny dn n t l t bin cao.
Quang phc hot (photoreactivation) hay sa sai nh nh sng (light
repair)
B khung DNA
nh sng
trng
Tia cc tm
Hnh 8.5 S to thnh v s loi b dimer thymine.
Sau khi x l tia t ngoi gy t bin, nu a ra nh sng th phn

ln sai hng c phc hi nh enzyme photolyase. Enzyme ny gn vo
photodimer ct n thnh cc monomer di tc dng ca nh sng mt
tri c bc sng 320-370 nm. Sau phc hi cc base ban u. (Hnh
8.5).
Sa sai bng lm mt nhm alkyl (dealkylation)
Enzyme alkyltransferasecos th sa trc tip cc sai hng. Chng ct
nhm alkyl t cht nitrosoguanine v ethylmethnesulfonate v gn vo v
tr O-6 guanine.
Enzyme methyltransferase ca E. coli c kh nng chuyn nhm
methyl t cht O-6 methylguanine sang gc cistein trn phn t protein.
Tuy nhin h thng sa sai ny c th bo ha nu mc alkyl ha
cao.
Sa sai bng ct b (excision repair pathway)
Phn ln cc c ch sa sai khc thc hin theo li ct b (excistion
repair) khng cn nh sng nh cc nuclease, sau thay vo cc base
ng. C th xy ra theo nhiu cch:
234
- Ct cc base (base excision repair)
uvrABC exonuclease ct b on
DNA 12 nucleotide
DNA polymerase I tng hp

on DNA mi
Ligase ni
ch h
Hnh 8.6 Sa sai bng ct b nucleotide.
S ct b cc base sai hng nh cc enzyme DNA glycosylase. Cc

enzyme ny nhn bit cc base b bin i v cc im mt purine hay mt
pyrimidine v thy gii lin kt N-glycosilic ni base vi ng. Ri
enzyme AP endonuclease ct lin kt ng v phosphate gn base b bin
i. Sau enzyme th ba, deoxyribophosphodiesterase loi b tng
nucleotide k tip nhau on b hng. Sau , DNA polymerase lp y
khong trng vi cc nucleotide b sung vi si khun cn li. Enzyme
DNA ligase s gn cc khe h gia 2 u 3'-5' (Hnh 8.6).Trong t bo tn
ti mt s DNA glycosylase. Chng hn, enzyme uracil-DNA glycosylase
ct uracil khi DNA. Uracil to thnh do t bin mt nhm amin ngu
nhin cytosine, dn n t bin ng hon thay C bng T. Enzyme ny
pht hin ra uracil trn DNA nh l mt bt thng, chng s ct b v
sa sai.
- Ct cc nucleotide: S ct b vng c nhiu pyrimidine dimer c
thc hin nh enzyme exonuclease (enzyme rch mch hay enzyme to
khc trn DNA) nh phc hp 3 enzyme c m ha bi gene uvr ABC
ca E. coli. Phc hp ny ct on 12 nucleotide trn mt mch: 8
nucleotide t mt u b sai hng v 4 nucleotide ca u cn li. Khong
trng ca 12 nucleotide ny s c lp y nh enzyme DNA
polymerase I da vo mch n b sung kia ca trnh t DNA gc. DNA
ligase s gn vo cc khe h.
235
- c sa i vi cc base bt cp sai
C ch c sa i vi cc base bt cp sai (proofreading for basepair matching) c thc hin trong sao chp DNA. Trong qu trnh sao
chp, trc khi thc hin phn ng polymer ha ni cc nucleotide, cc
nucleotide triphotphate mi phi bt cp b sung vi mch khun. Nu s
bt cp sai xy ra, DNA polymerase s loi b nucleotide bt cp sai.
Ngay c trc khi nucleotide mi rp vo, enzyme d li cp base cui,
nu chng khng bt cp th s polymer ha tip theo b dng. Cp
nucleotide u cui 3' bt cp sai s b loi b nh hot tnh
exonuclease3'5' ca DNA polymerase. Khi bt cp ng, qu trnh
polymer ha mi c tip tc.
Hot tnh c sa i vi cc base bt cp sai l c tnh ca nhiu
DNA polymerase m bo cho s ko di chnh xc ca mch ng c
tng hp.
+ Sa sai da vo tnh tng ng (Homology-dependent repair
system)
Mt h thng sa sai quan trng pht hin tnh cht b sung i
song song ca 2 mch n DNA phc hi on sai hng tr li trng
thi bnh thng ban u. Trong h thng ny, on DNA sai hng b ct
b v thay bng mt on nucleotide mi c tng hp b sung vi si
khun i din. S sa sai xy ra qua si khun v nguyn tc ca sao
chp DNA bo m s sa sai hon thnh vi chnh xc cao - l s
gii phng sai hng (error-free). C 2 h thng ch yu loi b sai
hng: H thng sa cha sai hng pht hin ra trc khi sao chp v h
thng sa cha sai hng pht hin trong qu trnh din bin sao chp (sa
sai sau sao chp).
+ Sa sai t mch kp (repair of double-strand break)
Khi c 2 si ca chi xon kp b t cng mt v tr, c gi l
t bin t mch i, c th gy ra sai hnh nhim sc th, lm cht t
bo hoc to ra trng thi tin ung th. T bo s dng nhiu protein v
con ng sa sai t gy mch i l thc hin ti t hp trong gim
phn. Qu trnh sa cha do trao i cho trong gim phn xy ra nh sau
(Hnh 8.7):
Trn mt nhim sc th xy ra s t mch i v kt qu n mn cc
u mt on ngn ca DNA si n. u 3' ca mt trong nhng si
ny "xm ln" vo mt chromatid.
236
chromatid a
Chui DNA xon kp
chromatid A
Chui DNA xon kp

u 3
S b gy si i
v ct u cui
S b gy, xm ln
v to vng
S di chuyn
vng v tng hp
Cu trc Holliday
Lp y khong trng
v lin kt cc u t
Heteroduplex vi
ch ghp nhm
B gy v ni u
2 vi u 3
Sa cha A
B gy v ni
u 2 vi u 4
Sa cha A
Kt qu khng trao i cho

Trao i cho kp hon ton
y s l mt
y s l mt
Nu
khng
sa
cha
octad 6:2
octad 6:2
A/a s to ra octad 5:3
Hnh 8.7 M hnh b gy si i nh trao i cho.
on xm ln lm mi cho tng hp cc base b mt ca n nh s

dng si i song song ca chromatid nh l si khun. S tng hp mi
ny s to ra mt vng si n lai vi mt si n khng xm ln. V vy
to ra mt vng d hp t nh "Aa" v s dng nh mch khun khi
phc cc base b mt trn si . DNA polymerase s lp y ch trng v
enzyme ligase s ni cc u mt xy ra trong cu trc c bit ging vi
trao i cho 2 si n. Cu trc ny cng cha cc on bt cp khng
tng ng n gin.
Trao i cho si n c gi l cu trc Holliday (Holliday
structure) do Holliday pht hin vo nhng nm 1960.
H thng SOS
237
t bo vi khun hoc t bo eukaryote b sai hng nng do chiu tia

uv, tia X hoc do tc dng ca cc ha cht gy t bin, h thng sa sai
khn cp c khi ng. E. coli, h thng ny c lin quan vi hai
protein c m ha bi gene lexA v recA. Protein lexA l mt cht c
ch, n gn vo hp SOS, chng lp cc promotor ca cc gene SOS, ngn
cn s phin m nhm cc gene ca h thng SOS. Mt vi sn phm ca
DNA b tn thng s lm hot ha enzyme protease recA. Protein recA
b hot ha s ct b protein lexA, cho php cc gene ca h thng SOS
phin m. Phn ng ca h thng SOS xy ra trong thi gian ngn nhng
phc tp. N bao gm cc qu trnh lm tng hot tnh ti t hp, thay i
trong khi s sao chp, c ch nuclease v kch thch phc hi sao chp v
chuyn sai hng thnh sa sai p sp (error-prone replication). T bo by
gi s xy ra s sao chp DNA nhanh hn bnh thng. Nu sa sai khng
kp, t bo phi chp nhn hoc b t bin hoc b cht.
III. Cc yu t di truyn vn ng (Transposable genetic elements)
1. Cc yu t di truyn vn ng prokaryote
Trnh t on xen (insertion sequence) ca vi khun
Trnh t xen on l mt on DNA ca vi khun di chuyn t mt v
tr trn nhim sc th n v tr mi trn cng nhim sc th hoc trn
nhim sc th khc. Khi xen vo gia gene, yu t IS lm gin on trnh
t m ha v lm bt hot s biu hin ca gene. Mt s trng hp, c
tn hiu kt thc phin m v dch m, yu t IS lm cn tr s biu hin
sau promotor trong cng operon..
Yu t IS c tm thy u tin operon gal ca E. coli, chia lm
bn nhm: IS1, IS2, IS3 v IS4. Chng c th phn b ri rc trn nhim
sc th chnh ca vi khun v trn cc plasmid. V d yu t IS1 c
khong 5-8 bn sao trn nhim sc th vi chiu di 768 bp.
Tt c cc yu t IS u cha on DNA m ha cho protein, c
gi l transposase, l enzyme cn thit cho s di chuyn ca yu t IS t
mt v tr trn nhim sc th n v tr khc. on gene ny nm gia 2
on lp li o ngc (inverted repeat - IR) ngn. V d yu t IS1 c
khong 5-8 bn sao trn nhim sc th vi chiu di 768 bp, on lp li
o ngc c kch thc 18-23 bp, yu t IS2 c 5 bn sao v cc yu t
IS khc. Yu t IS l nhng vng ca cc trnh t xc nh, chng l
nhng v tr xy ra trao i cho. V d: S ti t hp ca plasmid v
nhim sc th ca E. coli to ra nhng chng Hfr xy ra qua trao i cho
n gia yu t IS trn plasmid v yu t IS trn nhim sc th.
238
Bng 8.2. Mt vi trnh t xen vo v kch thc ca chng

Trnh t
xen vo
S bn sao trong E. coli
Chiu
di (bp)
on lp li o
ngc (bp)
IS1
5-8 bn sao trn nhim sc th
768
18-23
IS2
5 bn sao trn nhim sc th,

1 bn sao trn plasmid
1327
32-41
IS3
5 bn sao trn nhim sc th,

2 bn sao trn plasmid
1400
32-38
IS4
1-2 bn sao trn nhim sc th,
1400
16-18
IS5
Cha bit
1250
Ngn
1.1. Gene nhy ca prokaryote

Cc yu t IS ring l khng ch c kh nng t di chuyn m khi hai
yu t ny nm gn nhau th chng c th vn ng nh mt n v
hon chnh v mang theo cc gene nm gia chng. Cu trc phc tp ny
c gi l transposon. C hai kiu transposon vi khun:
(a) Transposon hn hp
(b) Transposon n gin
Hnh 8.8 c trng v cu trc ca transposon hn hp (composite

transposon) v transposon n gin (simple transposon).
Transposon hn hp (composite transposon) cha nhiu gene nm

gia 2 trnh t IS gn nhau, c hng ngc nhau to ra trnh t lp li
o ngc (inverted repeat = IR). Mt trong 2 yu t IS m ha cho
transposase xc tc cho s chuyn v ca c transposon. Chng hn Tn10
l transposon hn hp mang gene m ha cho tnh khng khng sinh
tetracyline. Gene ny nm gia hai yu t IS10 c hng ngc nhau.
239
Transposon n gin (simple transposon) gia cc trnh t IR,

nhng nhng trnh t ny ngn (<50 bp) v khng m ha cho
transposase. S chuyn v ca chng khng phi l kt qu ca s lin kt
vi yu t IS. Cc transposon n gin m ha transposase ring thm
vo mang cc gene ca vi khun. Tn3 l mt transposon n gin (Hnh
8.8).
Transposon hn hp v transposon n gin u cha cc gene thm
vo lin quan n chc nng mi t bo vi khun. C hai loi ny
thng c gi chung l transposon. Transposon di hn yu t IS,
thng cha vi kb), chng cha cc gene m ha cho protein thm vo.
1.2. C ch ca s chuyn v
u tin, transposase ct vt hnh ch chi qua 5 cp base (khc vi s
ct ca enzyme restriction endonuclease) vi tr DNA mc tiu (target site
DNA) (Hnh 8.9). Tip theo l s hi nhp ca transposon qua trung gian
ca transposase, transposon xen vo gia cc u mt ca ch chi. u li
ra ca si n c s dng nh l khun tng hp si b sung th hai.
S gn vo to s sao chp 5 cp base, c gi l s sao chp im mc
tiu (target site duplication).
Hu ht cc yu t di ng ca prokaryote u s dng mt trong 2
c ch chuyn v l sao chp (replicative) v bo th (conservative) hay
khng sao chp. Trong con ng sao chp (nh Tn3), mt bn sao mi
ca yu t di ng to ra khi chuyn v, kt qu l mt bn sao v tr mi
v bn sao cn li v tr c. Trong con ng bo th (nh trng hp
Tn10) khng c s sao chp. Thay vo , yu t c ct ra t nhim sc
th hoc plasmid v c gn vo v tr mi. Con ng ny cn c gi
l con ng "ct v dn" (cut and paste)
2. Cc yu t di truyn vn ng eukaryote
Cc yu t di truyn vn ng eukaryote chia lm 2 nhm: nhm l
cc retrotransposon v nhm 2 l cc DNA transposon.
2.1. Cc retrotransposon
Gery Fink v cs. l nhng ngi u tin s dng nm men nghin cu
iu ho hot tnh gene eukaryote. Cc tc gi ny phn lp c
hng ngn t bin gene HIS4 m ha enzyme tham gia tng hp
histidine. Trong s hn 1.500 t bin ngu nhin HIS4 c tm thy c
2 t bin c kiu hnh khng bn vng. Cc t bin khng bn vng ny
c tn s phc hi li dng kiu di cao 1.000 ln hn cc t bin HIS4
khc. Nhng t bin ny cho on DNA ln xen vo gene HIS4, s xen
vo ny c thc hin do mt trong cc yu t l Ty ca nm men. C 35
240
bn sao ca yu t xen on gi l Ty1 genome ca nm men.
Transposase ct on
DNA mc tiu
Yu t transposon
xen vo
Lm y cc ch
trng
Yu t lp li trc tip 5
cp base 2 u
Hnh 8.9 S nhn i on trnh t DNA ngn im xen vo.
Vic to dng nhng yu t ny t cc allele t bin cho thy xen

on ny khng ging vi yu t IS hoc transposon ca vi khun. Thay
vo chng c c tnh ca retrovirus (virus ca ng vt). C s ging
nhau trong cu trc v thnh phn gene ca retrovirus v yu t Ty1 c
phn lp t t bin HIS4. Ging vi retrovirus, transposon ca nm men
c lp on cui di (long terminal repeat sequence) LTRs, cha hng
trm cp base, c gi l trnh t nm 2 pha on m ha, c hai u
cha gene gag v gene pol. Retrovirus c t nht 3 gene m ha cho 3
protein trong qu trnh sao chp: gene gag m ha cho mt protein c vai
tr lm bin tnh RNA genome. Gene pol m ha enzyme reverse
transcriptase. Gene env m ha cho protein v. Yu t Ty ch cha gene
gag v gene pol, khng cha gene env. (Hnh 8.10).
241
M hnh v s chuyn v nh retrotransposon. Mt bn phin m

RNA t retrotransposon di tc dng ca enzyme phin m ngc to
thnh DNA nh enzyme reverse transcriptase c m ha bi
retrotransposon. Bn sao DNA c chn vo v tr mi trn b gene.
on lp li trc tip 5 bp
ca DNA mc tiu
Phin m NST khc
Bn sao Ty1
xen vo
Dch m
Phin m ngc
Enzyme phin m ngc
Hnh 8.10 S chuyn v nh retrotransposition.
Vo nm 1985, J.Bocke v G. Fink chng minh, yu t Ty1, ging

vi retrovirus, thc hin vic di chuyn qua trung gian RNA. Chng bt
u bng bin i yu t Ty1 ca nm men c to dng trn plasmid.
Trc tin mt u mt ca yu t, c s xen vo mt promotor c
hot ha nh thm galactose vo mi trng. Th hai, mt intron t mt
gene khc ca nm men c a vo vng m ha ca transposon Ty. S
thm vo galactose lm tng tn s chuyn v ca yu t Ty bi bin i.
iu ny lm tng s lng RNA, v galactose kch thch phin m RNA
Ty bt u t promotor nhy cm galactose.
Nhiu t bin ngu nhin c phn lp rui dm cho thy cng
cha retrotransposon. Yu t copia ca rui dm cu trc tng t vi yu
t Ty ca nm men. Chng xut hin t 10-100 v tr trn b gene ca rui
dm. Nhng t bin nht nh ca rui dm l kt qu ca s xen vo ca
yu t copia v nhng yu t khc. Chng hn, t bin white-apricot (wa)
v mu mt ca rui dm to ra do s xen vo yu t ca h copia locus
white.
242
S xen retrotransposon LTR vo cc gene thc vt nh ng, cng

gp phn to ra cc t bin ngu nhin.
2.2. DNA transposon
Nhiu yu t di ng c tm thy eukaryote chuyn v bng c
ch ging vi vi khun. Bn thn yu t IS v transposon hoc l bn sao
ca chng c th xen vo v tr mi trn genome. Cc yu t di chuyn
theo cch ny c gi l yu t nhm 2 hoc DNA transposon. Yu t di
ng c McClintock pht hin u tin ng l cc DNA transposon.
Tuy nhin tnh c trng phn t ca DNA transposon u tin li l yu
t p rui dm.
Yu t p c pht hin khi nghin cu th lai mt kh nng sinh sn
(dysgenesis), hin tng xy ra khi lai rui ci thuc chng phng th
nghim vi rui c qun th t nhin. Trong php lai nh th, chng
phng th nghim c xem l c kiu t bo M (M cytotype) v ging
gc t nhin c xem l c kiu t bo P (P cytotype). Php lai ca M
(ci) x P (c) cho th h sau kiu hnh dng mm vi gm dng bt th
vi t l t bin, tn s sai hnh nhim sc th v khng chia ly nhim sc
th cao. Php lai nghch khng xy ra hin tng thoi ha ging
(dysgenics). t bin dysgenics khng bn, chng c th phc hi dng
kiu di hoc bin i thnh allele t bin khc vi tn s cao.
S ging nhau v t bin khng bn vng rui dm v ng a
n gi thuyt t bin dysgenic c gy ra do s xen yu t di ng vo
nhng gene c bit, lm chng b bt hot. Chng hn hu ht cc t
bin trn rui dm do xen yu t di ng vo gene white. Nhng yu t
nh vy gi l yu t p, c t 30-50 bn sao trn genome chng P v
hon ton vng mt chng M. Yu t P c chiu di t 0,5-2,9 kb. Kch
thc khc nhau ny do do nhiu yu t P khng y m b mt on
gia. Yu t P vi kch thc y tng ng vi transposon n
gin vi khun, c u mt l on lp o ngc ngn (31 bp) v n m
ha cho transposase. Gene m ha cho transposase eukaryote cha 3
intron v 4 exon.
ng, yu t Ac v Ds c th di chuyn trn nhim sc th , tc ng
ln cc gene kim tra mu sc ca cc ht aleuron. Cc yu t ny c
phn lp cho thy c lin quan vi DNA transposon ca vi khun v ca
cc eukaryote khc. Ging vi yu t P ca rui dm, yu t Ac c on
cui lp li o ngc m ha cho transposase, yu t Ds li khng m
ha cho transposase. Khi Ac trn genome, transposase ca n c th bm
vo u mt ca c yu t Ac v Ds v khi ng s chuyn v ca
chng..
243
Yu t Ac v Ds l thnh vin ca h transposon n gin. Ngoi ra,

cn c cc h yu t di ng khc ng. Mi h cha yu t t ng m
ha cho transposase c th chuyn c yu t trong cng mt h, nhng
khng th chuyn n cc h khc v transposase ch c th bm vo u
mt ca cc thnh vin trong h.
ngi, yu t di ng chim mt na genome ngi. a s yu t
di ng thuc 2 dng retrotransposon l yu t nhn ri rc kch thc di
(long interspersed nuclear element) LINEs v yu t nhn ri rc kch
thc ngn (short interspersed nuclear element) SINEs. LINE di chuyn
nh retrotransposition s dng yu t m ha reverse transcriptase,
nhng li thiu mt vi tnh cht v cu trc ca yu t ging retrovirus
bao gm LTR.
SINE c m t nh l LINE khng t ng, v chng c tnh cht
cu trc c trng ca LINE nhng khng m ha cho reverse
transcriptase ring. Ngi ta cho rng chng di chuyn c nh enzyme
reverse transcriptase c m ha bi LINE trong genome.
SINE ngi c gi l trnh t Alu v n cha trnh t im ct
ca enzyme ct hn ch Alu. Genome ca ngi cha hn 1 triu trnh t
Alu ch mt phn hoc ton b, chim hn 10% genome ca ngi. Trnh
t Alu y c kch thc 200 nucleotide. DNA genome mang yu t di
ng ln hn 20 ln DNA m ha cho tt c protein ngi.
Tn s t bin ngu nhin do xen vo yu t nhm 2 l thp cha
n 0,2% trong tng cc t bin ngu nhin. Trong khi nhng t bo
ng vt khc nh chut do xen retrotransposon ln n 10% t bin
ngu nhin, cao hn 50 ln ngi c l lin quan vi hot tnh ca yu t
retrotransposon cao hn chut.
Cu hi v Bi tp
1. V sao phn ln cc t bin nh hng n cc gene cu trc
thng l ln so vi cc allele hoang di?
2. S hnh thnh t bin dch khung din ra nh th no?
3. Cc ha cht gy t bin c c im g?
4. Gii thch c s t bin ca cc tc nhn gy t bin sau: 5bromuracil, acid nitr v acridin. Xc nh xem chng to ra dng t bin
no (ng hon, o hon hay dch khung)?
5. Hy m t mt loi sai hng ngu nhin dn n t bin.
6. Phn tch s ging nhau v khc nhau gia cc kiu transposition.
244
7. Cc trnh t o ngc c vai tr g trong transposition?

8. Cho mt chui trnh t nucleotide trn mRNA nh sau:
Dng hoang di: ... 5' AAUCCUUACGGA 3' ...
Dng t bin: .... 5' AAUCCUACGGA 3' ...
Hy cho bit: Sai hng trn xy ra do loi t bin no?
9. t bin xy ra trong trnh t nucleotide do kt cp nhm nh sau:
5' AGCTGCCTT 3'
3' ACGATGGAA 5' (mch khun)
mRNA
Hy cho bit: Amino acid no s c tm thy codon c nucleotide
b thay i nh trn?
10. bp, tn s t bin ca locus R (mu cy) rt cao: 492 t bin
trn 106 giao t. Gene to mu ca ni nh Pr c tn s t bin l 11
t bin trn 106 giao t. Hy cho bit: Cn phi phn tch bao nhiu cy
mi tm c 1 t bin kp ca 2 gen trn?
Ti liu Tham kho

Ting Vit
Phm Thnh H. 2000. Di truyn hc. NXB Gio Dc.
L nh Lng, Phan C Nhn (1998). C s di truyn hc. NXB Gio
dc.
Hong Trng Phn. 1995. Di truyn hc phn t. Trung tm o to T
xa, i hc Hu
Ting Anh
Harlt D.L., Jones E.W. 1998. Genetics - Principle and analysis. Jone and
Bartlett Publshers, Toronto, Canada.
genetics. McGraw-Hill, Companies, Inc., United States of America.
Watson D.J, Baker T.A., Bell S.P., Gann A., Levine M., Losick R. 2004.
Molecular biology of the gene. Benjamin/Cummings, San Francisco, USA.
245
Chng 9
Di truyn T bo cht
I. S di truyn t bo cht
1. S di truyn ca cc gene lp th
Trong s th phn ca thc vt bc cao, mt t bo trng c kch
thc ln c nhiu t bo cht phi hp vi nhn ca ht phn khng c t
bo cht chung quanh. Do hp t nhn c phn ln t bo cht ca
t bo trng. Nu hai b m c thnh phn nguyn liu di truyn trong t
bo cht khc nhau th th h con s nhn c nhiu nguyn liu di
truyn trong t bo cht ca m. Do s xy ra s di truyn theo th h
m.
Hin tng di truyn l m c pht hin rt sm Mirabilis
jalapa (Correns, 1908), Pelargonium zonale (E.Bauner, 1909). Cc cy
c l m c th c nguyn cnh vi l trng khng c chlorophyll.
Th nghim: Tp giao gia cy Mirabilis jalapa c nhng cnh khm
trng xanh theo cc php lai nh sau:
- Th phn cho hoa trn cnh l trng bng ht phn ca hoa trn
cnh l xanh lc, cho th h con nhng cy ging c th m c l trng
khng c chlorophylle. Cc cy ny cht v khng c kh nng quang hp
- Tp giao hoa trn cnh l xanh lc bng ht phn ca hoa trn cnh
l trng, tt c th h con c l mu xanh lc bnh thng.
- Nu th phn cc hoa ca cnh l m bi phn hoa ca cy xanh
lc th i con c cc c th l trng, l m v l xanh lc.
- Nu th phn cho ha ca cnh l xanh lc vi phn hoa cy l m
th i con gm ton c th l xanh lc.
* Gii thch: Trong trng hp ny ngi ta thy nhng cht c s
hnh thnh lp th c trong t bo trng s hnh thnh tin lp th, sau
hnh thnh lc lp. Ht phn khng c cht c s hnh thnh lp th nn
ht phn khng th truyn lc lp c. S khc nhau gia con ci v b
m v mt hoc nhiu tnh trng khi tp giao thun nghch chng t c s
tham gia ca nguyn liu di truyn trong t bo cht. S di truyn theo
h m quy nh s th hin tnh trng ph thuc vo c th m.
thc vt Pelargonium zonale c trng hp di truyn theo dng
cha. Nu hoa ca cy l m c th phn ca cy l xanh lc th 30%
cy lai c l m, 70% l xanh lc. Khi lai hon i cha m th 70% cy
246
lai l m v 30% l xanh lc.

2. S di truyn ca cc gene ty th
2.1. c im di truyn ca cc gene ty th
Theo Mendel, khi tp giao nhng sinh vt lng bi th c s phn ly
tnh trng theo ng nh lut ca Mendel v nhng gene trong nhn u
nm trn nhim sc th v trong gim phn c phn chia cho cc giao t
cng vi nhim sc th. i vi nhng tnh trng trong t bo cht
khng c mt h thng phn chia no m nhn nn khng c s phn ly
theo mt quy lut nht nh.
nm men c mt th t bin c th hnh thnh nhng khun lc
petite kch thc nh hn bnh thng, ng knh ch bng 1/2 - 1/2
khun lc bnh thng. Cc t bo to nn khun lc petite c kch thc
ging kch thc t bo bnh thng. Nguyn nhn to nn khun lc kch
thc nh l do cc t bo t bin petite b hng h thng h hp, tc l
nhng enzyme oxy ha trong ty th l cc cytochrom b, c, a, a3 v
cytochrom oxydase b ph hy. y l nhng enzyme ca mng trong ty
th. Khc vi kiu di, cc t bin petite khng thc hin c phn ng
phosphoryl ha sn ra nng lng, v vy tc sinh trng v phn
bo ca chng thp hn.
ty th ca nm men (Saccharomyces cerevisiae) c 3 kiu t bin
ch yu: petite, antR v mit-.
Mt v d v ty th l t bin thiu nng h hp nm men. Vo
nhng nm 1940, Boris Ephrussi v cs. m t cc t bin c bit
nm men.Cc t bin ny c gi l petite, c khun lc nh hn nhiu
so vi khun lc hoang di. Theo phng thc di truyn, cc t bin
petite chia lm 3 loi khc nhau:
- Petite phn ly (Segregation petites): khi lai vi dng hoang di
khun lc bnh thng th t l phn ly trong cc nang bo t (ascospore)
l 1 khun lc to: 1 petite.
- Petite trung tnh (Neutral petites): khi lai vi khun lc to th s
phn ly trong nang bo t ch c dng khun lc to bnh thng, th hin
s di truyn theo mt cha m (Uniparental)
- Petite c ch (Suppressive petites): khi lai to cc nang bo t, mt
s mc thnh khun lc to bnh thng, mt s khc to khun lc petite.
T l gia khun lc to v nh dao ng nhng c tnh c hiu ca
chng, mt s petite c ch ch to th h con khun lc petite. Qua cc
petite c ch cho thy c s di truyn ngoi nhn t bo v mt s c s di
truyn theo mt cha m.
247
Khi lai nm men 2 t bo cha m, hai t bo cha m kt hp vi nhau

v gp t bo cht nh nhau vo t bo con lng bi. S di truyn ca
cc petite trung tnh v c ch c lp vi kiu bt cp th hin r s di
truyn ngoi nhn nn c gi l petite t bo cht. Qua nghin cu
chng c cc c im kiu hnh nh sau:
- Chui chuyn in t ca ty th b sai hng cc petite t bo cht.
Do sai hng ny, chng ln men to ATP km nn mc chm.
- Khng c sinh tng hp protein cc petite t bo cht. Cc ty th
c h thng sinh tng hp ring gm tRNA, cc ribosome khc vi t bo
cht.
- mtDNA cc t bin petite c bin i ln. Ty th ca tt c cc
Eukaryote c mtDNA ring tuy s lng nh, nhng khc vi DNA ca
nhn t bo. cc petite trung tnh, mtDNA b mt hon ton, cn cc
petite c ch c s thay i ng k t l base so vi mtDNA ca dng
khun lc to bnh thng.
Nhm cc t bin th hai ca nm men l antR (antR mutants), c
kiu hnh khng vi cc khng sinh khc nhau. V d: capR
(chloramphenicol resistance) khng chloramphenicol, eryR khng
erythromycine, spiR khng spiromycine, parR khng paranomycine v oliR
khng oligomycine. Cc t bin ny khi lai (v d eryR eryS) cho t l
phn ly khng theo quy lut Mendel, ging nh cc petite c ch nhng s
di truyn c khc. Khi cc t bo cha m kt hp, sn phm lng bi l
hp t hai cha m cytohet (cytoplasmically heterozygote). Cc diploid ny
c th sinh sn v tnh bng mc chi.Trong nguyn phn, qu trnh phn
ly t bo cht v ti t hp xy ra v cc t bo con tr thnh eryS hay
eryR.
Nhm t bin quan trng th ba l mit- (mit- mutants) c pht hin
sau cng nh k thut chn lc c bit. Cc t bin ny, tng t cc
t bin petite ch c khun lc nh v cc chc nng bt thng ca
chui chuyn in t, nhng im khc cn bn l sinh tng hp protein
bnh thng v c kh nng hi bin. Nh vy, cc kiu t bin mit- l
t bin im. S di truyn cu kiu t bin mit- ging vi kiu antR, c
s phn ly t bo cht v s di truyn theo mt cha m trong gim phn.
Trong th h con ca nhng t bo thuc khun lc bnh thng, c
khong vi phn trm t bo hnh thnh nhng khun lc petite. Nhng t
bo khun lc petite lun lun pht trin thnh nhng khun lc petite.
iu chng t c s thay i v cu trc di truyn. Ngoi t bin xy
ra kiu bo gene ni trn dn n sinh ra nhng khun lc petite, cn c
nhng khun lc petite do nhng gene trong nhn quy nh.
248
Th nghim: Tp giao ca mt ni nm men kch thc khun lc

bnh thng vi mt ni c kch thc khun lc petite, th h con hnh
thnh khun lc bnh thng. Cn i vi nhng gene trong nhn (gene
ade), th s phn ly th h con v nhng gene ny cho t l 1:1, do
chng nm trn NST v c chia u cho cc t bo con.
y, nguyn liu di truyn trong t bo s c trn ln nhau trong
hp t v khi to thnh bo t th mi bo t u nhn c cc gene
trong ty th nh nhau, nn chng u c chc nng h hp bnh thng.
Th nghim cho thy s di truyn khun lc khng theo quy lut
Mendel.
2.2. Hin tng bt dc bo cht c
Ging hu th
S to thnh ht phn
Cy bt th c,
ht phn mt
chc nng
Th h th ba ca
lai ngc vi
ging bt th c
T bo cht
c di truyn
theo dng m
Ht to thnh
do lai ngc
ln th nht
Ging bt th c
3/4 gene l
ca ging
hu
Ht to thnh
do lai ngc
ln th hai
Gene nhn l mt phc hp

allele ca b m, t b
hu th
7/8 gene l
ca ging
hu th c
Ht to
thnh do lai
ngc ln
th ba
Bt th c trong trng hp
ny l kt qu ca di truyn t
bo cht
Hnh 9.1 S th nghim chng minh s di truyn theo h m ca hin

tng bt th c.
Tnh bt dc do nhiu nguyn nhn, bt dc c (khng to phn hoa

hay to phn hoa khng c kh nng th tinh) thc vt c cc trng
hp sau:
- Do gene nhn quy nh, nh gene ms cy ng
- Do nh hng ca iu kin mi trng nh m, quang chiu,
249
kh nng cung cp cht dinh dng khng p ng ng nhu cu sinh l

ca cy
V d: gene ms cy ng
- Do lai xa cng a n cc c th lai khng c ht phn v NST c
ngun gc khc nhau khng th tip hp nhau trong gim phn. Nhng
hin tng bt dc ny u c ngha hn ch ch c bt dc bo cht c
l c vai tr quan trng. l trng hp bt dc ca ht phn bt ngun
t t bo cht, cn nhn th c th c iu chnh c nh c th dng
cc cy bt dc bo cht c pht huy u th lai cc i tng ng,
cao lng, c ci ng...
V d: Xt mi quan h gia kiu gene, kiu bo gene v kiu hnh
ca bp c s dng trong lai mt tnh m khng cn kh c cy m
STT
1
2
3
4
Kiu gene
Rfrf
Rfrf
RfRf hoc Rfrf
RfRf hoc Rfrf
kiu bo gene
S (bt dc)
N (hu dc)
N
S
kiu hnh (ht phn)

hng
tt
tt
tt
Vy ht phn ca ng ch b mt hot tnh khi c yu t bt dc trong

t bo cht m li thiu thiu gene phc hi hu dc (Rf) trong nhn,
alen ca gene ny l rf l gene cng c tnh bt dc.
Cy c phc hi hu dc RfrfS cho t th phn th i sau s c
1/4 rfrf c ht phn hng. Nu ly bp ca dng rfrfS th phn ca rfrfN,
th phn hoa ca ton b i sau s b hng, cy ny ch cn bp mang nh
ci. l cch dng phng php di truyn kh c ng. Khi sn xut
ht ging, nhng cy ny mun c ht th phi th phn hu dc ca
nhng cy bnh thng. Nu mun dng nhng ht sau ny trng li
th cy b phi c kiu gene RfRf v kiu bo gene N hoc S.
Trong sn xut ging ng c th dng t hp dng thun dng 1 lm
cy m v dng 3 hoc dng 4 ng hp t lm cy b. Nh th s mt
cng kh c cy m v ht lai thu c t cy m s c kiu gene Rfrf,
kiu bo gene S. Kiu gene ny m bo c s th phn bnh thng
lc trng trong sn xut.
Bt th c t bo cht ng lin quan n 2 plasmid dng thng S1
v S2. Chng trong ty th cng vi mtADN. Mt trong nhng tnh cht
kh hiu ca plasmid ny l chng c th thc hin ti t hp vi mtADN.
3. Hiu qu dng m ln chiu xon v c
Trng v phi chu nh hng ca mi trng c th m nhiu hn
250
c th b. Ngay c khi b tch khi c th m t mt giai on rt sm,

chng cng nhn c t bo cht, cc cht dinh dng trong trng t
m v nhng nh hng c bit ln hot ng ca gene. Nhng tim
nng nht nh ca trng c xc nh trc khi th tinh v trong mt s
trng hp chng chu nh hng ca mi trng m bao quanh. S
quyt nh trc nh vy do cc gene ca m hn l cc gene ca con,
c gi l hiu ng m. S tn ti ca hiu ng m ni chung c
chng minh bng phng php lai thun nghch, khi kt qu php lai
thun nghch s khc nhau.
V d v hiu qu dng m: chiu xon ca v c Limnaea peregra.
Chiu xon ny c xc nh bi mt cp alen. D l xon phi, d l xon
tri. Cc php lai cho thy D l tri so vi d v chiu xon lun lun c
xc nh bi kiu gene ca m.
Th h P
Xon phi
Xon tri
Xon tri
Xon phi
T phi
T phi
Th h F3: 3 xon phi :

1 xon tri
Th h F3: 3 xon phi :

1 xon tri
Hnh 9.2 Hiu qu dng m ln chiu xon v c
Tin hnh php lai thun nghch gia ng hp t DD xon phi v

ng hp t dd xon tri:
Khi trng bt ngun t c xon phi th F1 l Dd v kiu gene v c
c kiu hnh xon phi. Cho cc con c ny t phi th sinh ra th h sau
c t l phn li v kiu gene l 1DD : 2 Dd : 1 dd, tt c cc con c thm
251
ch c con c kiu gene dd u c chiu xon phi. Nhng khi mi con c

ca th h ny t phi ring bit th ch c nhng con c kiu gene DD v
Dd cho th h sau xon phi, cn nhng con dd mc d c kiu hnh xon
phi nhng li cho th h sau xon tri.
Ngc li nu dng c dd xon tri lm m th F1 Dd u xon tri
ging m. Cho cc c con ny t phi th tt c c th h sau c xon phi
v kiu gene ca m chng l Dd. Nu cho mi con ca th h ny t phi
th kt qu nhn c nh php lai thun trn, ngha l th h sau c t l
phn ly 3 xon phi : 1 xon tri.
Nh vy hiu qu dng m ch ko di mt th h v trng hp ny
khng th xem l di truyn qua t bo cht bi v y cc c tnh ca t
bo cht c xc nh trc bi tc dng ca cc gene trong nhn ch
khng phi bi cc gene trong t bo cht. Ni cch khc y c ch di
truyn nhim sc th lm bin i t bo cht ca trng trc khi n th
tinh.
II. Lp bn ty th v lp th
1. Lp bn gene ca DNA lp th
Cc gene ca lc lp Chlamydomonas reinhardii
S di truyn lc lp c nghin cu chi tit hn c vi to
Chlamydomonas reinhardii. T bo ca vi to ny c mt lc lp ln vi
ng knh trung bnh 5 m cha 50 n 80 bn sao ca phn t DNA
vng trn di 196 kb.
Theo Sager (1975), Chlamydomonas reinhardii c cc t bin
trong nhm lin kt gene ca lc lp. Cc t bin c biu hin kiu hnh
nh sau:
- Mt kh nng quang hp mc c ngoi nh sng v trong ti
cn b sung ng kh l acetat
- Nhy cm vi nhit cao hoc thp
- Tnh khng vi thuc khng sinh hoc c nhu cu c cung cp
thuc khng sinh.
Tt c cc t bin trn c s di truyn theo mt cha m, c kiu bt
cp mt+ (c th coi l dng m). iu ny lin quan n s hnh thnh lc
lp trong hp t, bng cch no , ch nhn DNA t lc lp mt+.
Nm 1954, R. Sager nghin cu cc t bin khng streptomycin
C. reinhardii t dng hoang di nhy cm sm-s. Mt s t bin sm-r c
s di truyn nhim sc th vi s phn ly 1 : 1. Tuy nhin mt s t bin
c s di truyn khc thng nh sau:
252
sm-r mt+ sm-s mt- tt c i con u sm-r vi t l 1 mt+ : 1 mt-.

sm-s mt+ sm-r mt- tt c i con u sm-s vi t l 1 mt+ : 1 mt-
Hnh 9.3 Bn vng trn ca cpDNA Chlamydomonas
Hnh 9.4 Bn DNA chloroplast ca Marchantia polymorpha

IRA v IRB l nhng trnh t o ngc (theo K.Umesono v H.Ozeki, 1987)
B
Nh vy y khi c s hon i cha m trong lai, th h con u c kiu

hnh streptomycin ca mt+. S truyn th tnh trng ny c gi l s di
truyn theo mt cha m. Sager coi mt+ nh dng m v trng hp trn
ging nh di truyn theo dng m. Cc kiu bt cp mt c t l phn ly
ca gene trong nhn l 1 : 1.
Trong t hp lai mt+ sm-r mt- sm-s c khong 0,1% th h hp t
con mang c sm-r v sm-s. Cc hp t nh vy gi l hp t hai cha m
cytohet (cytoplasmically heterozygote).
253
Tn s cc cytohet c th tng ln 40-100% th h hp t con nu

mt+ c chiu tia t ngoi trc khi lai.
Chlamydomonas, cc hp t 2 cha m c dng lm im xut
pht cho tt c cc nghin cu v s phn ly v ti t hp ca cc gene lc
lp.
Trn c s nhiu t hp lai, R. Sager nu ra bn vng trn ca
cpDNA vi cc gene tng ng.
2. Lp bn gene ca DNA ty th
* Lp bn b gene ty th ca nm men
C c c phng php khc nhau xy dng bn b gene ty th:
- Lp bn ti t hp (recombination mapping): nm men s
phn li t bo cht v ti t hp xy ra trong qu trnh mc chi cytohet
lng bi. S phn li v ti t hp c th pht hin trc tip cc dng
lng bi mc chi hay quan st sn phm gim phn khi chi c kch
thch to bo t.
V d khi lai eryRspiR erySspS c th nhn c cc kiu b bn vi
s lng nh sau:
eryRspiR
63 b bn
S
S
ery spi
48 b bn
S
R
ery spi
7 b bn
R
S
1 b bn
ery spi
S
R
Cc kiu gene ery spi v eryRspiS l cc dng ti t hp.
- Lp bn bng phn tch petite: Mt s k thut lp bn c hiu
qu da trn s phi hp c 3 loi t bin petite, antR v mit-. Phn ln
cc tip cn ny da vo s mt on ca mtDNA ca cc t bin petite.
S kt hp cc kiu phn tch di truyn c bit vi k thut ti t hp
DNA dn n xy dng bn di truyn hon chnh ca mtDNA.
- Lp bn bng phn tch enzyme ct gii hn: cc enzyme ct gii
hn (xem chng 10) l cng c hu hiu mi phn tch di truyn. N
c s dng khng nhng phn tch mtDNA ca nm men, m c
mtDNA ca bt k sinh vt no min chit tch v tinh sch c DNA.
* Bn mtDNA ca nm men v ngi
Vic xy dng bn mtDNA hon chnh ca nm men v ngi l
nhng thnh tu ng k ca nghin cu di truyn t bo cht.
- Mt s trnh t c codon khi s v codon kt thc cui nhng
cha bit chc nng
254
- mtDNA ca ngi rt t d tha

Phin m ca si nh
Phin m ca si nng
Nhng trnh t
n m ha cho
amino acid trn
tRNA
mtDNA ca ngi
Kt qu t bin
tRNALys vng
MERRF
Hnh 9.5 Bn mtDNA ca ngi (Theo Larson v Clayton, 1995)
III. Di truyn hc phn t cc bo quan

1. Cc b gene lp th (cpDNA)
L bo quan c kh nng t ti sinh t bo thc vt. S phn chia
ca cc bo quan ny v v cc t bo con trong phn bo l khng u
nh s phn chia ca nhim sc th trong nguyn phn v gim phn.
Chng c s lng ln v phn chia ngu nhin v cc t bo con nn mi
t bo c th cha nhiu hoc t lc lp.
DNA ca lc lp c k hiu l cpDNA (Chloroplast DNA). B
gene ny dng DNA vng trn, thng di hn DNA ca ty th 8-9 ln.
Trong lc lp cn tm thy b my sinh tng hp protein khc rt nhiu
vi h thng trong t bo cht ca eukaryote nhng ging vi b my sinh
tng hp protein ca prokaryote.
Mc d s di truyn ca lc lp c pht hin rt sm, nhng trong
mt thi gian di s hiu bit chi tit v cc gene ca lc lp khng c
bc tin ng k. Cc nghin cu phn t gp phn ch yu cho s
phn tch chi tit cc gene cc bo quan. Ngoi cc nghin cu
Mirabilis jalapa v Chlamydomonas, bn chi tit cpDNA ca thc vt
Marchantia polymorpha c xy dng.
255
cpADN in hnh di khong 120-200 kb ty loi thc vt.

Marchantia, kch thc phn t l 121 kb.
Trn cpDNA ca Marchantia c tt c 136 gene gm 4 loi m ha
tng hp rRNA, 31 loi m ha tng hp tRNA v khong 90 gene tng
hp protein. Trong s 90 gene m ha tng hp protein, c 20 gene m
ha tng hp enzyme cho quang hp v chui chuyn in t. Cc gene
m ha cho cc chc nng dch m chim khong mt na b gene ca lc
lp v bao gm cc protein v cc RNA cn thit cho dch m bn trong
lc lp.
Thc t DNA ca lc lp, ty th v nhn t bo c s phi hp cht
ch trong vic to ra cc tiu phn ca nhng protein c s dng bn
trong lc lp. Ribulose-1,5-biphosphate carboxylase/ oxygenase l enzyme
di do nht ca lc lp. N xc tc 2 phn ng cnh tranh nhau, c nh
CO2 v bc u tin ca quang h hp (photorespiration) vi s to ra
glycolate. Enzyme gm 8 tiu phn ln LS (large unit) ging nhau v 8
tiu phn nh ging nhau c m ha tng ng bi cc gene ca lc lp
v nhn t bo. Tiu phn ln LS mang trung tm xc tc, cn vai tr ca
cc tiu phn nh cha r. Gene LS nm trn cpDNA ca mt s thc vt
nh bp, Chlamydomonas reinhardii, thuc l, Euglena... Trong tt c cc
trng hp, gene LS hin din 1 bn sao cho 1 DNA ca lc lp. Ngc
li, cc gene ca tiu phn nh c tm thy cc trnh t DNA ca nhn
t bo vi s bn sao t.
2. Cc b gene ty th (mtDNA)
Bo quan ty th c tt c cc t bo ca eukaryote. B gene ca ty
th c k hiu l mtDNA (Mitochodrial DNA). mtDNA m ha cho s
tng hp nhiu thnh phn ca ty th nh h thng 2 loi rRNA, 22-25
loi tRNA v nhiu loi protein c trong thnh phn mng bn trong ty
th. Trong khi , phn ln protein ca ribosom ca ty th th do cc gene
trong nhn xc nh.
B gene ca ty th c hai chc nng ch yu:
- M ha cho mt s protein tham gia chui chuyn in t
- M ha cho h thng sinh tng hp protein gm mt s protein, tt
c cc tRNA v c 2 loi rRNA.
Tuy nhin trong c hai trng hp, nhng cu phn cn li ca h
thng c m ha do cc gene nhn v c dch m bo tng
(cytosol) ri chuyn vo ty th.
Vit Nam c cng trnh phn tch mtDNA 50 ngi Vit dn
tc Kinh, pht hin c cc hnh thi khc nhau khi ct mtDNA bng 6
256
enzyme hn ch.
Nh vy, vic nghin cu cc gene ca ty th cho thy t bo
eukaryote khng lc lp c t nht 2 h thng sinh tng hp protein c
lp tng i nhng lun hp tc cht ch vi nhau. cc eukaryote c
lc lp th 3 h thng sinh tng hp protein c lp tng i nhng hp
tc vi nhau. C 2 bo quan ty th v lc lp tham gia trc tip vo chuyn
ha nng lng ca t bo.
Di truyn t bo cht l hin tng di truyn do cc gene nm trn
nhim sc th ngoi nhn quy nh.
Cu hi v Bi tp
1. Hy nu cc kiu t bin ca ty th.
2. Trnh by chng minh thc nghim v di truyn lp th.
3. So snh s ging nhau v khc nhau ca mtDNA v cpDNA.
4. Nu c ht bp t dng bt thu c, lm sao xc nh s bt th do
gene trong nhn hay ngoi nhn?
5. Nu cc c im ring ca di truyn ngoi nhim sc th v nu
cc sai khc c bn so vi di truyn ca gene nhn.
6. Hy phn bit hiu qu dng m vi s di truyn ngoi nhn.
7. Hy phn bit cc loi t bin petite nm men.
8. Cho 2 dng bp bt dc c: mt dng bt dc bo cht, mt dng
bt dc do gene nhn di truyn theo Mendel. Hy trnh by phng php
xc nh hai dng bt dc trn.
9. Mt con c loi Limnaea peregra c v xon tri qua t phi cho
tt c th h sau xon phi. Hy xc nh genotype ca con c ny. Nu
th h sau cho t phi ring r, hi chiu xon v ca cc con c th h
ny nh th no?
10. T l tin ha DNA ca ty th c tnh bng s bin i 1
nucleotide ca 1 ty th trong thi gian 1.500 n 3.000 nm. DNA ty th
ngi c khong 16.500 nucleotide. Hi t l bin i ca 1 nucleotide
trong 106 nm l bao nhiu?
Ti liu Tham kho

Ting Vit
Phm Thnh H. 2000. Di truyn hc. NXB Gio Dc.
257
L nh Lng, Phan C Nhn. 1998. C s di truyn hc. NXB Gio

dc.
Phan C Nhn, Nguyn Minh Cng, ng Hu Lanh. 1999. Di truyn
hc. NXB Gio dc
Hong Trng Phn. 1995. Di truyn hc phn t. Trung tm o to T
xa, i hc Hu
Ting Anh
Harlt D.L., Jones E.W. 1998. Genetics - Principle and analysis. Jone and
Bartlett Publshers, Toronto, Canada.
genetics. McGraw-Hill, Companies, Inc., United States of America.
Vu Trieu An. 1999. Mitochondrial DNA Polymorphism in the Vietnamese
population. Eur. J. of Immunogenetics, 26: 471- 422.
Watson D.J, Baker T.A., Bell S.P., Gann A., Levine M., Losick R. 2004.
Molecular biology of the gene. Benjamin Cummings, San Francisco,
United States of America.
258
Chng 10
i cng v Cng ngh DNA Ti t hp

Vic tinh ch enzyme ct gii hn u tin (1970) v s dng n
to ra cc phn t DNA ti t hp u tin trong ng nghim (1972-1973)
l nn tng cho s ra i ca k thut di truyn (genetic engineering) v
cng ngh DNA ti t hp (recombinant DNA technology). Chnh s pht
trin nhanh chng ca lnh vc ny khng nhng a li khi lng tri
thc khng l v cu trc v c ch hot ng ca cc gene, cc b gene
prokaryote v eukaryote m cn tr thnh lc lng sn xut trc tip ca
x hi: to ra hng lot cc ch phm y-sinh hc hu ch t cc t bo vi
khun, nm men; to cc ging sinh vt mi... gp phn gii quyt nhng
vn thc tin t ra trong y hc v trong cng tc chn to ging.
Trong chng ny chng ta s tm hiu cc c tnh ca enzyme ct
gii hn, cc nguyn l c bn ca k thut DNA ti t hp v mt s ng
dng ca lnh vc cng ngh ny.
I. Cc cng c chnh ca k thut to dng DNA ti t hp

1. Cc enzyme ct gii hn
1.1. Enzyme ct gii hn l g?
Enzyme ct gii hn (restriction endonuclease) hay gi tt l enzyme
gii hn (restrictase) l loi enzyme c kh nng nhn bit on trnh t
nucleotide c hiu trn cc phn t DNA v ct c hai si DNA b sung
ti cc v tr c th.
1.2. Vai tr ca cc enzyme ct gii hn
T 1953 ngi ta pht hin thy rng, khi a DNA ca mt ni vi
khun E. coli ny vo t bo thuc mt ni khc thng th DNA c
a vo, gi l DNA ngoi lai hay DNA l, mt hn hot tnh di truyn v
hu nh bao gi cng b phn ct thnh cc on ngn. Ch trong mt s t
trng hp DNA l mi khng b phn ct v do n c th ti bn
trong t bo ch. iu chng t DNA l c sa i bng cch no
di s kim sot ca t bo ch. Cc hin tng ni trn xy ra ch yu
khi cc th thc khun (phage) xm nhim cc t bo vi khun.
Cho n u thp nin 1970 ngi ta mi bit r rng cc t bo vi
khun l nhng h thng cha c hai loi enzyme: cc enzyme sa i v
cc enzyme ct gii hn. Chng u c i tng nhn bit l cc on
trnh t ca DNA vt ch v DNA ngoi lai, nhng c vai tr khc nhau.
C th, cc enzyme sa i (methylase) ng vai tr bo v DNA vt ch
259
bng cch gn thm nhm methyl (-CH3) mt s base nht nh trong

on nhn bit (recognition sequence) hay on ch (target sequence).
Hin tng methyl ho (methylation) ny thng xy ra i vi adenine
v bin i n thnh N-6 methyladenine. Trong khi , cc enzyme gii
hn li ng vai tr v hiu ho hot tnh di truyn ca cc DNA l bng
cch phn ct cc v tr c th chng no n cha c sa i cho
ging vi DNA vt ch. Nh vy, cc enzyme gii hn ng vai tr l
hng ro bo v t nhin ca cc vi khun nhm chng li s xm nhp
ca cc phage l.
1.3. Tnh cht chung ca cc enzyme gii hn
Trc tin, cn lu rng cc enzyme gii hn ch pht hin thy cc
vi khun m khng c cc eukaryote. V vy, tn gi ca cc enzyme
gii hn thng dng l tn h thng, c biu th bng ba hoc bn ch
ci vit tt ca vi khun m t enzyme c chit xut. Ch ci u
tin c vit hoa ch chi (genus) v hai ch ci tip theo vit thng
ch loi (species), v khi cn thit thm ch ci th t ch ni hoc
chng (strain, type). Ngoi ra, phn bit cc enzyme cng mt ni
ngi ta dng s La M km theo sau tn h thng (xem bng 10.1).
cc on DNA ni
cc u dnh
u dnh
u dnh
+ DNA ligase
DNA ti t hp
Hnh 10.1 Enzyme gii hn (EcoRI) ct cc DNA khc nhau, nh c th

kin to phn t DNA ti t hp in vitro (bng enzyme DNA ligase).
Tnh cht quan trng nht ca cc enzyme gii hn l tnh c hiu v

tr, ngha l chng c th nhn bit on trnh t DNA c th ct v
tr xc nh. Tu theo v tr ct so vi on nhn bit m chia ra hai loi:
260
loi I bao gm cc enzyme gii hn ct bn ngoi phm vi on nhn bit

v loi II bao gm cc enzyme ct c hiu bn trong on nhn bit.
y chng ta ch xt cc enzyme gii hn loi II vn c xem l cng c
hiu nng (ging nh con dao m tinh vi) cho php thao tc trn cc gene
trong k thut DNA ti t hp (hnh 10.1).
c trng ni bt ca cc on ch l c kch thc ngn, 4-8 cp
base, v c tnh i xng xui ngc (palindrome).
Nhn chung, cc enzyme gii hn khc nhau c hai kiu ct sau y:
ct lch v ct thng. Vi kiu ct lch tc l cc v tr ct trn hai si ca
DNA si kp l so le, to ra cc on DNA c cc u si n gm mt s
base b sung gi l cc u dnh (cohesive/sticky ends). Cc enzyme gii
hn nh th c vai tr to ln trong vic kin to DNA ti t hp in vitro
(hnh 10.1). in hnh y l EcoRI v BamHI (bng 10.1). Vi kiu ct
thng, tc ct cng v tr trn c hai si ca DNA si kp, do to ra cc
on DNA c cc u bng (blunt ends); v d, SmaI...(bng 10.1).
Cc enzyme gii hn khc nhau c on ch ging nhau, mc d v tr
v kiu ct c th ging hoc khc nhau, gi l cc enzyme gii hn tng
ng (isoschizomers); v d, SmaI v XmaI (bng 10.1).
Bng 10.1 Cc trnh t nhn bit v v tr ct ca cc enzyme gii hn c
chn lc (mi tn ch v tr ct; cc trnh t y c ch ra trn si 5'3')
Ngun vi sinh vt
Arthrobacter luteus
Bacillus amyloliquefaciens H
Escherichia coli RY13
Haemophilus influenzae Rd
Haemophilus influenzae Rd
Nocardia otitidis-caviarum
Providencia stuartii
Serratia marcescens Sb
Xanthomonas malvaccarum
Tn enzyme
AluI
BamHI
EcoRI
HindII
HindIII
NotI
PstI
SmaI
XmaI
Trnh t nhn bit

AGCT
GGATCC
GAATTC
GTPyPuAC
AAGCTT
GCGGCCGC
CTGCAG
CCCGGG
CCCGGG
2. Cc vector thng dng trong k thut di truyn

2.1. DNA ti t hp l g?
DNA ti t hp (recombinant DNA) l phn t DNA c to ra trong
ng nghim bng cch kt hp cc DNA t cc ngun (loi) khc nhau,
theo mt quy trnh k thut nht nh, gi l k thut ti t hp DNA.
Thng thng mt phn t DNA ti t hp bao gm mt phn t DNA
c bn cht l plasmid hoc phage nguyn vn gi l vector (th ti) v
mt on DNA t ngun khc mang mt gene hoc yu t iu ha mong
261
mun c cho xen vo; n c gi l DNA ngoi lai (foreign DNA).

2.2. Hai loi vector thng dng
Vector l phn t DNA c kch thc b hoc va phi, ng vai tr l
vt trung gian mang truyn on DNA ngoi lai nghin cu vo trong t
bo th nhn (t bo kh bin) bng con ng bin np (transformation)
hoc ti np (transduction).
C hai loa vector thng dng l cc plasmid hoc cc phage. Cc
plasmid vi khun (hnh 10.2) c s dng rng ri hn c, bi v chng
c cc c im sau: (i) c kh nng xm nhp vo t bo vt ch m vn
hot ng (ti bn, biu hin gene) bnh thng; (ii) c trng lng phn
t thp nn d dng tinh chit; (iii) s bn sao trong mi t bo vi khun
thng kh cao; v (iv) c bit l, mt s plasmid c cha cc gene
khng thuc tin li cho vic theo di v pht hin s c mt ca plasmid
ti t hp trong vi khun ch.
cc khi im ti bn
Hnh 10.2 Cc plasmid c cha khi im ti bn (ori), cc im ct ca

mt s retrictase v cc gene khng ampicillin (AmpR), kanamycin (KanR).
Trong s cc phage dng lm vector th phage lambda () c nhiu

u th nht, bi l phn gia ca b gene c cha mt s gene khng
quan trng v khng lin quan vi s ti bn ca n, nn thun li cho
vic xen on DNA mong mun vo y. Cc phage khng cha cc gene
khng thuc cho nn vic theo di phage ti t hp c xc nh da vo
cc vt tan dng tnh (positive plaques) trn nn vi khun.
3. Thit lp phn t DNA ti t hp in vitro
262
3.1. Phng php s dng cc u dnh

Bt k on DNA no nu c ct bi cng mt loi enzyme gii
hn (v d, EcoRI) cho cc u dnh th c th dnh lp li vi nhau v
c ni bi DNA ligase (hnh 10.3). Phng php thnh lp phn t
DNA ti t hp kiu ny ln u tin c a ra bi J.Mert v R.Davis
nm 1972 bng thc nghim trn cc virus. V sau , ln u tin nm
1973, H.Boyer v nhm nghin cu ca S.Cohen to ra c phn t
DNA ti t hp gm vector l plasmid nh pSC101 ca E. coli v DNA
''ngoi lai'' l mt plasmid khc. Chnh s kin ny t nn mng v m
ra trin vng to ln cho k thut DNA ti t hp sau ny.
DNA s c
xen vo
DNA c ct
vi EcoRI
Cc u dnh
Ti t hp DNA
+ DNA ligase
Ni sai
DNA
ti t hp
Ni sai
Hnh 10.3 Hai phn t DNA khc nhau c ct bi cng mt enzyme gii
hn th c th ni vi nhau nh xc tc cu DNA ligase.
3.2. Phng php ni trc tip hoc tng hp cc u b sung

i vi cc on DNA c to ra bng cch x l enzyme gii hn
ct thng nh HindII chng hn, th vic ni cc on DNA c u bng
c to ra c th thc hin theo hai cch sau: Ni trc tip bng DNA
ligase ca phage T4 hoc tng hp thm cc u dnh vo cc u 3' mt
s nucleotide b sung bng cch s dng cc enzyme end transferase, ri
sau cc on DNA nh th s c ni vi nhau bi DNA ligase ca vi
khun. C s ca phng php kt hp DNA ny c thc hin ln u
tin gia DNA ca virus SV40 vi DNA ca phage bi L.Lobban v
263
D.Kaiser (1972), v D.Jackson v P.Berg (1972)
II. To dng gene hay DNA ti t hp

1. Nguyn tc chung
V nguyn tc, k thut DNA ti t hp hay to dng (cloning) gm
cc bc chung nht nh sau: (1) Tch chit v tinh sch DNA thuc cc
ngun khc nhau (gm vector v DNA mang gene mong mun); (2) to ra
phn t DNA ti t hp in vitro; (3) a phn t DNA ti t hp vo trong
t bo nhn, thng l E. coli hoc nm men. Hnh 10.4 m t mt quy
trnh k thut n gin nh th. Tuy nhin, trn thc t, s phc tp l
bc (4), pht hin v phn lp cc dng DNA ti t hp c hiu.
DNA ngoi lai
Cc on ct bi enzyme gii hn
Enzyme gii hn
Ni cc u dnh
Plasmid
ti t hp
Bin np
T bo ch
E. coli
T bo c bin np
Hnh 10.4 Mt quy trnh bin np DNA ti t hp vi vector l plasmid,

enzyme gii hn EcoRI, enzyme ni - DNA ligase, v t bo nhn l E. coli.
Trong t bo ch, phn t DNA ti t hp c th biu hin gene mong

mun (cho sn phm protein) hoc ti bn c lp nhiu ln to ra hng
lot bn sao ca n, v khi t bo ch phn chia s ko theo s to dng
phn t (molecular cloning). Mt khc, do tc phn chia rt nhanh ca
cc vi khun nn c th to hng triu bn sao mong mun trong mt thi
gian ngn. V th nh khoa hc c th tch dng bt k mt gene no
264
dng cho nghin cu hoc cho sn xut trn quy m cng nghip mt s
lng ln cc protein vn l nhng ch phm y-sinh hc no .
2. Quy trnh to dng gene ti t hp
By gi ta xt mt quy trnh k thut to dng m vic pht hin DNA
ti t hp da trn kh nng khng thuc do vector plasmid mang li.
Bc 1: Tinh chit DNA
Gi s tinh chit c plasmid c cha hai gene khng ampicillin
v tetracyclin, k hiu l AmpR v TetR; v cng gi thit rng gene TetR
c cha im ct ca EcoRI, v phn t DNA ngi c mang gene insulin.
Bc 2: Kin to phn t DNA ti t hp in vitro
Trc tin, dng enzyme gii hn u dnh EcoRI (xem bng 10.1)
ct vng plasmid ti gia gene TetR v cho ct DNA ngi, trong s cc
on b ct c mt on mang gene insulin. Sau em trn ln hai loi
DNA trn trong ng nghim vi DNA ligase. Kt qu l c th xy ra ba
trng hp: (1) Plasmid t ni li thnh mch vng nh lc u; (2) on
DNA t ni li thnh mch vng; v (3) Plasmid ti t hp c mang gene
insulin, v c th mang mt on DNA khng phi gene .
Bc 3: Bin np v pht hin dng DNA ti t hp chung
a cc DNA c x l vo cc t bo E. coli. Nu phn t c kch
thc ln ngi ta phi x l vi khun 'th nhn' bng chlorid calcium
(CaCl2) lm cho mng tr nn thm c d dng. Sau em cy
ring r cc vi khun trn mi trng c ampicillin v theo di.
+ Nu c xut hin khun lc (cc vi khun trong cng mt khun lc
th thuc mt dng v chng bt ngun t mt vi khun ban u), chng t
vi khun c mang gene AmpR, tc l chng c mang plasmid ban u
(trng hp 1) hoc plasmid ti t hp (trng hp 3). Ngc li, nu ch
cy khng xut hin khun lc, chng t vi khun mang DNA t ni
(trng hp 2).
+ K , em cy ring r cc vi khun thu c sang mi trng c
tetracyclin. Nu c xut hin khun lc, chng t vi khun c mang gene
TetR nguyn vn (trng hp 1). Nu khng c khun lc, chng t vi
khun em cy c mang DNA ti t hp (trng hp 3); v gene TetR b
bt hot do on DNA xen vo. Bng cch theo di nh vy cho php xc
nh c dng vi khun mang DNA ti t hp, nhng vn cha bit c
u l cc dng c hiu, ngha l c mang gene insulin.
Hnh 10.5 di y m t mt quy trnh n gin v to dng vi khun
mang gene insulin ngi.
265
DNA ngi
gene TetR
gene insulin
gene
AmpR
cc u dnh
Lai ho
+ DNA ligase
Bin np
T bo
vi khun
t cc vi khun ln mi trng
c b sung ampicillin
NST
vi khun
To dng
Nui cy
Dng
Ch c cc vi khun cha DNA

ti t hp sinh trng c
Tinh chit
DNA
Hnh 10.5 S th nghim to dng vi khun mang DNA ti t hp,

y l gene insulin ngi.
Bc 4: Chn dng DNA ti t hp c hiu

V nguyn tc, trong c triu php th mi c mt t bo mang gene
mong mun. Vi trng hp trn y chng hn, ngi ta c th s dng
phng php min dch hc bng cch dng khng th chng li protein
c sinh ra bi dng vi khun tng ng (tc huyt thanh tm gene
khng insulin). Ni chung, tm dng lai c hiu ngi ta s dng cc
mu d l mRNA hoc rRNA c hiu. Chng hn, trong trng hp nu
cn chn dng lai mang on mRNA c th, ngi ta em cy u cc
dng vi khun c cha DNA ti t hp ln trn mt thch ca hp petri
cha mi trng nui cy. Sau ng du ln mng lc nitrocellulose,
v thu c bn sao. Vic x l bn sao bng NaOH s lm cho cc t bo
vi khun tan v ti ch (in situ), v cc DNA thot ra t chng s b bin
tnh (cc si n tch ri nhau) v dnh vo mng lc. Sau em nhng
266
mng lc ny vo mu mRNA tng ng c tinh khit v nh du

phng x (P32); mu RNA ny c gi l vt d phng x (radioactive
probe). Nu dng no c cha DNA m ho cho mRNA th s xy ra hin
tng lai gia mRNA v vng si n tng ng trn DNA . Sau khi
loi b cc mRNA khng lai c, ngi ta t mt ming phim nh ln
trn mng lc; nhng vt nh xut hin trn nh phng x t ghi cho thy
v tr ca dng mang DNA b tr vi mu RNA. T y c th tch ring
cc dng lai c hiu s dng cho cc nghin cu tip theo.
Sinh trng qua m
T bo
+ pUC19
T bo + pUC19 T bo khng
+ on xen
c bin np
(a)
Cc khun lc xanh:
ch c pUC19
Cc khun lc trng:
pUC19 + on xen
Mi trng
+
ampicillin
+
X-gal
Mng
Cc dng khng ampicillin

Vt d
phng x
(b)
Cc dng chn lc
Mng
Phim tia X
(c)
Hnh 10.6 Xc nh cc dng vi khun mang plasmid c xen mt on
DNA (gene) c hiu bng vt d phng x l mRNA - sn phm ca n.
Hnh 10.6 minh ha mt cng on ca quy trnh th nghim DNA ti

t hp vi khun E. coli khi s dng mi trng nui cy c b sung
ampicillin i vi ba kiu t bo: t bo c mang plasmid ti t hp, t bo
ch mang plasmid pUC19 khng ti t hp, v t bo khng bin np c
(hnh 10.6a). Qua m sinh trng, cc t bo no c mang plasmid ti t
hp v plasmid khng ti t hp s mc thnh cc khun lc (mu sc
tng ng y l trng v xanh; hnh 10.6b). Sau khi chn ra cc dng
c xen plasmid ti t hp, a ln mng lc v cho tin hnh lai ha gia
RNA v DNA (gene) ca n bng cc vt d phng x nh ni trn.
Sau a sn phm lai phn t ny ln tm phim X quang nh v
267
gene quan tm t dng ti t hp (hnh 10.6c).

3. Tng hp v to dng cDNA
i vi trng hp cn cho biu hin mt gene l (sn xut mt
protein) mong mun trong vi khun, ngi ta c th tng hp gene ca n
da trn khun mu mRNA v enzyme phin m ngc tinh ch t cc
virus RNA (xem chng 5). Sau cho xen gene ny vo plasmid, ri
em cy vo vi khun v xc nh cc dng cDNA c hiu. y ta ch
xt hai bc u:
Bc 1: Tng hp cDNA
Nh bit, cc mRNA eukaryote u c ci ui poly(A) u 3'.
Chnh trnh t ny to iu kin thun li cho vic tng hp si DNA b
sung, cDNA. Khi em trn ln cc on ngn gm cc nucleotide thymine
(oligodT) vi mRNA ny s xy ra s lai ho gia n vi vng ui
mRNA. on oligo(dT) lm mi cho enzyme phin m ngc (reverse
transcriptase) tng hp si cDNA m sn phm l si kp lai RNAcDNA. u 3' ca si cDNA c tng hp c ci 'chp' (tng t u
5' ca mRNA). Tip theo, bng cch x l vi NaOH, si mRNA b loi
ra; k ci 'chp' u 3' ca cDNA li lm mi cho DNA polymerase I
tng hp si th hai dc theo si khun vn c ca n. Sn phm cDNA
by gi cn mang ci 'vng' si n. Sau , ci vng ny c ct b
bng cch x l vi nuclease S1 to ra cDNA si kp.
Bc 2: Xen on cDNA vo plasmid
xen on cDNA vo plasmid ngi ta c th dng enzyme end
transferase gn thm ''ui'' homopolymer (v d, CCCC....) vo cc
u 3' ca cDNA. V plasmid sau khi c m vng, cng phi lp thm
u 3' nhng trnh t tng ng l GGGG... cng vi enzyme trn. Tuy
nhin, cch ph bin hn c l gn thm vo c hai 'u bng' ca si kp
cDNA ny bng cc oligonucleotide gm 8-10 cp base, nh xc tc ca
DNA ligase T4. Sau , dng enzyme gii hn thch hp ct ''on ni''
ny to ra cc u dnh. ng thi ct plasmid bi cng mt enzyme
ti gene TetR. Hai DNA ni trn c ni vi nhau bng DNA ligase
to ra plasmid lai.
III. Cc phng php biu hin cc gene c to dng

Mt s cc vector c s dng trong cc th nghim to dng ti
t hp (nh cp) vn c th c s dng nh l nhng vector biu
hin (expression vectors). Cc vector ny c th sn sinh ra cc sn phm
protein ca cc gene c to dng. Chng hn, cc vector pUC v pBS
c xen vo DNA di s kim sot ca lac promoter, vn nm pha
268
trc so vi v tr to dng phc (multiple cloning site). Nu nh mt

on DNA c cho xen c mt trong cng khung c m th n lm gin
on gene lacZ', s sinh ra mt protein dung hp (fusion protein). N s
c mt phn trong trnh t ca protein beta-galacyosidase ti u amin v
trnh t protein khc na vn c m ha trong DNA c xen vo,
u carboxyl ca n. Tuy nhin, nu ta quan tm ti s biu hin cao ca
vector c to dng, th cc vector chuyn biu hin thng hot ng
tt hn. C hai yu t in hnh cn thit cho s biu hin gene c hot
tnh: mt promoter mnh v mt v tr bm ca ribosome m bao gm lun
c trnh t Shine-Dalgarno nm gn codon khi u AUG.
Trn thc t, ngi ta s dng cc vector biu hin c cc promoter
mnh (expression vector with strong promoters), chng hn nh promoter
ca operon tryptophan. N to thnh c s cho nhiu vector biu hin k
c ptrpL1.
Ngoi ra, ngi ta cn s dng cc vector biu hin dng cm ng
(inducible expression vectors). Trng hp ny thng tin li ch, n
gi cho mt gene c to dng trng thi ng cho ti khi ta sn sng
cho n biu hin. Mt l do l ch, cc protein ca eukaryote c sn
sinh mt s lng ln vi khun c th gy c. Ngay c cc protein vn
khng c thc s, chng cng c th c to ra nhiu n mc gy ri
lon s sinh trng ca vi khun... Promoter ca operon lactose (lac
promoter) l vector biu hin kiu cm ng n mt mc no , c l
l vn gi bt hot cho ti khi c kch hot bi cht cm ng allolactose
hoc bng cht tng hp tng t ca n l IPTG. Tuy nhin, s biu hin
vn km bi cht c ch lac l khng y hon ton, v s biu hin
no ca gene c to dng vn c th pht hin c ngay c khi
khng c mt cht cm ng. Mt cch xoay quanh vn ny l cho biu
hin gene mong mun trong mt plasmid hay phagemid m n mang c
gene lacI ca ring n, nh l plasmid pBS chng hn.
By gi chng ta th tm hiu mt phng php sn xut insulin ngi
bng con ng tng hp DNA v cho biu hin gen E. coli. Trc tin
cn lu rng, thc hin c iu ny ngi ta phi da trn thnh
tu mi nht t vic nghin cu cu trc chi tit v qu trnh tng hp cc
ch tit insulin t tuyn tu vo mu. Ni vn tt th sn phm s cp ca
qu trnh dch m t phn t mRNA hon chnh l preproinsulin gm
on peptide "tn hiu dn u" v cht tin thn ca insulin l proinsulin;
on pre- b tch b trong qu trnh tng hp. Proinsulin c ch tit l
phn t gm ba on A, B v C lin nhau trong mt cu trc "hnh quai"
c ba cu disulfur; khi on peptid C (33 amino acid) b ct b bi enzyme
269
c th trong cc ti ca t bo tuyn ty s to ra cc sn phm insulin c

hot tnh. Phn t insulin gm hai chui polypeptid A (21aa) v B (30aa)
ring bit c duy tr cng nhau bi hai cu disulfur.
T y ta c th hnh dung qu trnh tng hp gene insulin nhn to
(cDNA) v cho sn xut hormone ny E. coli nh sau. Trc tin, dng
mRNA ca proinsulin lm khun tng hp y mt DNA si kp
bng con ng phin m ngc nh trnh by trc. Sau lp
thm b ba khi u ATG nhn to (m ho amino acid u chui
polipeptide) vo u 5' bng phng php ho hc. Tip n, cho n kt
hp vi mt phn ca operon lactose (gm mt on ca gene galactosidase v ton b promoter) ca E. coli n c th hot ng
c trong t bo th nhn. Sau gene "lai" ny c xen vo plasmid
pBR322 ( y khng i su vo cc chi tit k thut, chng hn nh s
dng cc on ni, linker, v cc enzyme gii hn).
Khi a plasmid lai ny vo vi khun E. coli, n s sn sinh ra cc
protein lai gm mt on peptide ca -galactosidase ni lin vi phn t
proinsulin qua gc methionine (MET). Sau khi phn lp protein ny v x
l in vitro bng cyanogen bromide th gc MET b ct b (ko theo phn
enzyme ca vi khun l -galactosidase tch ra) v thu c proinsulin
nguyn vn. Cui cng, nh x l vi enzyme thch hp, on peptid C
gia proinsulin c tch ra v c th thu c insulin dng tinh khit.
Cng cn lu rng, hin nay ngi ta to ra c cc dng vi
khun v cc chng nm men mi c hiu c kh nng sn xut insulin
trn quy m cng nghip vi ch s insulin cao, v c bit l, cc chng
ny c th trc tip bi xut sn phm c hiu vo mi trng nui cy.
Trong trng hp , cc t bo chuyn sn xut insulin vn c duy tr
v ti s dng vi hiu qu kinh t cao.
IV. ng dng ca cng ngh DNA ti t hp

1. Cng ngh DNA ti t hp vi vic nghin cu b gene
Vic tch dng ti t hp cho php nhn c mt s lng ln bt k
gene hoc vng iu ho no tin hnh phn tch trnh t nucleotide,
xc nh cc vng chc nng v ch ra cc c ch hot ng ca chng.
Nh a li nhng hiu bit mi v t chc v hot ng ca cc b
gene prokaryote (nh cc khi im ti bn, cc vng iu ho phin m,
cc gene nhy v.v.) v cc b gene eukaryote (nh cc centromere,
telomere, cc gene phn on, cc gene gi, DNA lp li v.v.) nh
c tho lun cc chng trc.
270
DNA ngi
DNA cn to dng
v DNA plasmid
c ct bi cng
enzyme gii hn
vector YAC
ct tng phn
u dnh
cc on NST ln
u dnh
Cc plasmid cha cc
on xen khc nhau
u dnh
Ti t hp
+ DNA ligase
Nhim sc th nm men nhn to xen DNA ngi
vi khun c bin np vi
hn hp hoc cc plasmid
nui cy vi khun ch
lln ti 1.000.000 bp
Bin np vo t
bo nm men
Dng
mi dng l mt 'volume'
trong th vin gene
(a)
(b)
Hnh 10.7 Xy dng th vin gene hay th vin b gene (gene or genomic
library) bng cc th nghim to dng plasmid ti t hp vi khun (a) v
s dng nhim sc th nm men nhn to, YAC (b).
Bng cc th nghim to dng plasmid ti t hp kinh in vi khun

E. coli, v bng cch ci tin s dng nhim sc th nm men nhn to
ny (yeast artificial chromosome = YAC; hnh 10.7), ngi ta thnh lp
cc th vin gene (gene library) hay th vin b gene (genomic library)
trn c s tin hnh lp bn vt l (physical map) v xc nh trnh
t DNA b gene ca nhiu sinh vt khc nhau, k c b gene ngi
(NHGRI 2005). Nu nh vo nm 1977, F.Sanger xc nh y cc
trnh t phage X174 (5386 nucleotide vi 9 gene) v phage G4 (5577 cp
nucleotide vi 10 gene), th n nay ngi ta xc nh v lp bn cho
cc DNA c kch thc ln hn nhiu; v d: b gene phage lambda gm
48.502 cp base vi khong 61 gene (1983), nhim sc th s 3 ca nm
men Saccharomyces cerevisiae gm 370.000 cp base (1992) v.v...
ng k l, D n B gene Ngi (Human Genome Project = HGP;
hnh 10.8) chnh thc i vo hot ng t 1990 do James Watson ch
tr cng vi s cng tc ca nhiu nh khoa hc trn th gii. Vic phn
tch trnh t b gene ngi c hon thnh vo 4/2003, cho thy b
271
gene (genome) ca chng ta c trnh t y gm 3.164.700.000 cp

base, cha ng khong 25.000 gene m ha protein chu trch nhim xy
dng nn mt b protein (proteome) gm khong 50.000 protein khc
nhau trong cc t bo. HGP thc s l mt trong nhng k cng thm
him v i nht trong lch s; ln u tin HGP cho php chng ta c
c ton b thng tin di truyn ca t nhin lm nn con ngi
(NHGRI 2005).
Hnh 10.8 Biu tng ca HGP cho thy tc ng ca d n ny ln nhiu

lnh vc quan trng ca kinh t - x hi, cc vn v mi sinh, sc kho v
i sng con ngi trn phm vi ton cu.
2. Cng ngh DNA ti t hp vi y-dc hc

2.1. Sn xut cc ch phm y-sinh hc bng cng ngh DNA ti t hp
Nu nh vo nm 1972, Gio s Roger Guillemin (France) phi
dng ti 500.000 no cu mi tinh chit c vi miligram somatostatin,
mt hormone sinh trng ca vng di i th (vi cng trnh ny ng
c trao gii Nobel nm 1980), th vo 10/1977 Hebert Boyer (USA)
ch to thnh cng hormone ny t E. coli bng phng php DNA ti t
hp. n 8/1978 chnh Boyer li l ngi u tin cho sn xut thnh
cng insulin ngi t E. coli (hnh 10.9). Cc thnh tu u tin ny
m ra mt k nguyn mi pht trin rc r nht trong lch s cng ngh
sinh hc, cng ngh DNA ti t hp.
Sau l hng lot cc ch phm khc nh cc hormone tng trng
ca ngi (human growth hormone = HGH), b (BGH), ln (PGH), cc
vaccine v cc interferon phng chng cc cn bnh nan ngi y nh
ung th, vim gan v.v. v mt s bnh quan trng gia sc nh hin
tng 'l mm-long mng' do virus gy ra... tt c u c sn xut t E.
coli. c bit l, s ra i ca cc hng, cc cng ty ln u t mnh
m cho s pht trin ca k ngh ny. Nh vy gp phn gii quyt
mt cch c hiu qu nhiu vn thc tin t ra trong y hc, trong chn
nui-th y, v nng nghip ni chung ...
272
nc ta cng c mt s cng trnh nghin cu v cc vn ny,

chng hn nh nghin cu s sai khc di truyn gene hormon sinh
trng ca mt s ging g Vit Nam. Qua cho thy intron I ca gene
hormon sinh trng cc ging g Ri, g Ma, g c, g H di hn kch
thc d on ca gene hormone sinh trng g c Tanaka cng b
nm 1992 (Trn Xun Hon 2004).
Chuyn gene insulin
enzyme
gii hn
cDNA ngi on ni
To dng gene insulin

vi khun
insulin insulin
Plasmid
ti t hp
chuyn gene
insulin insulin
(a)
(b)
Hnh 10.9 (a) H. Boyer (tri) v S. Cohen; v (b) s th nghim to dng
v biu hin gene insulin ngi vi khun E. coli.
Bn cnh vic sn xut cc hormone, vaccine... ni trn, ngi ta cn

sn xut c cc khng th n dng (monocloning antibodies) dng :
(i) xc nh vi khun gy bnh (nh thng hn chng hn); (ii) xc nh
mc hormone t nh gi chc nng tuyn ni tit hoc s thay i
trong qu trnh tng hp hormone do khi u gy ra; (iii) pht hin mt s
protein c ngha trong chn on khi u hoc mt s tnh trng trc
khi sinh; (iv) pht hin cc thuc b cm c trong mu, hoc kim tra nng
thuc trong mu v t chc nhm m bo liu thuc s dng sao cho
khng vt qu ngng gy c v.v. Nh c tnh c hiu v chnh xc
cao v s dng d dng, vic sn xut cc khng th n dng to nn
mt nhnh pht trin mau l nht ca cng ngh sinh hc, v cng vi vic
sn xut cc vaccine chng tr thnh nhng phng tin quan trng
nht trong chnh sch y t cng ng ca cc nc ang pht trin v xt
v lu di, vic ng dng cc khng th n dng c trin vng cha
c nhiu bnh trong c cc khi u c tnh.
2.2. ng dng k thut di truyn trong chn on v iu tr gene
Trong chn on bnh mc phn t, thnh tu ni bt nht l vo
nm 1981, ln u tin bnh thiu mu hng cu hnh lim c chn
273
on trc sinh mc gene nh phn tch DNA bng enzyme gii hn.
T y m ra hai hng chnh trong chn on gene l: chn on cc
bt thng bm sinh v chn on cc bt thng DNA soma. Mt s
thnh tu khc t c theo hng u gm c: bnh hemophilia A, ri
lon dng c Duchenne, hi chng X-fragile, bnh retinoblastoma - mt
dng ung th vng mc...Theo hng sau, ngi ta p dng i vi mt
s dng ung th mu nh cc lympho Burkitt, lympho nang, bnh bch
cu...ng k l gn y, ngi ta xc nh c nhiu gene gy bnh
quan trng ngi, nh: gene gy bnh ha x nang (cystic fibrosis) nm
1990, gene gy bnh Huntington nm 1993...
Liu php gene (gene therapy) cng l mt phng thc sn xut v
iu tr mi bng cc phn t tr liu. y l hng c nhiu trin vng
nht nhng kh thc hin nht v n c lin quan n c vn phng
php lun ln kha cnh o l. S kin ni bt nht l vo nm 1990-91,
W.F.Anderson, R.M.Blaese v Ken Cuver thc hin thnh cng ca liu
php gene u tin trn mt b gi bn tui mc bnh suy gim min dch
phi hp (SCID) vi s thiu ht adenosine deaminase (ADA), mt
enzyme cn thit cho sn xut cc khng th trong cc t bo h mim
dch, gi l hi chng "bubble-boy" (bnh do gene gn u mt vai ngn
nhim sc th s 20 gy ra). Mt khc, liu php gene cng m ra
nhng trin vng to ln trong cha tr cc cn bnh ph bin nht, tc
ng ti hng triu triu ngi trn hnh tinh nh: ung th, SIDA/AIDS,
vim gan do virus, cc bnh tim mch, cc bnh thoi ha thn kinh (bnh
Parkinson, bnh Huntington, bnh Alzheimer...) hay c nhng bnh mn
tnh nh a thp khp.
2.3. K thut di truyn vi hnh php hc v mt s vn x hi khc
K thut di truyn cn c ng dng rt hiu qu trong cc ngnh
hnh php hc, chng hn bng cch s dng k thut 'du vn DNA'
(DNA fingerprinting) thay cho 'du vn tay' trc y cho php cc ngnh
cnh st hnh s xc nh chnh xc cc ti phm hoc nhn dng xc nn
nhn trong chin tranh hoc do tai nn gy ra (hnh 10.10).
Hnh 10.10 Du vn DNA (DNA fingerprinting) c th gip cc nh nghin cu
xc nh kh nghi trong trng hp ti
phm. Kiu vch ngang biu th bn cht
di truyn ca mt ngi. mu ny cho
thy cc bng ca mu ngi mang m s
S2 kh nghi trng khp vi bng chng,
mu mu E(vs).
274
nc ta, trong thi gian gn y, k thut ny v ang c p

dng mt cch hiu qu trong ngnh hnh s. Bn cnh c cng
trnh phn tch DNA nhn din t bo trn 103 ngi Vit Kinh bng k
thut PCR - SSO (Kit Innolipa). Qua phn tch so snh khong cch gene
hc gia ngi Vit Kinh v 11 sc tc chu v i dng khc, kt
lun rng ngi Vit Kinh gn vi ngi Thi ri n ngi Manchu (V
Triu An, 1999).
3. K thut di truyn vi cc sinh vt bin i gene (genetically modified
organisms = GMOs)
i vi ngnh chn nui, cng ngh sinh hc ni chung v cng
ngh sinh hc ni ring t nhiu thnh tu ng k, chng hn cc k
thut chuyn ghp gene p dng cho hp t v phi cc gia sc nhm
tng cng kh nng chng bnh v ci thin ging ni chung; cng nh
cc k thut mi trong xc nh gii tnh ca phi...
Hnh 10.11 cho thy kh
nng ng dng k thut cy
ghp gene trn trng chut
c th tinh. Sau em phi
ghp gene cy vo trong t
cung ca con chut lm m
khc. Kt qu l to ra c
chut con c b lng dng
khm nh mong mun. in
hnh cho cc th nghim truyn
gene ng vt l vo nm
1982,R.D.Palmiter, R.L.Brinster
v cc ng s i hc Seatle
(Philadelphia, USA) bng cch
truyn gene xc nh hormone
sinh trng ca chut cng vo
trng th tnh ca chut bnh
thng, ri cy tr li cc t bo
Tinh chit
gene
Tim
cc trng chut
Phi c cy trong t cung ca chut m thay th
i con
Hnh 10.11 M hnh tng qut v th

nghim truyn gene ng vt (xem
gii thch trong bi).
c bin i gene vo vi trng ca cc chut ci c th mang thai

cho n cng. V kt qu l, cc tc gi ny thu c dng chut nht
c kch thc ln gp 2-3 ln chut bnh thng, gi l chut khng l.
i vi trng trt, vic s dng cc phng php chuyn ghp gene
t c nhiu thnh tu to ln. Chng hn, hng Biogen (USA) nm
275
1984 chuyn thnh cng plasmid Ti vo t bo thc vt; hng Calgene

v Phytogene (USA, 1984) ghp thnh cng gene khng glyphosate
bo v cy bng; nm 1985 hng Molecular Genetics (USA) to c
ging ng mi cho nhiu tryptophan. Nm 1993, bng k thut sng bn
gene vo t bo thc vt ngi ta a c gene sn xut protein dit
su vo cy ng, v kt qu l to ra c ging ng chng chu cao
i vi su c thn. iu th v l vic tch cc gene c nh m, gene
Nif (Nif = nitrogene fixation) t cc vi khun nt sn cy h u v a
vo b gene ca cc cy trng khc to ra cc ging cy trng mi c
kh nng c nh nit v cho nng sut cao.
Trong chn ging vi sinh vt, ngi ta thc hin thnh cng vic
chuyn gene cellulase vo vi khun (J.P.Aubert, France 1/1983), ci bin
E. coli sn xut L-aspartat (hng Tanabe, Japan 1985), ghp gene vo
x khun S. violacconiger ci tin vic sn sinh enzyme glucoisomerase
(hng Roquette v Cayla, France 1985), ngoi ra cn to c cc ging
vi sinh vt bin i gene c kh nng n cn du dng trong x l cc ph
thi c c t nhm bo v mi sinh. Bn cnh vic to ra ging nm men
mi c th git cht cc vi khun xut hin trong bia (hng Suntory,
1985), cn to c chng nm men sn xut insulin v interferon (A.
Kimura, Japan 1986) v.v.
Nhn thc r ngha v tm quan trng ca cng ngh DNA ti t hp
v cng ngh sinh hc ni chung i vi s pht trin kinh t-x hi t
nc ta trong th k XXI, Chnh ph ra Ngh quyt 18/CP ngy
11/4/1994 v "Phng hng pht trin ca cng ngh sinh hc Vit
Nam n nm 2010". y c xem l mt bc ngot quan trng cho s
pht trin ca cng ngh sinh hc nc nh trong thi gian qua v sp ti.
Cu hi v Bi tp
1. Th no l enzyme gii hn? Chng c nhng tnh cht no m
c coi l cng c thit yu i vi cng ngh DNA ti t hp? Bng hai
v d v enzyme gii hn, hy chng t rng t nht c hai phng php
thnh lp cc phn t DNA ti t hp in vitro.
2. T cc enzyme gii hn BamHI, EcoRI v HindIII Bng 10.1 v
BglII c on ch c bit l AGATCT, hy cho bit cp enzyme no
s to ra cc u dnh hay u b sung (sticky/complementary ends) tng
thch? Trnh t ca u dnh tng thch ny l g?
3. Gi s bn ct hai DNA khc nhau, mt vi BamHI v mt vi
BglII, sau ni chng li vi nhau thng qua cc u dnh tng thch.
276
Mt khi khu ni ri, bn c th tch hai DNA ny ln na bng mt

trong hai enzyme gii hn hay khng? Ti sao, hoc ti sao khng?
4. Gi s bn bin np mt DNA ti t hp cho mt vi khun v do
nhm ln, bn t cc t bo c bin np trn mi trng khng c
cht khng sinh no c. Kt qu m bn quan st c l g? Ti sao?
5. Gi s rng bn chit xut c mt enzyme ct gii hn t loi vi
khun c tn khoa hc l Xenobacterium giganticus. Theo danh php
hc, bn s vit tn enzyme nh th no?
6. Cho bit trnh t ca mt on DNA c cha mt v tr nhn bit i
xng xui ngc (palindromic recognition site) cho mt enzyme gii hn
l GACGATATCAACT. Hy tm trnh t ca v tr nhn bit .
7. Th no l phn t DNA ti t hp, vector tch dng? Hy nu cc
bc ca quy trnh to dng gene ti t hp v cho s minh ho.
8. Gi s tinh ch c plasmid pBR322 v phn t DNA ngi c
cha mt gene cn nghin cu. Hy phn tch k thut to dng gene ni
trn E. coli.
9. Enzyme phin m ngc l g? N c tinh ch t loi sinh vt
no v c ng dng vo khu no trong cng ngh DNA ti t hp?
Gii thch v cho s minh ho.
10. C th s dng cc cht khng sinh xc nh xem liu plasmid
pBR322 nhn c mt on xen trong v tr EcoRI ca n hay
khng? Ti sao, hoc ti sao khng?
Ti liu Tham kho

Ting Vit
Trn Xun Hon. 2004. Nghin cu s sai khc di truyn gene hormone
sinh trng ca mt s ging g Vit Nam. Lun n Tin s Di truyn hc,
Th vin Quc gia, H Ni.
L nh Lng. 2001. Nguyn l K thut Di truyn. NXB Khoa hc v
K thut, H Ni.
Phan C Nhn. 1999. Cng ngh DNA ti t hp. Trong: Di truyn hc
tp II (Phan C Nhn, ch bin). Trang: 257-303. NXB Gio Dc, H Ni.
Hong Trng Phn. 1999. "Gii thiu cng ngh sinh hc"; v "C s
277
khoa hc ca cng ngh sinh hc". Trong: Chuyn Cng ngh Sinh hc
(Ti liu BDTX gio vin THPT chu k 1997-2000; bin son chung vi
Nguyn B Lc v Bin Vn Minh). Trang: 56-96. Trng HSP Hu.
Ting Anh
Vu Trieu An 1999. Mitochondrial DNA polymorphism in the Vietnamese
population. Eur. J. of Immunogenetics, 26: 471-422.
Collins FS, Green ED, Guttmacher AE DNA Guyer MS. 2003. A Vision
for the Future of Genomics Research. Nature, Vol.422, No.6934, p.835-847.
Hartwell, Hood, Goldberg, Reynolds, Silver, Veres. 2004. Genetics From Genes to Genomes. 2nd Edition. McGraw Hill, Inc., New York.
Lewis R. 2003. Human Genetics: Concepts DNA Applications. 5th ed,
Palladino MA. 2002. Understanding the Human Genome Project.
Benjamin/Cummings Publishing Company, Inc, Menlo Park, CA.
Molecular Biology of the Gene. 4th ed, Benjamin/Cummings Publishing
Watson JD, Gilman M, Witkowski J, Zoller M. 1992. Recombinant DNA.
2nd ed, Scientific American Books, New York.
Mt s trang web
Agricultural Biotechnology
http://www.aphis.usda_gov/biotechnology/
http://www.agbioworld.org
http://www.ncbi.nlm.nih.gov/Omim/mimstats.html
National Human Genome Research Institute (NHGRI):
http://www.ncbi.nlm.nih.gov/genome/guide/human
The Institute for Genomic Research: http://www.tigr.org
Celera Genomics Corp.: http://www.celera.com
278
Chng 11
Di truyn hc Ngi
I. Cc phng php nghin cu di truyn hc ngi
1. Phng php phn tch ph h (Genealogy analysis)
Phng php phn tch ph h c s dng nghin cu s di
truyn cc tnh trng ngi thuc cng dng h, xc nh c tnh trng
hoc bnh no l tri hay ln..., do mt hay nhiu gene qui nh, c tnh
cht di truyn hay khng, di truyn c lp hay lin kt vi gii tnh..., kh
nng mc bnh ca cc th h tip theo. Trong mt s trng hp cn xc
nh c ngi d hp t mang gene bnh. Phng php ny kt hp vi
cc xt nghim khc cho php c th rt ra nhng li khuyn v di truyn
chnh xc v hu ch cho cc gia nh v vic sinh con hoc kt hn.
Phng php ny c p dng khi bit c cc t tin trc tip v
con chu ca ngi bnh qua nhiu th h.
Mt s k hiu dng lp ph h
Nam bnh thng
Nam bnh
N bnh thng
N bnh
Gii tnh cha c xc nh
Cp sinh i khc trng
Cp v chng
Cp sinh i cng trng
Cht
y
Th d hp mang gene bnh

trn nhim sc th thng
Th d hp mang gene bnh lin kt vi nhim sc th X

Th h I
Hn nhn
II
1
III
Cc con
lit k t
tri sang
phi theo
trnh t
279
2. Phng php nghin cu tr sinh i

C hai loi sinh i l sinh i cng trng (monozygotic twin-MZ)
v sinh i khc trng (dizygotic twin-DZ). Ngi ta da vo hng lot
c im v s lng v cht lng phn bit tr sinh i cng hay khc
trng: tr sinh i cng trng bt buc cng gii, tr sinh i khc trng c
th cng hay khc gii; tr sinh cng trng c mt mng m chung, tr
sinh khc trng c mng m khc nhau; tr sinh cng trng khi ghp m
th lun lun thnh cng; c s ging nhau tr sinh i cng trng v s
khc nhau tr sinh i khc trng v nhiu tnh trng. Thng thng,
chn nhng tnh trng di truyn r rt, t b bin i di nh hng ca
cc nhn t mi trng, thuc nhng tnh trng ny c nhm mu, sc t
mt, da v tc, np vn tay, chn. Trong phn ng cy ghp m l
phng php c th kt lun mt cch chnh xc nht.
So snh cc cp sinh i v mt tnh trng hoc mt bnh no cho
php nh gi nh hng ca yu t di truyn v yu t mi trng ln s
hnh thnh tnh trng, pht hin cc bin d xy ra do yu t mi trng...
Mt bnh hoc mt tnh trng di truyn no c th biu hin c
hai thnh vin ca cp sinh i (c tng hp) hoc cng c khi ch biu
hin mt trong hai thnh vin ca cp sinh i (khng tng hp).
cc cp sinh i cng trng nu tng hp cng ln th vai tr ca
yu t di truyn cng ln. Nu tng hp cng nh th vai tr ca yu t di
truyn cng km.
3. Phng php di truyn t bo hc ngi
y l phng php c dng ph bin hin nay pht hin v
quan st nhim sc th, qua xc nh cc d dng nhim sc th, cc hin
tng lch bi, hin tng cu trc li nhim sc th dn n nhiu bnh di
truyn him ngho ngi.
Dng m gm nhiu t bo ang phn chia mnh nh m tu xng ,
m bo thai, m tinh hon, khi u c tnh...lm tiu bn phn tch, nh
gi nhim sc th.
K thut lai t bo soma v k thut hin bng nhim sc th ra i
cho php nghin cu c ch ung th, hot ng ca gene trong qu trnh
pht trin c th v gp phn tch cc vo vic lp bn di truyn ngi.
4. Phng php nghin cu qun th
Phng php ny da vo phng trnh Hardy - Weinberg, nh gi
tn s cc kiu hnh tnh mt cc gene trong qun th lin quan n
cc bnh di truyn. N cn cho php nh gi cc hu qu ca giao phi
cn huyt v theo di s di truyn ca cc qun th ngi v mt ngun
280
gc.
5. Cc k thut sinh hc phn t
Cc thnh tu to ln trong nhng nm gn y v lnh vc Di truyn
hc ngi, c bit l thnh tu gii m b gene ngi t c l nh s
dng cc k thut sinh hc phn t nh tch chit, phn tch nh tnh v
nh lng nucleic acid; cc phng php lai phn t: Southern blot,
Northern blot, lai ti ch (in situ hybridization),... ; cc phng php xc
nh trnh t nucleic acid; to dng (cloning); xy dng th vin b gene,
th vin cDNA; phng php PCR (polymerase chain reaction); Sinh tin
(Bioinfomatics),...
Ngoi cc phng php trn ngi ta cn s dng cc phng php
nghin cu m phng hc, phng php in v phn tch np vn da,
phng php iu tra dch t hc v phng php di truyn lm sng...
trong nghin cu Di truyn hc ngi.
II. Cc phng php lp bn di truyn ngi

1. Phn tch lin kt (Linkage analysis)
S trao i cho gia cc locus trn cng nhim sc th c th to ra
ti t hp. Vic nh gi tn s ti t hp c th thc hin da vo quan st
s di truyn cc allele trong cc gia nh. S xc nh cc phase lin kt
(c ngha l nhim sc th m trn mi mt allele c nh v) l mt
phn quan trng ca phng php ny.
Mc d c s tng quan gia centiMorgan v khong cch vt l
tht s gia cc locus, mi quan h ny b phc tp do cc sai khc v gii
tnh trong ti t hp, cc tn s ti t hp cao hn gn cc telomere v s
tn ti ca cc im nng ti t hp (recombination hot spots).
S sai khc v thng k ca 2 locus c th c tnh ton bng cch
tnh t s ca hai hp l (likelihood): hp l ca lin kt tn s ti t hp
cho chia cho hp l ca khng lin kt. Logarithm ca t s sai khc ny
c k hiu l LOD (logarithm of odds). LOD>0,3: c lin kt; LOD<0,2: khng lin kt.
Khong cch gia cc locus c tnh bng n v centiMorgan
(cM). 1 cM tng ng vi tn s ti t hp xp x 1%.
Phn tch lin kt cho php chng ta xc nh c khong cch
tng i gia cc locus nhng khng xc nh c cc v tr c trng
vi marker hoc cc gene bnh.
2. Cc phng php lp bn vt l (physical mapping)
2.1. Phng php lp bn mt on (delection mapping)
281
Karyotype ca cc bnh nhn mc bnh di truyn thnh thong c

pht hin thy hin tng mt on mt vng c trng trn nhim sc th.
iu ny cho thy rng locus gy bnh c th nm trong vng b mt.
Chiu di on b mt c th bin i mt s bnh nhn mc cng mt
bnh. Cc on mt ca nhiu bnh nhn c so snh xc nh vng b
mt tt c cc bnh nhn, do thu hp li v tr ca gene bnh. Phng
php lp bn mt on c s dng xc nh v tr cc gene chu
trch nhim i vi ung th vng mc (retinoplastoma), hi chng Prader
Willi v Angelman v khi u Wilms. Khi u Wilms l mt khi u thn
giai on u do t bin nhim sc th s 11 gy ra. Ch rng cc mt
on ny ch xy ra mt nhim sc th trong cp tng ng, to ra bnh
nhn d hp t i vi on b mt. Nu on b mt ln c th quan
st d dng di knh hin vi v xy ra trn c hai nhim sc th ca cp
tng ng th thng gy cht.
2. 2. Phng php lai ti ch (In situ hybridization)
on DNA thu c t marker a hnh hoc gene bnh m chng ta
mun bit v tr c to dng vi mu d (probe) bng k thut DNA ti
t hp. Mu d c nh du vi cht phng x nh tritium chng hn.
Sau mu d c t vo mt mng lai cha nhim sc th k gia m
DNA ca n bin tnh. Mu d phng x s bt cp b sung vi DNA
bin tnh ca on nhim sc th c trng. Bi v mu d pht ra bc x
nn v tr ca n c th c xc nh mt cch chnh xc bng cch t
mt phim nhy cm tia X ln trn mng lai (phng x t ghi
(autoradiography)).
Phng php lai ti ch s dng cc mu d phng x thng din ra
chm v mc phn tch kh thp (2-5 Mb). K thut FISH (fluorescence in
situ hybridization) s dng mu d hunh quang thay cho mu d phng x
l nhanh hn v cho php phn tch vng ca mu d tt hn, thng l
trong khong 1 Mb i vi nhim sc th k gia. Bng cch s dng
nhim sc th k trung gian, cc nhim sc th k ny kt xon t hn cc
nhim sc th k gia, phn tch FISH c th c tng ln t 25-250 kb.
2.3. Lai t bo soma
Cc t bo soma ca cc loi khc nhau khi sinh trng trong cng
mi trng nui cy vi s c mt ca mt s tc nhn nh polyethylene
glycol hoc virus Sendai, thnh thong s dung hp vi nhau to thnh cc
t bo lai. Khi lai cc t bo chut v t bo ngi vi nhau s thu c cc
t bo lai cha 86 nhim sc th : 46 nhim sc th ngi v 40 nhim sc
th chut. Sau cc t bo lai c php sao chp. Cc t bo ny bt u
mt i mt s nhim sc th ngi khi chng tri qua qu trnh nguyn
282
phn. Cui cng cc t bo cn li b nhim sc th y ca chut v

ch mt hoc mt s nhim sc th ngi. Cc t bo ny c lp
karyotype xc nh nhim sc th no ca ngi cn li (nhim sc th
ca ngi v chut c th c phn bit vi nhau da vo kch thc v
cc phng php hin bng). Sau cc t bo ny c nghin cu
xc nh t bo no mang gene thch hp ang ni n. V d nu gene
lun lun c tm thy trong cc t bo cha nhim sc th s 1 ca ngi
nhng cha bao gi c pht hin trong cc t bo khng mang nhim sc
th s 1, chng ta c th kt lun rng gene ny phi c nh v trn
nhim sc th s 1.
S c mt ca gene trong t bo lai c th c pht hin bng mt
s phng php. Nu gene m ho mt enzyme c sn xut ra bi t bo
th mt xt nghim enzyme c th c s dng. in di protein c s
dng nhn ra mt sn phm protein ngi v phn bit n vi sn
phm protein tng ng ca chut. Tuy nhin cc phng php ny yu
cu mt sn phm protein bit phi c pht hin. Thng thng hn,
hin nay cc nh nghin cu kim tra s lai ca cc dng t bo dung hp
vi mt mu d nh du phng x mang DNA quan tm bng cch s
dng phng php Southern blotting hoc k thut PCR.
2.4. Lp bn lai phng x (Radiation hybrid mapping)
Phng php ny bt u vi mt th lai t bo soma cha mt
nhim sc th n ca ngi. Sau cc t bo ny c chiu vi tia X
hoc tia lm t gy si kp nhim sc th. Bc x ny git cht t bo
v vy chng phi c dung hp vi t bo ng vt gm nhm tn ti.
Mt s t bo lai c to ra gi l cc th lai phng x (radiation hybrid)
mang cc on nh nhim sc th ngi lai vi nhim sc th gm
nhm. S c mt ca nhim sc th ngi c th c pht hin bng s
sng lc i vi cc trnh t Alu. Cc trnh t Alu ny tm thy mi mt
on c kch thc vi kb trong nhim sc th ngi nhng khng tm thy
trong nhim sc th ca gm nhm. Bi v bc x b gy nhim sc th
ngi nhng khong cch ngu nhin, cc locus c nh v gn vi
mt locus khc hn s c tm thy thng hn trn cng on nhim sc
th (c xu hng cng i vi nhau). K thut PCR c th c s dng
xc nh th lai phng x mang cc t hp c trng ca cc locus ngi.
Sau s dng phng php thng k nh gi mi mt cp locus
thng c tm thy trn cng on nhim sc th nh th no. Kt qu
ny cung cp s nh gi khong cch tng i gia cc locus.
Ngoi cc phng php trn ngi ta cn dng cc phng php to
dng nh v (positional cloning), phn tch s bo tn ca cc loi lai
283
(analysis of cross-species conservation), phn tch trnh t DNA bng my

tnh, sng lc cc t bin trong trnh t (screen for mutations in the
sequence), kim tra s biu hin ca gene....
III. Nhim sc th Y v cht nhim sc gii tnh ca ngi
1. Nhim sc th Y ca ngi
Tri ngc vi nhim sc th X, nhim
sc th Y hon ton nh v cha rt t gene.
Phn ln chiu di ca nhim sc th Y khng
xy ra ti t hp l cht d nhim sc. Cc on
lp DNA ca n c xem xt t m.
Cc vng tng ng ca cp nhim sc
th XY c nh v mi u ca nhim sc
th Y. Cc vng ny kt cp v ti t hp vi
nhim sc th X trong k u ca gim phn I.
Chng c gi l cc vng nhim sc th
thng gi (pseudoautosomal region-PAR) bi
v
bt k gene no nh v trong cc vng ny
Hnh 11.1
(cho
n nay ch mi pht hin c 9 gene)
Nhim sc th
u c di truyn hon ton ging nh gene
Y ca ngi
trn nhim sc th thng. Nam c hai bn sao
ca cc gene ny: mt trong PAR ca Y v
mt trong vng tng ng ca X.
Khong 95% chiu di ca Y nm gia
cc PAR to ra vng khng tip hp (nonrecombining region-NRY). Gn 80 gene
c tm thy y. Chng c xp thnh 2
nhm chnh. Cc gene thuc nhm th nht (m
ho cc protein s dng cho tt c cc t bo (c
hai gii)) c bu hin nhiu m. Cc gene
gi nh ny (housekeeping gene) c th tng
ng trn X m trnh khi s bt hot X n.
Cc gene thuc nhm th hai m ho cc
Hnh 11.2
protein hot ng chc nng ch trong tinh
S tip hp ca
hon v khng c th tng ng trn X. Mt
nhim sc th X
gene c vai tr quan trng trong nhm ny l
v Y
SRY (sex-determing region Y). SRY nh v
trn cnh ngn nm bn ngoi PAR v gy ra
cc kh nng bin i phi thnh nam gii.
284
2. Cht nhim sc gii tnh ca ngi

t lu ngi ta bit rng
n c hai nhim sc th X trong khi
nam ch c mt nhim sc th X.
Nh vy mi gene lin kt vi nhim
sc th X c hai bn sao i vi n
v mt bn sao i vi nam. Nu tt
c cc gene trn nhim sc th X u
hot ng th n hm lng cc
cc sn phm (nh enzym chng
hn) do cc gene ny m ha phi
nhiu gp i nam. Trong thc t
hm
lng cc sn phm trn u
Hnh 11.3
S bt hot ca nhim sc th X bng nhau c hai gii. C th gii
thch iu ny nh th no ?
Vo u thp nin 1960, Mary Lyon gi thuyt rng mt nhim
sc th X trong mi t bo soma ca n b bt hot. Hin tng ny dn
n kt qu c gi l s b p v liu lng gene (Gene dosage
compensation) lm cho sn phm ca gene lin kt vi nhim sc th X ca
nam v n ngang nhau. Gi thuyt Lyon cho rng s bt hot nhim sc th
X xy ra sm trong giai on pht trin phi ging ci. mt s t bo,
nhim sc th X b bt hot c ngun gc t b, trong khi nhng t bo
khc nhim sc th X b bt hot c ngun gc t m. Qu trnh bt hot
ny l ngu nhin. Khi mt nhim sc th X b bt hot trong mt t bo,
n s duy tr s bt hot ny tt c cc th h t bo con chu. Nh vy
s bt hot nhim sc th X l ngu nhin nhng li c c nh.
S bt hot nhim sc th X s dn n kt qu l tt c c th ci
bnh thng c hai qun th t bo phn bit: mt qun th c nhim sc
th X hot ng nhn c t b v mt qun th c nhim sc th X hot
ng nhn c t m. Vi hai qun th t bo ny, ging ci l dng
khm i vi nhim sc th X, ging c ch c mt bn sao ca nhim sc
th X l dng bn hp t (hemizygous) i vi nhim sc th X.
Gi thuyt Lyon a ra mt s bng chng, phn ln nhn c t
cc nghin cu v ng vt v ngi.
Cc nghin cu ca Di truyn hc trong thp k 1940 cho thy
rng cc t bo gian k ca mo ci thng cha mt khi cht nhim sc
dy c bt mu thuc nhum trong nhn t bo. Cc khi ny cha bao
gi tm thy ging c. Chng c gi l th Barr, do Murray Barr, mt
nh Di truyn hc m t chng. Barr gii thch rng th Barr tng
285
ng vi mt nhim sc th X kt c cao. Trng thi kt c ny phn nh

thc t l ADN ca n c ti bn chm hn ADN cc nhim sc th khc
trong pha S.
Cc nghin cu tip theo xc nh mARN c sao chp ch t
mt nhim sc th X trong t bo ca con ci bnh thng. Qu trnh bt
hot xy ra khong hai tun sau khi th tinh. Qu trnh c khi u
mt v tr n (single location) trn cnh di ca nhim sc th X (trung
tm bt hot X) v sau tri di dc theo nhim sc th. S bt hot ca
nhim sc th X l thng xuyn i vi tt c cc t bo soma con ci,
nhng n phi tr nn hot ha trong dng t bo mm ca c th ci, do
vy mi t bo trng s nhn c mt bn sao ca nhim sc th X hot
ng.
Theo gi thuyt Lyon, s lng th Barr trong cc t bo soma l
lun lun bng s nhim sc th X tr i 1. C th ci bnh thng c mt
th Barr trong t bo soma trong khi cc con c li khng c. Nam b hi
chng Klinefelter (XXY) c mt th Bar. Dng hi chng ny dn n
mt cu hi: Nu nhim sc th X tha b bt hot th ti sao ngi mang
nhim sc th X tha c kiu hnh khng bnh thng ? Cu tr li l s
bt hot ca nhim sc th X l khng hon ton. Mt vi vng ca nhim
sc th X bt hot vn hot ng tt c cc bn sao. Mt nghin cu mi
y cho thy 20% gene ca nhim sc th X bt hot c th vn hot ng.
Cc gene ny l tng ng vi cc gene trn nhim sc th Y v cc bn
sao ca chng gp phn to nn s khng bnh thng ca kiu hnh.
Trung tm bt hot X cha gene cn thit cho s bt hot c tn l
XIST (X-inactive specific transcript), gene ny c sao m thnh mARN
15-17 kb nhng khng c dch m.
Mt im c bit khc ca nhim sc th X bt hot l s methyl
ha, c kh nng l s methyl ha chu trch nhim duy tr s bt hot ca
mt nhim sc th X c bit trong t bo.
IV. S di truyn cc gene tri ln trn nhim sc th thng v

nhim sc th gii tnh
1. S di truyn cc gene tri ln trn nhim sc th thng
1.1. S di truyn cc gene tri trn nhim sc th thng
Bnh di truyn do cc gene tri trn nhim sc th thng c bt
gp vi tn s khong 1/200. Nu tnh ring l th mi bnh di truyn do
gene tri trn nhim sc th thng l kh him trong qun th. Tuy nhin,
cc bnh ph bin nht c tn s gene khong 0,001. Tnh trng hay bnh
di truyn do cc gene tri trn nhim sc th thng c mt s cc c
286
im quan trng. Th nht, c hai gii biu hin tnh trng vi t l gn nh

nhau. B v m c vai tr ngang nhau trong vic truyn tnh trng cho con
ci. Th hai, khng c s ngt qung th h: kiu hnh bnh c truyn t
ng b sang b m, ri t b m cho con ci...Nu b m khng b bnh th
s khng truyn bnh cho con ci. V vy kiu biu hin ny c gi l
kiu di truyn phn b dc (vertical transmission pattern). Th ba, mc d
s truyn tnh trng t b cho con trai khng c yu cu nh gi s
di truyn gene tri trn nhim sc th thng nhng s hin din ca n
trong mt ph h loi tr chc chn cc kiu di truyn khc (c bit l s
di truyn lin kt vi nhim sc th X). Cui cng, th d hp t mang gene
bnh truyn tnh trng ny cho gn mt na con ci ca h.
1.2. S di truyn cc gene ln trn nhim sc th thng
Ging nh bnh di truyn do cc gene tri trn nhim sc th thng,
cc bnh di truyn do gene ln trn nhim sc th thng l kh him trong
qun th. Ch khi trng thi ng hp th mi biu hin thnh kiu hnh.
Cc th d hp l ph bin nhiu hn th ng hp. S di truyn cc gene
ln trn nhim sc th thng c mt s c im quan trng. Th nht,
kiu hnh bnh biu hin mt hoc nhiu anh ch em nhng khng pht
hin thy cc th h trc . Do vy kiu di truyn ny c gi l kiu
di truyn phn b ngang (horiziontal transmission pattern). Th hai, ging
nh trng hp di truyn do gene tri trn nhim sc th thng, nam v
n u c kh nng b mc bnh vi t l ngang nhau. Th ba, trung bnh
khong 1/4 con ci ca cp b m d hp s b mc bnh. Cui cng, tnh
ng huyt (consanguinity) thng hin din trong cc ph h lin quan
n bnh do gene ln trn nhim sc th thng nhiu hn so vi cc ph
h lin quan n cc kiu di truyn khc.
2. S di truyn cc gene tri ln trn nhim sc th gii tnh
2.1. S di truyn gene ln lin kt vi nhim sc th X
Mt s cc tnh trng v bnh ni ting l do cc gene ln lin kt
vi nhim sc th X gy ra. Cc kiu di truyn do gene ln lin kt vi
nhim sc th X chc chn l khc vi gene trn NST thng. Bi v n
c di truyn hai bn sao nhim sc th X. n, tnh trng do gene ln
lin kt vi nhim sc th X rt ging vi trng hp tnh trng do gene
ln trn nhim sc th thng quy nh. Tuy nhin, ch c mt nhim sc
th X l bt hot trong t bo, nh vy mt na s t bo ca n d hp t
s biu hin allele bnh v na cn li s biu hin allele bnh thng.
Trong lc nam c di truyn mt allele bnh ln lin kt vi nhim
sc th X th s biu hin bnh v nhim sc th Y khng mang allele tng
ng.
287
Mt bnh do gene ln lin kt vi nhim sc th X vi tn s q th tt

c nam c t bin s biu hin bnh. N phi cn hai bn sao ca allele
t bin biu hin bnh do tn s biu hin s l q2 nh trng hp
bnh do gene ln trn nhim sc th thng quy nh. Kt qu ny cho thy
rng nam b tc ng mt cch thng xuyn v nhiu hn so vi n i
vi bnh do gene ln lin kt vi nhim sc th X.
Mt s c im phn bit tnh trng hoc bnh do ln lin kt vi
nhim sc th X vi tnh trng hoc bnh do gene ln trn nhim sc th
thng:
- Cc gene lin kt vi nhim sc th X khng c truyn trc tip
t b cho con trai.
- Gene lin kt vi nhim sc th X c th c truyn t b cho tt
c con gi, nhng con gi ny khng c biu hin bnh nhng c mang
gene bnh. Cc con gi mang gene bnh ny s truyn li cho mt na s
con trai ca h, cc con trai ny b bnh. Kiu di truyn ny gy ra s xut
hin cc th h ngt qung (skipped generations).
Kiu ghp i ph bin i vi cc gene ln lin kt vi nhim sc
th gii tnh X l s kt hp ca m mang gene bnh vi b bnh thng.
M s truyn gene bnh cho mt na s con trai v mt na s con gi.
Mt kiu ghp i ph bin khc l gia b b bnh vi m bnh
thng. Tt c con trai ca h bnh thng. Bi v tt c con gi phi nhn
nhim sc th X ca b do chng s tr thnh th mang gene bnh d
hp t. Nh vy khng c mt a con no biu hin bnh.
Kiu ghp i t ph bin hn l gia b b bnh vi m l th mang
gene bnh. Mt na s con gi ca h s tr thnh th mang gene bnh d
hp t, mt na s ng hp t gene bnh v s biu hin bnh. Mt na
s con trai bnh thng v mt na s con trai b bnh.
Thnh thong c trng hp n ch nhn mt bn sao n ca gene
ln gy bnh lin kt vi nhim sc th gii tnh m c th b bnh. Cc c
th n ny c gi l th d hp biu hin (manifesting heterozygotes).
Bi v cc c th n ny thng duy tr t nht mt phn nh ca nhim sc
th X hot ng bnh thng v c khuynh hng biu hin bnh tng i
nh. V d, gn 5% n d hp t i vi bnh a chy mu A (hemophilia
A) c mc yu t ng mu VIII thp c xp vo loi bnh a
chy mu nh.
t ph bin hn l n ch c mt nhim sc th X (hi chng Turner)
biu hin cc bnh do gene ln lin kt vi nhim sc th X, nh bnh
a chy mu A. N cn c th b cc bnh do gene ln lin kt nhim sc
288
th X l kt qu ca s chuyn on hoc mt on nhim sc th X. Cc

trng hp ny l him.
2. 2. S di truyn cc gene tri lin kt vi nhim sc th X
S di truyn do gene tri lin kt vi nhim sc th gii tnh X
ging nh s di truyn do gene tri trn nhim sc th thng. Mt c th
ch cn tha hng mt bn sao n ca gene tri lin kt vi nhim sc
th X l c th biu hin tnh trng hoc bnh. Bi v n c hai nhim sc
th X, m mi nhim sc th X u c th c kh nng mang gene bnh
nn n b bnh gn gp i so vi nam (tr trng hp ri lan gy cht
nam). B b bnh khng th truyn tnh trng ny cho con trai. Tt c con
gi u di truyn gene bnh ny v th u b bnh. B b bnh thng l d
hp t v vy s c 50% c hi truyn allele bnh cho con gi v con trai.
2.3. S di truyn lin kt vi nhim sc th Y
S tnh trng hoc bnh bit do gene trn nhim sc th Y qui nh
l rt t, ch gp nam gii v c truyn trc tip t b cho con trai
mang tnh cht dng h ni. Tt c cc con trai u b bnh (di truyn
thng) v con gi khng mang bnh. Cc bnh lin kt vi nhim sc th Y
nh tt nhiu lng mc vnh tai, dy sng lng bn tay, tt dnh ngn s
2 v 3...
V. Di truyn y hc
1. Cc bnh di truyn do ri lon chuyn ho v cc bnh nhim sc th
1.1. Cc bnh di truyn do ri lon chuyn ho
1.1.1. Phenylketonuria (PKU)
PKU l mt d tt bm sinh, c di truyn do gene ln Mendel.
PKU c Phelling pht hin ln u tin vo vo nm 1934.
Tr s sinh b bnh ny l do t bin gene, gan khng c kh nng
tng hp phenylalanine hydroxylase nn dn n tnh trng khng ch km
hm s chuyn ho phenylalanine thnh tyrozine m cn gy ra ng
phenylalanine trong mu, lm tng s phn gii phenyalanine thnh axit
phenylpyruvic, cng b tch t trong mu. C phenylalanine v
phenylpyruvic khi ln no nhiu s u c t bo thn kinh. Bn thn
nc tiu thi ra cng c phenylalanine.
Nu t bin gene ln xy ra mt khu khc lm km hm hot
ng ca enzyme tyrozinase, l enzyme xc tc phn ng chuyn ho
tyrozine thnh melanine dn ti bch tng.
Nhiu nc ngy nay t ra th tc chn on cho mi tr s
sinh, pht hin sm dng ng hp PKU cho n khu phn king c
289
bit ngho phenylalanine (cho sa nga) hoc khu phn n khng c

phenylalanine (rau, mt ong, b,...)
1.1.2. Alcaptonuria
Bateson,1902 v Garrod, 1907 chng minh rng bnh ny do mt
gene ln, thng xy ra cc gia nh c ngi cng dng mu ly nhau.
Biu hin ca bnh ny rt d nhn bit: nc tiu ca bnh nhn c mu
en do trong nc tiu cha mt lng ln axit homogenetizic. ngi
bnh thng, axit homogenetizic s c enzyme oxydase phn gii thnh
axit axetoaxetic. Khi thiu enzyme oxydase th axit homogenetizic khng
c phn gii v thi ra theo nc tiu, b oxy ho trong khng kh to
thnh mt hp cht c mu en. Khi cn b tt bm sinh ny cha gy hu
qu nghim trng nhng khi ng tui b vim khp nng, sn tch lu
nhiu sc t.
1.2. Cc bnh nhim sc th
Nh s pht trin ca cc phng php nghin cu di truyn hc
ngi, c bit l phng php di truyn t bo lm r c ch pht sinh
nhiu loi bnh nhim sc th, do s phn ly khng bnh thng ca nhim
sc th trong qu trnh phn bo hoc do d dng, sai hnh nhim sc th t
cc ri lon trong cu trc, hnh thi.
1.2.1. Hi chng Down
Hi chng ny c Langdom Down pht hin ln u tin vo nm
1866. Tn s bt gp khong 1/700 tr s sinh v l bnh nhim sc th bt
gp cao nht. Thng th b nhim sc th ca bnh nhn c 47 chic, tha
mt nhim sc th 21. Trong mt s trng hp hi chng ny cn l kt
qu ca chuyn on gia nhim sc th 21 vi nhim sc th ca nhm D
hoc nhm G. Biu hin bnh l l ngu n bm sinh, gim tr lc, nhiu d
tt cc c quan ni tng, khng c kh nng sinh dc, vc dng b, ln,
c rt, u b, chm dt, mt trn, khe mt xch, mi dy, li dy c xu
th th ra thng xuyn...S liu v hi chng Down tr em Vit Nam
c trnh by trong chng 3.
1.2.2. Hi chng Klinefelter
H. F.Klinefelter m t hi chng ny ln u tin vo nm 1942.
Tn s bt gp l khong 1/1000 b trai sinh ra. Kiu nhn ca bnh nhn
l 47, XXY. Nguyn nhn c th l do th thai t mt t bo trng XX vi
tinh trng Y hoc t mt trng X vi tinh trng XY. Bnh nhn l nam
khng bnh thng v tuyn sinh dc, c mt s nt ging n , c v nh
n, c bit l cc tnh trng gii tnh th cp, tr tu km pht trin, khng
c con, kh ngi cao, chn tay di (Hnh 11.4).
290
1.2.3. Hi chng Turner

Hi chng ny c H.H.Turner pht hin ln u tin vo nm
1938. Tn s bt gp khong 1/3000 tr em gi s sinh. Kiu nhn ca
bnh nhn l 45, X. Nguyn nhn l do mt t bo trng hoc mt tinh
trng khng c nhim sc th gii tnh, hoc do mt i mt nhim sc th
gii tnh trong nguyn phn nhng ln phn ct u tin sau khi hnh
thnh hp t XX hoc XY. Bnh nhn c tm vc b, thng b cc d hnh
nh khng c bung trng, thiu cc tnh trng gii tnh th cp do
khng c con v nhiu d dng b ngoi khc (Hnh 11.5).
Hnh 11.4 Hi chng Klinefelter
Hnh 11.5 Hi chng Turner
291
Cn ni thm l, Vit Nam, c cc s liu nghin cu c cng

b v cc bt thng nhim sc th trong cc th bnh Leukemia cp, mt
dng bnh tng bch cu, hoi huyt (Phm Quang Vinh, 2003).
2. C s di truyn ung th
C mt s bng chng r rng cho thy rng ung th l mt bnh do
s bin i ca gene gy ra. Cc t bo khi u c s lng nhim sc th
bin i v cc nhim sc th thng c s sp xp li. Mt vi chuyn
on l c trng vi cc dng ung th nht nh. Phn ln cc tc nhn
t bin l cc tc nhn gy ung th. T bm (predisposition) vi cc dng
ung th c tm thy l di truyn mt s gia nh. C ba loi gene
lin quan n ung th c pht hin l gene ung th (oncogene), gene
c ch khi u (tumor suppressor gene) v gene sa cha DNA (DNA repair
gene).
Phn ln gene ung th c ngun gc t protooncogene.
Protooncogene l cc gene m ho cc sn phm kim sot s sinh trng
v bit ho ca t bo. Protooncogene c hot ho to thnh gene ung
th do t bin hoc biu hin qu mc. Ln u tin chng c pht hin
trong cc retrovirus gy ung th, nhng cng c th c pht hin trong
cc khi u khng c virus bng s chuyn nhim vo trong cc t bo 3T3
ca chut. Gene ung th cc retrovirus l v-onc v khi trong cc khi u
l c-onc. Thnh thong gene ung th c khuych i trong cc t bo
khi u. Phn ln cc gene ung th hot ng nh allele tri lm tng chc
nng t bin dn n loi b kh nng iu ho ca s kim sot chu trnh
t bo. Ngc li vi gene c ch khi u, gene ung th khng biu hin cc
t bin dng mm (germline mutations) m cc t bin ny gy nn cc
hi chng ung th di truyn (inherited cancer syndromes). Trong khi
t bin soma gy ra ung th n pht (sporadic cancer).
Mt s khi u do chuyn on c hiu lm tng s phin m ca
gene ung th c m t c im. Hin tng ny c tm thy
u lympho ca Burkitt (Burkitts lymphoma).Hoc s dung hp ca hai
protooncogene c th to thnh mt gene mi l vi cc c tnh ung th
c quan st bnh bch cu dng tu mn tnh (chronic myeloid
leukemia).
Gene c ch khi u cn n c hai bn sao tr nn bt hot trc khi
cc khi u c th pht trin. Cc t bin ny l t bin ln. Thng
thng s bt hot xy ra l do t bin im mt allele v mt mt allele
khc. S bt hot ca gene c ch khi u xy ra cc t bo soma trong
qu trnh pht trin ca khi u. Gene c ch khi u c nghin cu k
nht l gene p53. Trong hn 40% cc khi u ca ngi, gene ny b t
292
bin. p53 ng vai tr iu ho chu trnh t bo v qu trnh cht theo

chng trnh ca t bo (apoptosis)
Mt s ung th him gp v mt phn nh ung th ph bin tp
hp li trong mt s gia nh. Cc gia nh ny c gi l c t bm di
truyn (hereditary predisposition) vi ung th. T bm di truyn ny c th
tr thnh mt dng c trng ca ung th v d nh ung th v hoc mt
loi ung th khc.
T bm di truyn c th tng ln thng qua cc t bin dng mm
ca gene c ch khi u. Tt c cc t bo soma ca mt c th mang mt
allele t bin v c nguy c hnh thnh khi u tng cao do s bt hot ca
mt allele n bnh thng. V d ngi gm c gene vng mc
(retinoblastoma -Rb) nm trn nhim sc th 13 v gene t bm di truyn
ung th v v ung th bung trng (BRCA1) nm trn nhim sc th 17.
Allele bnh thng b bt hot trong khi u. Cc gene ung th gia nh
thng b t bin soma trong cc trng hp khng thng xuyn (khng
di truyn) ca cng loi ung th.
Ung th di truyn cho thy kiu di truyn do gene tri trn nhim sc
th thng bi v ngi bnh truyn t bm di truyn cho mt na s con
ci ca h. Tuy nhin cc t bin gene c ch khi u l t bin ln. N
c gii thch bng thc t l nu mt c th ch c mt bn sao hot ng
chc nng ca gene c ch khi u trong mi t bo th n rt thch hp cho
vic mt t bin th hai s gy bt hot bn sao hot ng chc nng bnh
thng ny trong mi t bo. Sau cc t bo t bin kp ny c th
pht trin thnh mt khi u.
Cc gene sa cha DNA cng kt hp vi ung th di truyn. V d
bnh da sng ho sc t (xeroderma pigmentosum) do mt t bin ln trn
nhim sc th thng. Ngi bnh rt nhy cm vi nh sng mt tri bi
v h thiu endonuclease xc tc cho vic sa cha DNA. Cc allele t
bin ca mt s gene khc c th dn n t bm ung th rut kt (colon
cancer). Hai trong s cc t bin ny cng lin quan n s sa cha cc
DNA khng hp i (DNA mismatches). Cc t bo khi u sa cha DNA
tn thng t hiu qu hn cc t bo bnh thng v to ra cc t bin
vi tn s cao v mt s cc t bin s tr thnh cc gene c ch khi u
hoc protooncogene. y l kiu hnh ca gene tng cng t bin
(mutator phenotype).
VI. T vn di truyn y hc (Medical genetic counseling)

T vn di truyn y hc hay cn gi l li khuyn di truyn, l s trao
i kin, gii thch v nguyn nhn, c ch v mt bnh tt di truyn no
v cho li khuyn v kh nng mc bnh i con ca cc cp v
293
chng m bn thn h hoc mt s ngi trong dng h mc phi bnh y.

Li khuyn di truyn nhm mc ch gip cc cp v chng n xin li
khuyn di truyn t quyt nh c nn sinh con hay khng v nu sinh th
phi nh th no trnh cho ra i cc a tr tt nguyn gim gnh
nng cho gia nh v x hi, cng nh cung cp cho h cc phng php,
bin php phng, iu tr v hn ch cc hu qu cho bn thn v cho
con ci.
c c li khuyn di truyn chnh xc, nh t vn di truyn y
hc phi tm hiu tin s gia nh, theo di ph h, xc nh ng l bnh
di truyn v y l t bin tri hay ln v di truyn theo qui lut no, thm
khm cho ngi b bnh v trong mt s trng hp phi thm khm cho
c nhng ngi c lin quan trong gia nh, lm cc xt nghim chn on.
Cc i tng cn xin li khuyn di truyn l cc cp v chng c
con ci b bnh di truyn; cc nam n thanh nin trc khi xy dng gia
nh khi m mt trong hai gia nh hoc c hai gia nh c ngi mc
bnh di truyn; nhng ngi b v sinh, sy thai lin tc,...; cc cp v
chng mun sinh con theo mun; c hai v chng hoc ch v hay chng
lm vic trong iu kin c hi; bit v hoc chng mang gene bnh;
cc cp v chng ln tui, c bit l ngi v v nhng ngi kt
duyn cng dng h...
Trc y li khuyn di truyn hon ton da vo s hiu bit v qui
lut di truyn, tnh xc sut xy ra cho tng trng hp c th, phn tch
ph h xc nh bnh di truyn theo qui lut no...Ngy nay k thut
chn on trc sinh c thc hin vi nhng phng php phn tch
ng tin cy ngay khi c th cn giai on phi thai trong c th m nh
phng php chc d dch i phn tch di truyn hc t bo v ho sinh,
quan st gin tip bo thai nh siu m, quan st trc tip bo thai bng soi
phi thai, ly cc mu sinh phm t phi thai (mu, tua nhau thai...) xt
nghim, phng php nh lng AFP (alpha feto protein) trong mu m.
Chn on trc sinh cho php nh gi tnh trng ca b nhim sc th,
ca b gene, tnh trng hot ng ca cc enzyme trong bo thai gip t
vn di truyn y hc c c s khoa hc chc chn cho li khuyn chnh
xc.
Cu hi v Bi tp
1. Mt cp v chng c mt a con b bnh u x nang. y l mt
bnh him gp, c quy nh bi mt t bin lndi truyn theo nh lut
Mendel. Cp v chng ny d nh sinh thm con. Hy tnh xc sut
a cob tip theo: (a) Mang gene bnh; (b) Khng b bnh.
294
2. ngi, tnh trng tc qun tri so vi tnh trng tc thng, do

gene nm trn nhim sc th thng quy nh; cn bnh m mu do gene
ln nm trn nhim sc th gii tnh X gy nn. B v m c tc qun, mt
bnh thng sinh ra mt con trai tc qun, m mu. Hy xc nh kiu gene
ca b m.
3. B m u c nhm mu A, sinh con trai c nhm mu A, con gi
c nhm mu O. Hy tm kiu gene chc c ca nhng ngi trong gia
nh trn.
4. Kt qu thng k trn mt s lng ln cc a tr sinh ra t nhiu
cp v chng, trong cc ngi chng u b bnh xn men rng cn cc
ngi v c men rng bnh thng cho thy: 50% b bnh xn men rng
u l gi : 50% c men rng bnh thng ton l trai. Hy xc nh tnh
cht di truyn ca bnh xn men rng v vit s lai t P n F1. Cho bit
tnh trng men rng do mt gene quy nh.
5. Chng bnh thng, ly v b bnh mu kh ng. Con ca h c
b bnh mu kh ng khng?
6. "Bnh m mu v bnh mu kh ng l bnh ca nam gii".
Quan nim nh vy c ng khng? Hy gii thch ti sao.
7. Trnh by cc phng php nghin cu di truyn ngi.
8. Trnh by cc phng php lp bn di truyn ngi.
9. Nu c im di truyn ca cc gene tri-ln trn nhim sc th
thng v nhim sc th gii tnh.
10. Trnh by mt s bnh di truyn do ri lon chuyn ho v cc
bnh nhim sc th.
Ti liu Tham kho

Ting Vit
Trn Quc Dung. 2003. Bi ging Di truyn hc ngi. Trng i hc S
phm Hu, Hu.
Phan C Nhn, Nguyn Minh Cng, ng Hu Lanh. 1999. Di truyn hc
ngi. Trong: Di truyn hc (Phan C Nhn , ch bin). Tp II. Trang:
161-248. NXB Gio Dc.
Ting Anh
Doris Bachtrog, Brian Chalesworth. 2001. Towards a complete sequence of
the human Y chromosome. Genome Biol 2 (5): reviews 1016.1- reviews
1016.5. Published online 2001 April 26.
295
Jorde, Carey, Bamshad, White. 2000. Medical Genetics. Printed in the

United States of America.
Winter P. C., Hickey G.I., Fletcher H. L. 1998. Genetics. Printed by
Biddles Ltd, Guilford, UK.
http://users.rcn.com/jkiball.ma.ultranet/BiologyPages/S/SexChromosomes.
html
http://cas.bellarmine.edu/tietjen/HumanBiology/bill_developmental_abnor
malities.htm
296
Chng 12
Di truyn hc Qun th
Ln u tin vo nm 1908, G.Hardy v W.Weinberg chng minh
rng tnh di truyn t n khng lm thay i tn s allele trong qun th,
sau ny c gi l nguyn l Hardy-Weinberg (Hardy-Weinberg
principle). N t nn mng cho di truyn hc qun th (population
genetics) - mt nhnh ca di truyn hc - nghin cu thnh phn di truyn
ca cc qun th sinh vt v cc qu trnh nh hng ln cc tn s gene
ca chng. Tuy nhin, n u thp nin 1930 lnh vc nghin cu ny
mi thc s pht trin nh cc cng trnh v i ca R.A.Fisher, J.B.S.
Haldane v S.Wright m thc cht l cc m hnh ton hc. T di
truyn hc qun th tr thnh nn tng ca cc thuyt tin ho hin i.
Trong chng ny, chng ta s tho lun mt s khi nim c bn ca
di truyn hc qun th, nguyn l Hardy-Weinberg v mi quan h gia
cc tn s allele v kiu gene trong cc trng hp khc nhau, ni phi v
s gia tng tn s ca cc th ng hp, v tm hiu s lc vai tr ca cc
nhn t tc ng ln thnh phn di truyn qun th.
I. Cc khi nim c bn ca Di truyn hc qun th

1. Qun th (population)
Trong tin ho, c th khng c xem l n v thch hp bi v: kiu
gene ca mt c th c gi nguyn trong qung i ca n; hn na, c
th c tnh tm b (d n c th sng ti c nghn nm nh cy tng...).
Ngc li, mt qun th th c tnh lin tc qua thi gian v mt khc,
thnh phn di truyn ca n c th thay i tin ho qua cc th h. S
hnh thnh cc qun th a phng ti nhng vng lnh th khc nhau
chnh l phng thc thch ng ca loi trc t nhin. Qun th v vy
c xem l n v tin ha c s.
Theo A.V.Yablokov (1986), qun th l mt nhm cc c th cng
loi c kh nng giao phi t do vi nhau, chim c mt khu phn b xc
nh v tri qua mt khong thi gian tin ho lu di hnh thnh nn
mt h thng di truyn c lp v mt sinh thi ring.
Ni ngn gn, qun th l mt nhm sinh vt c kh nng giao phi
qua li v cng chia x mt vn gene chung (Ridley 1993). N cn c
gi l qun th Mendel, m tp hp ln nht l loi (species).
2. Cc h thng giao phi (mating systems)
Trn nguyn tc, cu trc di truyn ca qun th th h sau c xc
nh bi xc sut kt hp ca cc giao t th h trc trong qu trnh th
297
tinh. Do , n ph thuc vo kiu giao phi ca cc b m. Trong di

truyn hc qun th, ngi ta phn bit ba kiu giao phi: Giao phi ngu
nhin hay ngu phi (random mating hay panmixia), giao phi chn la
(assortative mating), v ni phi (inbreeding).
- Ngu phi l kiu giao phi trong xy ra s bt cp ngu nhin
gia cc c th c v ci trong qun th.
Lu rng nh ngha qun th trn y c p dng cho cc qun
th thuc h thng ngu phi; chng chim v tr rt quan trng trong h
thng cc loi v c cp ch yu trong sut ch ny.
- Giao phi chn la l kiu giao phi trong cc c th c v ci
khng bt cp ngu nhin m c s la chn theo kiu hnh. C hai trng
hp: (1) Nu nh cc c th c xu hng giao phi vi cc c th khc c
kiu hnh tng t, th gi l giao phi chn la dng tnh (positive
assortative mating); v (2) Nu nh s la chn t c quan tm nhng
tn s ca cc cp giao phi vn khc xa vi tn s ca cc cp ngu phi,
th gi l giao phi khng la chn (disassortative mating) hay chn la
m tnh (negative assortative mating). Chng hn, ngi, s giao phi
c la chn xy ra i vi cc tnh trng nh chiu cao, mu mt, mu
tc...V vy n ch nh hng n cc tn s kiu gene ca locus no c
lin quan n vic xc nh kiu hnh c s dng trong giao phi. Cn
kiu giao phi khng la chn ph bin trong cc h thng t bt dc
(self-sterility) thc vt.
- Ni phi l s giao phi khng ngu nhin xy ra gia cc c th c
quan h h hng gn hoc in hnh l s t th tinh (xem mc IV).
3. Vn gene (gene pool)
Vn gene l tp hp ton b cc allele tt c cc gene ca mi c th
trong qun th ti mt thi im xc nh.
Vn gene ny c s dng chung cho cc c th trong qun th. Mi
qun th c trng bng mt vn gene nht nh v n c m t bng
tn s cc allele tng locus.
4. Tn s kiu gene v tn s allele
m t thnh phn di truyn ca mt qun th ta cn phi xc nh
kiu gene ca cc c th v s c th ca mi kiu gene. Gi s trong mt
qun th sinh vt lng bi gm N c th, xt mt locus A thuc nhim
sc th thng (autosome) vi hai allele A1 v A2 c mt trong cc c th.
Lc s c ba kiu gene: A1A1, A1A2 v A2A2 vi s lng tng ng l
N11, N12 v N22; (N = N11 + N12 + N22). Nu k hiu P, H v Q l tn s
tng ng vi cc kiu gene trn, ta c:
298
P = N11 / N; H = N12 / N v Q = N22 / N ; (P + H + Q = 1)

T y ta c th tnh c cc tn s gene hay allele (gene or allelic
frequencies) A1 v A2, vi k hiu tng ng l p v q ( p +q =1), nh sau:
2 N 11 + N 12
1
p=
=P+ H
2N
2
1
2 N 22 + N 12
q=
=Q+ H
( hay q =1-p )
2
2N
Tm tt:
(1) Vn gene ca mt qun th c N c th bao gm 2N h gene n
bi. Mi h gene gm tt c cc thng tin di truyn nhn c t mt cha
m. i vi mi locus autosome, trong vn gene qun th s c 2N allele.
(2) Tn s kiu hnh (phenotypic frequency) bng s lng c th ca
kiu hnh c th chia cho tng s c th ca qun th.
(3) Tn s kiu gene (geneotypic frequency) bng s lng c th ca
kiu gene c th chia cho tng s c th ca qun th.
(4) Tn s allele (allelic frequency) bng hai ln s lng c th ng
hp cng vi s c th d hp v allele chia cho hai ln tng s c th
ca qun th; hay tn s ca mt allele bng tn s kiu gene ng hp
cng vi mt na tn s kiu gene d hp v allele .
Lu : (i) Tng cc tn s kiu hnh, kiu gene hay allele thuc mt
locus no lun lun bng n v; (ii) Tn s allele hay tn s gene nh
mt s nh khoa hc thng gi (Crow 1986; Falconer v Mackay 1996)
l khi nim cn bn nht ca di truyn hc qun th; n l du hiu c
trng ca mt qun th cho php phn bit vi cc qun th khc trong
cng mt loi; (iii) cho tn s cc allele quan st c l c trng ca
mt qun th, th mu thu c phi l ngu nhin v c kch thc
ln; (iv) tin cho mt s mc ch m t cc bin d di truyn mt
locus, ngi ta s dng ch yu tn s cc allele ch khng phi tn s
cc kiu gene, bi v mt locus thng c s allele t hn s kiu gene;
(v) Thut ng "thnh phn" hay "cu trc di truyn ca qun th" dng
ch tn s tng i ca cc allele v cc kiu gene trong qun th ti mt
thi im xc nh.
V d: S liu phn b ca h nhm mu M-N mt s qun th ngi
bng 12.1 cho thy: (1) Mi qun th mt vng a l nht nh u
c cc tn s allele c trng ; (2) Trong khi qun th ngi M gc u
c cc tn s allele M v N hu nh tng ng, mc d tn s allele M
cao hn khong 8%, th qun th th dn c c tn s allele N rt cao
299
(nhiu gp 4,6 ln tn s allele M); cn b tc da Navaho ni ring

v vng Trung-Nam M ni chung c tn s allele M rt cao.
Bng 12.1 Tn s cc nhm mu h M-N mt s qun th ngi
Qun th
S lng
Tn s kiu gene
MN
M M
M N
N N
L L
L L
L L
Tn s allele
LM
LN
Btc Navaho
305
52
0,845
0,144
0,011
0,917 0,083
Th dn c
22
216
492
0,030
0,296
0,674
0,178 0,822
1787 3039 1303
0,292
0,496
0,213
0,539 0,461
M gc u
II. Nguyn l Hardy-Weinberg v trng thi cn bng ca qun

th
1. Nguyn l Hardy-Weinbeirg
Nm 1908, nh ton hc ngi Anh Godfrey H.Hardy v bc s ngi
c Wilhelm Weinberg c lp chng minh rng c tn ti mt mi
quan h n gin gia cc tn s allele v cc tn s kiu gene m ngy
nay ta gi l nh lut hay nguyn l Hardy-Weinberg (vit tt: H -W ).
1.1. Ni dung nguyn l H-W
Trong mt qun th ngu phi kch thc ln, nu nh khng c p
lc ca cc qu trnh t bin, di nhp c, bin ng di truyn v chn lc,
th tn s cc allele c duy tr n nh t th h ny sang th h khc v
tn s cc kiu gene (ca mt gene gm hai allele khc nhau) l mt hm
nh thc ca cc tn s allele, c biu din bng cng thc sau:
( p + q )2 = p2 + 2pq + q2 = 1
1.2. Chng minh
mt qun th Mendel, xt mt locus autosome gm hai allele A1 v
A2 c tn s nh nhau c hai gii c v ci. K hiu p v q cho cc tn
s allele ni trn (p + q =1). Cng gi thit rng cc c th c v ci bt
cp ngu nhin, ngha l cc giao t c v ci gp g nhau mt cch ngu
nhin trong s hnh thnh cc hp t. Khi tn s ca mt kiu gene no
chnh l bng tch ca cc tn s hai allele tng ng. Xc sut mt
c th c kiu gene A1A1 l bng xc sut (p) ca allele A1 nhn t m
nhn vi xc sut (p) ca allele A1 nhn t b, hay p.p = p2. Tng t,
xc sut m mt c th c kiu gene A2A2 l q2. Kiu gene A1A2 c th
xut hin theo hai cch: A1 t m v A2 t b vi tn s l pq, hoc A2 t
m v A1 t b cng vi tn s pq; v vy tn s ca A1A2 l pq + pq =
2pq (Bng 12.2). iu chng minh trn c tm tt nh sau:
300
* Qun th ban u c 3 kiu gene : A1A1 A1A2 A2A2

Tng
Tn s cc kiu gene :
P
H
Q
Tn s cc allele :
p = P + H ; q = Q + H
1
* Qun th th h th nht sau ngu phi c :
Tn s cc kiu gene = (p + q)2 = p2 + 2pq + q2
1
2
Tn s cc allele: f(A1) = p + (2pq) = p(p+q) = p
f(A2) = q2 + (2pq) = q(p+q) = q
Nhn xt:
T chng minh trn cho thy cc tn s allele th h con ging ht
th h ban u, ngha l f(A1) = p v f(A2) = q. Do , cc tn s kiu gene
th h tip theo vn l p2, 2pq v q2 (ging nh th h th nht sau
ngu phi). iu chng t rng cc tn s kiu gene t c cn bng
ch sau mt th h ngu phi. Trng thi n nh v thnh phn di truyn
c phn nh bng cng thc H-W nh vy c gi l cn bng H-W
(Hardy-Weinberg equilibrium).
Bng 12.2 Cc tn s H-W sinh ra t s kt hp ngu nhin cc giao t
Tns
gt c
Tn s giao t ci
p(A1)
q(A2)
p(A1)
p2(A1A1)
pq(A1A2)
q(A2)
pq(A1A2)
q2(A2A2)
1.3. Cc mnh v h qu
(1) Nu nh khng c p lc ca cc qu trnh tin ho (t bin, di
nhp c, bin ng di truyn v chn lc), th cc tn s allele c gi
nguyn khng i t th h ny sang th h khc. y l mnh chnh
ca nguyn l hay nh lut H-W.
(2) Nu s giao phi l ngu nhin, th cc tn s kiu gene c quan h
vi cc tn s allele bng cng thc n gin: ( p+q )2 = p2 + 2pq + q2 =1.
(3) H qu 1: Bt lun cc tn s kiu gene ban u (P, H, Q) nh th
no, min sao cc tn s allele hai gii l nh nhau, ch sau mt th h
ngu phi cc tn s kiu gene t ti trng thi cn bng (p2, 2pq v q2).
(4) H qu 2: Khi qun th trng thi cn bng th tch ca cc tn s
ng hp t bng bnh phng ca mt na tn s d hp t, ngha l:
(2 pq ) 2
p2.q2 = [
]
2
301
Tht vy, khi qun th trng thi cn bng l tng, ta c: H = 2pq

Bin i ng thc trn ta c: pq = H
Bnh phng c hai v, ta c: p2.q2 = (H)2, trong H = 2pq. Nh
vy ng thc ny cho thy mi tng quan gia cc thnh phn ng hp
v d hp khi qun th trng thi cn bng l tng.
(5) H qu 3: (i) Tn s ca cc th d hp khng vt qu 50%, v
gi tr cc i ny ch xy ra khi p = q = 0,5 H = 2pq = 0,5; lc ny cc
th d hp chim mt na s c th trong qun th; (ii) i vi allele him
(tc c tn s thp), n chim u th trong cc th d hp ngha l, tn s
th d hp cao hn nhiu so vi tn s th ng hp v allele . iu ny
gy hu qu quan trng i vi hiu qu chn lc (xem thm mc 1.5.2
di y).
1.4. Tn s giao phi v s kim chng nguyn l H-W
Nguyn l H-W c th c chng minh theo mt cch khc da trn
tn s ca cc kiu giao phi. Mc d n cng knh hn phng php
xt nhng li cho thy r hn bng cch no cc tn s H-W pht xut t
quy lut phn ly ca Mendel.
Xt cu trc giao phi ca qun th ngu phi nh trn ta thy c c
thy l chn kiu giao phi vi tn s giao phi nh Bng 12.3. V tn s
mi kiu gene hai gii c xem l nh nhau, nn mt s kiu giao
phi thun nghch l tng ng v vy ch cn li su kiu giao phi
khc nhau vi tn s tng ng c nu hai ct u tin ca bng 12.4.
By gi ta xt cc kiu gene i con sinh ra t mi kiu giao phi v sau
tm tn s ca mi kiu gene trong ton b i con, vi gi thit rng
tt c cc kiu giao phi u hu th ngang nhau v tt c cc kiu gene
u c sc sng nh nhau. Kt qu ny c trnh by pha bn phi
Bng 12.4. Sau khi rt gn ta c cc tn s kiu gene i con tng ng
l p2 , 2pq v q2 ( dng cui cng ca bng). Cc tr s ny chnh l cc
tn s cn bng H-W (equilibrium frequencies) t c sau mt th h
ngu phi, bt lun cc tn s kiu gene i b m nh th no.
Bng 12.3 Tn s ca cc kiu giao phi ngu nhin
Gii c
Gii ci
A1A1 (P)
A1A2 (H)
A2A2 (Q)
A1A1
(P)
A1A2
(H)
A2A2
(Q)
P2
PH
PQ
PH
H2
QH
PQ
QH
Q2
302
Bng 12.4 Nguyn l Hardy-Weinberg i vi hai allele

B m
i con
Kiu giao phi Tn s
A1A1
A1A2
A2A2
A1A1 A1A1
P2
P2
A1A1 A1A2
2PH
PH
PH
A1A1 A2A2
A1A2 A1A2
2PQ
H2
H2
2PQ
H2
H2
A1A2 A2A2
A2A2 A2A2
2HQ
Q2
HQ
HQ
Q2
Tng
(P+H)2 =p2 : 2(P+H)(Q+H) =2pq : (Q+H)2 = q2
2. Nhng ng dng ca nguyn l Hardy-Weinberg

2.1. Xc nh tn s ca allele ln
Trong trng hp tri hon ton, ta khng th phn bit cc th d hp
vi th ng hp tri. V vy, trn nguyn tc, ta khng th tnh c cc
tn s allele. Tuy nhin, c th gi nh cc tn s kiu gene dng cn
bng, qua tnh c tn s allele ln v d on tn s ca cc kiu
gene trong qun th. Chng hn, bch tng (albinism) ngi l tnh
trng ln tng i him gp. Nu nh k hiu A cho allele xc nh sc t
bnh thng v a cho allele bch tng, kiu gene ca ngi b bch tng l
aa, trong khi nhng ngi bnh thng th hoc l AA hoc l Aa. Gi s
trong mt qun th ngi tn s ca nhng ngi b bch tng l 1/10.000.
Theo nguyn l H-W, tn s ca th ng hp ln l q2 = 0,0001 nn q
= f (aa) = 0,0001 = 0,01. Do tn s ca allele A l: p = 1 0,01 =
0,99 (v p + q = 1). T y xc nh c tn s ca hai kiu gene cn li:
f(AA) = p2 = (0,99)2 = 0,9801 (hay ~98%)
f(Aa) = 2pq = 2(0,99)(0,01) = 0,0198 (hay ~ 2%)
Lu trong trng hp tn s allele ln l rt thp, ngha l kch thc
mu ln, ta cn phi ly s thp phn y m bo chnh xc cho
cc kt qu tnh ton sau cng.
2.2. Xc nh tn s ca cc "th mang" (carrier)
Mt iu l th ca nguyn l H-W l ch, cc allele him ni chung
l cc allele ln gy bnh trong qun th thng n tng trong cc th d
hp (gi l th mang) v ta c th tnh c tn s ca chng nu nh
bit c tn s allele. Nu cho rng c s cn bng H-W th tn s ca
cc th mang allele bnh ln trong qun th c c tnh l H = 2q(1-q).
303
V tn s ca cc th d hp trong s nhng c th bnh thng, k hiu

H, l t s f(Aa)/ f(AA+Aa), trong a l allele ln vi tn s q. Khi :
2q
2 pq
2q (1 q)
=
=
H = 2
2
p + 2 pq
(1 q) + 2q(1 q ) 1 + q
V d: Vi trng hp bch tng ni trn, tn s ca aa l 0,0001 th
tn s ca nhng ngi d hp (Aa) l 0,02 , ngha l trong 50 ngi c
mt ngi mang allele bch tng. y l mt t l rt cao! Mt khc, tn
s allele a nhng ngi d hp l 0,02: 2 = 0,01 trong khi nhng ngi
bch tng l 0,0001, nh vy allele a nhng ngi d hp c nhiu hn
nhng ngi bch tng khong 100 ln (0,01 : 0,0001 = 100 ).
Tng qut, nu tn s ca mt allele ln trong qun th l q, th s c
pq allele ln trong cc th d hp v q2 allele ln trong cc th ng hp.
T s y l pq/q2 = p/q, v nu nh q rt b th t s s xp x 1/q. Nh
vy, khi tn s ca mt allele ln cng thp bao nhiu, th t l ca allele
trong cc th d hp cng cao by nhiu.
Tng t, c th ly nhiu v d v cc allele ln gy bnh ngi.
in hnh l bnh ri lon chuyn ho c tn l phenylxetn-niu
(phenylketonuria = PKU) do mt allele ln n, c th pht hin sm vi
ngy sau sinh. Mt kt qu iu tra Birmingham trong hn ba nm cho
thy c 5 trng hp b bnh trong s 55.715 b (Raine v cs 1972). Tn
s cc th ng hp ln xp x 1/11.000 hay 90 x 10-6. Tn s allele ln l
q = 90 x10 6 = 0,0095. Tn s cc th d hp trong c qun th (H = 2pq)
v trong s cc th bnh thng (H= 2q/1+q) u xp x bng 0,019. Nh
vy khong 2% s ngi bnh thng l c mang mm bnh PKU. Cc kt
qu ny tht ng ngc nhin: bng cch no cc th d hp v allele ln
li ph bin n nh vy, trong khi tn s bnh thc t l qu thp!
n y ta c th khng nh rng: Nu nh ai c tng mun
loi b mt allele ln him gy bnh no ra khi qun th hng ci
thin chng tc chng hn, qu l khng tng! Tht vy, nu gi t l s
th h cn thit bin i tn s allele ban u l q0 xung cn qt th h
th t, ta c t =1/qt -1/q0. Gi s q0 = 0,01, mun gim xung cn 0,001
phi cn ti 900 th h; tng t, gim tn s xung cn 0,0001 phi
cn n 9.900 th h. Th tng tng ngi mt th h trung bnh l
30 nm, thi gian y ln n dng no (9.900 x 30 = 297.000 nm)!
2.3. Kho st trng thi cn bng ca qun th
T nguyn l H-W v cc h qu rt ra c trn cho php ta vn
dng xc nh xem cu trc di truyn ca mt qun th c trng thi
304
cn bng H-W hay khng.

Di y ch lc trnh vi phng php tng qut i vi mt qun
th ngu phi (Hong Trng Phn 2001), vi cc gi thit v k hiu
c cp. Trc tin, cn nm vng nguyn tc ny trong suy lun:
Theo nguyn l H-W, cc tn s kiu gene i con c xc nh nh
tn s allele b m chng. Nu qun th trng thi cn bng, tn s cc
allele s nh nhau c hai th h, v vy tn s allele quan st c i
con c th dng y nh th n l tn s allele i b m tnh cc tn s
kiu gene k vng theo nguyn l H-W. Nh vy, v nguyn tc, mt
qun th c coi l trng thi cn bng nu nh n tha mn mt trong
nhng kh nng sau y; ngc li, qun th khng trng thi cn bng.
(1) Cc tn s kiu gene quan st c (P, H v Q) phi xp x bng
cc tn s k vng tng ng (p2, 2pq v q2), ngha l thnh phn di
truyn ca qun th phi tho mn cng thc H-W.
V mt s lng, qun th c coi l trng thi cn bng nu nh
c s ph hp st sao gia cc con s quan st v k vng i vi mi kiu
gene, ngha l: N11 p2N ; N12 2pqN; v N22 q2N.
(2) Tn s th d hp quan st phi xp x bng tn s k vng
(H 2pq), ngha l: p.q H hay P.Q (H)2
(3) Tn s ca mi kiu gene quan st c gia hai th h lin tip l
tng ng nhau. Nu ta gi tn s ca cc kiu gene A1A1, A1A2 v
A2A2 tng ng th h th nht l P1, H1v Q1 v th h th hai l P2,
H2 v Q2, lc : P1 P2 ; H1 H2; v Q1 Q2.
(4) i vi trng hp kho st cn bng H-W hoc giao phi ngu
nhin da trn tn s giao phi hoc s lng cp giao phi ca cc kiu
giao phi khc nhau, ta c th so snh nh sau:
Kiu giao phi
A1A1
A1A1
A1A1
A1A2
A1A2
A2A2
Tng
x
x
x
x
x
x
A1A1
A1A2
A2A2
A1A2
A2A2
A2A2
Tn s
S lng
Quan st K vng
2
Quan st
2
K vng
P
2PH
2PQ
H2
2QH
Q2
p .p
2(p2)(2pq)
2(p2)(q2)
(2pq)(2pq)
2(2pq)(q2)
q2.q2
P .N/2
2P.H.N/2
2P.Q.N/2
H2.N/2
2Q.H.N/2
Q2.N/2
p2.p2.N/2
2(p2)(2pq)N/2
2(p2)(q2)N/2
(2pq)(2pq)N/2
2(2pq)(q2)N/2
q2.q2.N/2
N/2
N/2
305
(5) Phng php Khi-bnh phng (Chi-square method)

Khi so snh gia cc s liu quan st v k vng thng c th c s
sai lch khng ng k hoc ng k. V ranh gii phn nh gia chng l
khng r rng khin ta kh m khng nh qun th trng thi cn bng
hoc khng. Trong trng hp , ta phi s dng phng php 2 (xem
chng 1).
V d: kho st trng thi cn bng H-W, ta hy xt qun th ngi
M da trng gc u cho bng 12.1. T s ngi mang cc nhm mu
M, MN vN tng ng l 1.787; 3.039; v 1.303 (vi N = 6.129), ta tnh
c tn s ca cc allele M v N l p v q nh sau:
p = 1.787 + 1/2(3.039) = 0,539
v q = 1 - p = 0,461.
T y tnh c tn s k vng ca cc kiu gene:
MM p2 = (0,539)2 = 0,292
MN 2pq = 2(0,539)(0,461) = 0,497
NN q2 = (0,461)2 = 0,211
V s c th k vng ca chng:
MM p2 N = 0,292 6.129 = 1.787,2
MN 2pq N = 0,497 6.129 = 3.044,9
NN q2 N = 0,211 6.129 = 1.296,9
So snh cc s liu quan st v k vng v tng kiu gene ta thy c
s ph hp st sao, chng t qun th trng thi cn bng H-W.
Tht vy, nu kim tra bng trc nghim 2, ta c:
2 =
(1787 1787,2) 2 (3039 3044,9) 2 (1303 1296,9) 2

+
+
= 0,04
1787,2
3044,9
1296,9
Tra bng phn phi 2 ng vi P = 0,05 v 1 bc t do ta tm c tr

s 2 bng 3,84. V tr s thc t l rt nh so vi tr s l thuyt, chng t
gia cc s liu quan st v k vng hu nh trng khp nhau hon ton;
ngha l, qun th trng thi cn bng H-W.
III. M rng nguyn l Hardy-Weinberg

Sau y ta ln lt xt xem kh nng p dng nguyn l H-W vo ba
trng hp: mt gene c nhiu hn hai allele (a allele), mt gene c hai
allele vi tn s khc nhau hai gii tnh, v gene lin kt vi gii tnh.
1. a allele (multiple alleles)
Vi qun th ngu phi nh ni trc, y ta ch thay gi thit
306
mt locus A c ba allele: A1, A2 v A3 vi tn s tng ng l p1, p2 v p3

(p1 + p2 + p3 = 1). Khi trong qun th c tt c su kiu gene vi s
lng c th tng ng nh sau :
Kiu gene : A1A1 A2A2 A3A3 A1A2 A1A3 A2A3 Tng
S lng : N11 N22 N33
N12
N13
N23
N
Theo nguyn tc, ta tnh c cc tn s allele:
p1 = N11 + (N12 + N13)
p2 = N22 + (N12 + N23)
p3 = N33 + (N13 + N33)
Bng cch lp bng t hp ngu nhin ca cc giao t v tn s ca
chng, hoc bng cch khai trin bnh phng ca mt tam thc ta tnh
c cc tn s cn bng H-W ch sau mt th h ngu phi nh sau:
(p1 + p2 + p3)2 = p12 + p22 + p32 + 2p1p2 + 2p1p3 + 2p2p3 = 1
Tng qut, mt locus c n allele s c tt c n(n + 1)/ 2 kiu gene, trong
gm n kiu ng hp v n(n 1)/2 kiu d hp. Tn ca mt allele bt
n
k (pi) c tnh theo cng thc:
pi = pii +
Pij
i j =1
trong pii - tn s kiu gene ng hp v pij- tn s kiu gene d hp.

V d: Thng thng h nhm mu ABO c ly v d cho ba allele.
V cc allele IA vIB l ng tri v allele IO l ln, nn trong qun th
ngi bt k no cng s c bn nhm mu A, B, AB v O ng vi su
kiu gene. tnh cc tn s allele trong trng hp ny ta phi gi nh
qun th trng thi cn bng. t tn s ca cc allele IA, IB v IO ln
lt l p, q v r (p + q + r =1). Khi ta tnh c tn s H-W ca cc
nhm mu chnh l cc tn s quan st c (bng 12.5).
Phng php tnh cc tn s allele nh sau: Trc tin, tn s allele IO
(r) bng cc cn bc hai ca tn s nhm mu O (r2). Tn s ca hai allele
cn li, p v q, c tnh bng cch kt hp tn s H-W ca mt nhm
mu A hoc B vi nhm mu O theo mt trong hai phng php sau:
Phng php 1
2
Ta c f(A+0) = p +2pr + r = (p + r)
p+r =
p=
f ( A + 0)
f ( A + O) r
Tng t, ta c :
Phng php 2
2
V p +q +r = 1 q +r = 1 p
Bnh phng 2 v ta c:
(1 p)2 = (q + r)2 = f (B + O)
1p=
f ( B + O)
307
q=
f ( B + O) r
p=1
f ( B + O)
Tng t, ta c: q = 1
f ( A + O)
Mt cch tng i, ta c th tnh p hoc q ri suy ra ci cn li da

vo tng p + q + r =1. Tuy nhin, nu tnh cn thn c ba tn s theo mt
trong hai phng php trn ta s bit c tr s thc ca chng. Khi
tng cc tn s allele tnh dc s khng ng bng n v mt cch chnh
xc. iu ny c l gii l do t l cc kiu gene trong mu khng phi
l cc t l H-W chnh xc v hn na, nhm mu AB khng c s
dng trong tnh ton. V vy, khi kiu hnh khng c s dng n (
y l nhm mu AB) m c tn s cao hn th s mt mt thng tin s
nghim trng hn, v phi cn n mt phng php chnh xc hn.
Bng 12.5 Tng quan gia cc nhm mu, kiu gene v tn s ca chng
Nhm mu
Kiu gene
A
B
O
AB
IAIA + IAIO
IBIB + IBIO
IOIO
IAIB
Tng
Tn s
K vng
Quan st
p2 + 2pr
q2 + 2qr
r2
2pq
0,41716
0,08560
0,46684
0,03040
1,0
By gi ta hy xt mt mu nghin cu trn 190.177 phi cng vng

quc Anh (UK) gm 79.334 A, 16.279 B, 88.782 O, v 5.782 AB ( Race
v Sanger, 1954; dn theo Falconer 1989). Tng quan gia cc nhm
mu, kiu gene v cc tn s ca chng c trnh by bng 12.5.
p dng hai phng php trn ta tnh c cc tn s allele nh sau:
Allele
Tn s
Phng php 1
Phng php 2
IA
IB
IO
0,2569
0,0600
0,6833
0,2567
0,0598
0,6833
Tng
1,0002
0,9998
308
2. Tn s allele sai bit gia hai gii tnh

Trn thc t, cc tn s allele nhim sc th thng hai gii tnh c
th khc nhau. Chng hn, trong chn nui gia sc - gia cm tu theo mc
tiu kinh t l ly sa, tht hoc trngm tng quan s lng c th
c-ci s khc nhau. Khi vic p dng nguyn l H-W s nh th no?
xt qun th ny, ta s dng k hiu v gi thit sau :
Allele
Tn s
Gii c
Gii ci
A1
A2
p
q
p
q
Tng
Bng cch lp bng t hp ca cc giao t, ta xc nh c cu trc

di truyn ca qun th sau mt th h ngu phi:
(pA1 : qA2)(pA1 : qA2) = ppA1A1 : (pq+ pq) A1A2 : qqA2A2
R rng l n khng tha mn cng thc H-W. By gi n lt tn s
cc allele ca qun th ny l nh sau:
f(A1) = pp+ (pq+ pq)
Thay gi tr q= 1 p, ta c:
f(A1) = (p + p)
Tng t: f(A2) = (q +q)
t f(A1) = p v f(A2) = q , khi cu trc di truyn qun th th h
tip theo s tho mn cng thc H-W: p2 A1A1 : 2pqA1A2 : q2A2A2.
iu chng t rng, nu nh cc tn s allele (autosome) khi u
l khc nhau hai gii, th chng s c san bng ch sau mt th h
ngu phi v qun th t trng thi cn bng sau hai th h.
V d: Mt qun th khi u c tn s cc allele A v a hai gii nh
sau: p = 0,8; q= 0,2; p = 0,4; v q = 0,6. Nu nh ngu phi xy ra, th
th h th nht c tn s cc kiu gene l: 0,32AA : 0,56Aa : 0,12aa.
V tn s cn bng ca mi allele lc nh sau:
p = (0,8 + 0.4) = 0,32 + (0,56) = 0,6
q = (0,2 + 0,6) = 0,12 + (0,56) = 0,4
th h th hai, qun th t cn bng vi cc tn s H-W l:
0,36AA : 0,48Aa : 0,16aa
309
3. Cc gene lin kt trn X

Trong trng hp cc gene lin kt vi gii tnh, tnh hnh tr nn
phc tp hn rt nhiu. gii ng giao t, mi quan h gia tn s allele
v tn s kiu gene tng t nh mt gene autosome, nhng gii d giao
t ch c hai kiu gene v mi c th ch mang mt allele. cho tin, ta
coi gii d giao t l gii c. By gi ta xt hai allele A1 v A2 vi tn s
tng ng l p v q, v t cc tn s kiu gene nh sau:
Kiu gene:
A1A1
A1A2 A2A2 A1
A2
Tn s :
P
H
Q
R
S
Theo nguyn tc, ta xc nh c tn s ca mt allele (v d A1):
- gii ci (pc):
pc = P + H
- gii c (p):
p = R
- chung c qun th ( p ): p = pc + p
Lu : Mi con ci c hai nhim sc th X v mi con c ch c mt
X; v t l c : ci trn nguyn tc l 1:1, cho nn 2/3 cc gene lin kt
gii tnh trong qun th l thuc v gii ci v 1/3 thuc v gii c. V
vy, tn s ca cc allele A1 trong c qun th l: p = pc + p.
R rng l cc tn s allele hai phn c v ci l khc nhau, do
qun th khng trng thi cn bng. Trong khi tn s allele trong c
qun th khng thay i qua cc th h, nhng s phn phi cc allele
gia hai gii c s dao ng khi qun th tin dn n s cn bng. iu
ny c chng minh nh sau. Theo quy lut lin kt gene trn X, cc con
c nhn cc gene lin kt gii tnh ch t cc c th m, v vy p th
h con bng vi pc th h trc; cc con ci nhn cc gene lin kt gii
tnh ng u t c hai b m, v vy pc th h con bng trung bnh cng
ca p v pc th h trc. Nu dng du phy trn u ch tn s
allele th h con, ta c:
p = pc
pc = (pc + p)
T y xc nh c mc chnh lch hay l hiu s gia cc tn s
allele ca hai gii: pc p = (p + pc) pc = (pc p)
Ngha l, hiu s ca cc tn s allele gia hai gii th h con bng
mt na hiu s ca cc tn s allele gia hai gii th h b m ca n,
nhng ngc du. Nh vy, s phn b cc allele gia hai gii c s giao
ng theo quy lut sau: C sau mt th h, mc chnh lch gim i mt
na v nh th qun th tin dn n trng thi cn bng cho n khi cc
tn s gene hai gii l cn bng nhau, ngha l pc = p = p .
310
V d: Theo kt qu mt mu nghin cu trn mo Lun n (Searle,

1949; trong Falconer 1989) cho thy trong s 338 mo ci c 277 con lng
en (BB), 54 con th khm (BO) v 7 con lng da cam (OO), v trong s
353 mo c c 311 en (B) v 42 da cam (O). Tnh trng ny tun theo
quy lut di truyn kin kt vi gii tnh nh cp trc y.
kim tra xem qun th c trng thi cn bng hay khng, trc
tin ta hy xem liu c bng chng no v s giao phi ngu nhin? Php
th u tin l xem tn s allele hai gii c ging nhau khng. Tnh ton
c th cho thy cc tn s gene hai gii khc nhau khng ng k.
- gii ci: f(B) = pc = (2277 ) + 54/( 2338 ) = 0,8994
f(O) = qc = (27 ) + 54/( 2338 ) = 0,1006
- gii c:
p = 311/353 = 0,881
T tn s cc allele gii ci, ta tnh c s c th k vng ca mi
kiu gene gii ny nh sau:
S c th
Quan st
K vng
2(1) = 4,6
Kiu gene
BB
277
273,2
P = 0,04
BO
54
61,2
Tng
OO
7
3,4
338
338
Kt qu cho thy cc s liu quan st khng ph hp lm vi s k

vng m ch yu l cc s liu thp (kiu BO v OO). Nu vy th s
khng nht qun c th l do giao phi ngu nhin, nhng cng c th
do th hiu ca con ngi thin v cc mu sc lm sai lch mu, khng
i din c cho qun th. Qua s phn tch ny cng vi s sai khc
cht t v tn s gene gia hai gii ni trn, chng ta chng c l do
g ngh rng qun th ny khng trng thi cn bng.
IV. Ni phi (inbreeding)

Bn cnh cc qun th giao phi ngu nhin xt, cn c cc ngoi l
i vi gi nh ny mt s loi, chng hn nh cc thc vt hoc ng
vt khng xng sng t th tinh. Ni phi l s giao phi khng ngu
nhin (nonrandom mating) xy ra gia cc c th c quan h h hng gn;
n c tm quan trng c bit ngi, bi v nhiu ngi mang cc bnh
di truyn ln sinh ra t s kt hn h hng. Hn na, ni phi c s
dng trong chn ging thc vt v c ng vt to ra cc dng mang
nhng c tnh mong mun no .
S giao phi khng ngu nhin i vi cc kiu gene xy ra trong cc
311
qun th, trong cc c th giao phi hoc l c quan h h hng gn

hn hoc l t gn hn so vi k vng giao phi ngu nhin t qun th.
Kt qu ca hai kiu giao phi ny c gi tng ng l ni phi
(inbreeding) v ngoi phi (outbreeding). Mc d c hai kiu giao phi
ny t n khng lm thay i tn s allele, nhng u lm thay i tn s
cc kiu gene ( mi locus trong b gene).
* Trong mt qun th ni phi, tn s ca cc th ng hp tng ln v
tn s ca cc th d hp gim xung so vi cc t l giao phi ngu nhin.
* Trong mt qun th ngoi phi, tnh hnh xy ra ngc li, vi tn s
cc th d hp tng v tn s cc th ng hp gim so vi cc t l giao
phi ngu nhin .
1. T th tinh (self-fertilization)
Kiu cc oan nht ca ni phi l s t th tinh, trong ht phn v
non (hay tinh trng v trng) c sinh ra trn cng mt c th. Hnh
thc sinh sn ny ph bin mt s nhm thc vt. Trong trng hp t
th tinh hon ton, mt qun th c phn thnh nhiu dng ni phi
mau chng tr nn ng hp cao . l trng hp cc dng u thun
chng c s dng bi Mendel.
Bng 12.6 S bin i tn s kiu gene trong mt qun th khi u vi ch
nhng th d hp t th tinh hon ton qua nhiu th h
Tn s kiu gene
Th h
0
1
2
...
n
AA
0
1/4
3/8
1 1/ 2n
2
1/2
Aa
1
1/2
1/4
1/2
0
Tn s allele
H s ni phi
aa
0
1/4
3/8
a
0,5
0,5
0,5
(F)_______
0
1/2
3/4
1 1/ 2n
2
0,5
11/2n
1/2
0,5
minh ha cho iu ny, ta gi s th h b m c ba kiu gene

AA, Aa v aa vi tn s tng ng l P, H v Q. Khi s t th phn l
hon ton, cc kiu gene AA v aa sinh ra i con tng ng ton l AA
v aa; cn kiu gene Aa theo quy lut phn ly Mendel s cho i con gm
mt na l Aa v na kia phn ng u cho hai kiu ng hp, AA v aa.
Khi tn s ca cc kiu gene AA, Aa v aa th h con tng ng l:
(P + H), (H) v (Q + H). Nh vy, sau mt th h t th tinh hon
312
ton, tn s th d hp gim i mt na so vi b m, trong khi tn s ca

hai kiu ng hp tng ln.
hiu r s ni phi lm thay i cc t l kiu gene ra sao, ta hy
xt qun th ban u gm ch nhng th d hp Aa khi t th tinh hon
ton qua nhiu th h (bng 12.6). V c sau mi th h mc d hp t li
gim i mt na so vi th h trc n, nn th h th n mc d hp
bng ()n ca tr s ban u: Hn = (n)H0, trong H0 v Hn l t l th d
hp th h ban u v th h th n. V t l mi kiu ng hp l (1n)/2. Khi n tin n v hn th thnh phn d hp b trit tiu v ch cn
li hai thnh phn ng hp vi tn s l . Lc ny, tn s mi kiu
gene bng tn s allele.
Mt im quan trng ca ni phi l ch, mc d cc tn s kiu
gene c th b thay i nhiu, nhng cc tn s allele vn c gi nguyn
khng i qua cc th h. Bn c th t chng minh iu ny?
2. H s ni phi (inbreeding coefficient )
m t hiu qu ca ni phi ln cc tn s kiu gene ni chung, ta
s dng php o gi l h s ni phi (F). Tr s ny c nh ngha l
xc xut m hai allele ti mt locus trong mt c th l ging nhau v
ngun gc (cc allele c coi l ging nhau v ngun gc khi hai allele
trong mt c th lng bi bt ngun t mt allele c th ca t tin).
Tnh cht ca h s ni phi (F):
+ Tr s F chy t 0 dn 1 (xem ct cui bng 12.6).
+ F = 1 khi tt c cc kiu gene trong qun th l ng hp cha
cc allele ging nhau v ngun gc.
+ F = 0 khi khng c cc allele ging nhau v ngun gc.
+ Trong mt qun th ngu phi c kch thc ln, F c coi l
gn bng 0, bi v bt k s ni phi no cng c th xy ra gia cc c
th h hng rt xa v v vy s c tc dng nh ln h s ni phi .
Gi s rng qun th gm ba kiu gene AA, Aa v aa c phn tch
thnh mt t l ni phi (F) v mt t l ngu phi (1 - F). Trong qun th
ni phi, tn s ca AA, Aa, v aa tng ng l p , 0, v q. y l t l
ca cc dng c k vng i vi mi kiu gene, nu nh s t th tinh
hon ton din ra lin tc. Bng cch cng cc t l ni phi v ngu phi
vi nhau v s dng mi quan h q = 1 p, lc tn s cc kiu gene tr
thnh nh sau (xem bng 12.7):
P = p2 + Fpq
H = 2pq 2Fpq
313
Q = q2 + Fpq
Trong mi phng trnh trn, s hng u l t l H-W ca cc kiu
gene v s hng sau l lch so vi tr s . Lu rng cc c th ng
hp, v d AA, c th hoc l do hai allele ging nhau v ngun gc, ngha
l bt ngun t cng mt allele t tin (s hng Fpq) hoc l do hai allele
ging nhau v loi sinh ra qua ngu phi (s hng p2). ln ca h s
ni phi phn nh lch ca cc kiu gene so vi cc t l H-W; ngha
l, lc F = 0 th cc hp t t t l H-W, v khi F > 0 do c ni phi, th
xy ra s gim thiu cc th d hp v di tha cc th ng hp.
Bng 12.7 Tn s ca cc kiu gene khc nhau khi trong qun th xy ra c
ni phi ln ngu phi
Kiu gene
Ni phi (F)
Ngu phi (1 F)
AA
Fp
(1 F)p2
Aa
(1 F)2pq
aa
Fq
F
(1 F)q2
1F
Tng
Fp + (1 F )p2 = p2 + Fpq
(1 F)2pq
= 2pq 2Fpq
Fq + (1 F)q2 = q2 + Fpq
1
1
3. Tnh ton h s ni phi

C hai cch c tnh h s ni phi, l da vo cc tn s kiu gene
hoc l da vo cc ph h.
Vi phng php th nht, ta c tnh h s ni phi trong mt qun
th t nhin bng cch s dng biu thc v tn s cc th d hp cho
trn. Qua ta c th tm ra biu thc cho F nh sau:
H = 2pq 2Fpq = (1 F)2pq
1 F = H/2pq
Suy ra F = 1 (H/2pq)
T phng trnh trn cho thy h s ni phi (F) l mt hm ca t s
gia mc d hp t quan st c (H) v mc d hp t k vng (2pq).
Trng hp c ni phi, H nh hn 2pq, v vy F > 0. Nu nh khng c
th d hp no c (H = 0), th h s ni phi bng 1.
Nhu loi thc vt c h thng giao phi bao gm c t th phn v
giao phn t do vi cc c th khc. Nu nh t l t th phn cao, th hu
nh tt c cc c th trong qun th l cc th ng hp. V d, mt qun
th thc vt gm ba kiu gene AA, Aa v aa vi cc tn s tng ng l P
= 0,70, H = 0,04 v Q = 0,26. Ta c th c tnh h s ni phi nh sau :
Trc tin, tnh c cc tn s allele A v a (p v q ):
314
p = 0,70 + (0,04) = 0,72 v q = 1 p = 0,28

Vy h s ni phi F = 1 ( 0,04/2 0,72 0,28 ) = 0,901
Tr s F y rt cao, gi rng hu ht qun th ny sinh sn bng t
th phn v ch mt s rt nh l tp giao.
Phng php th hai thu nhn h s ni phi cho i con l t
mt ph h trong c xy ra s giao phi cn huyt (consanguineous
mating). Trong trng hp ny ta s dng mt ph h tnh xc xut ca
cc t hp cha cc allele ging nhau v ngun gc i con. V d, ta
hy tnh h s ni phi cho mt i con ca hai anh ch em bn ng
huyt (half-sibs), tc cc c th sinh ra t cng mt b (hoc m). Hnh
12.1a cho ph h v kiu giao phi ny, trong X v Y l hai anh em c
cng m nhng khc cha. Ngi m ca X v Y c biu th l t tin
chung (CA = common ancestor). Cn hai ngi cha khng gp phn vo
h s ni phi c biu din bng cc hnh vung trng. hnh 12.1b,
cng mt ph h nh th nhng biu din theo mt cch khc, b qua cc
k hiu cha m cn cc du qu trm biu th cho tt c cc c th, v gii
tnh khng quan trng trong vic xc nh h s ni phi y. Cc mi
tn trn hnh v ch hng truyn t b m n con ci.
II
III
CA
CA
(a)
Y
Z
(b)
Y
Z
Hnh 12.1 Ph h minh ha s kt hn gia hai anh em bn ng huyt, X

v Y. (a) vi tt c cc c th; (b) khng c b. y CA = t tin chung, v
ng k i ch s giao phi cn huyt.
Gi s ngi m (CA) c kiu gene l Aa. tnh h s ni phi, ta

cn phi bit xc sut m a chu ca b, Z, c kiu gene AA hoc aa, l
ging nhau v ngun gc i vi mt trong hai allele ca b. Trc tin ta
xt Z l AA, ch c th xy ra nu nh mi bn X v Y u ng gp vo
Z mt giao t cha A. Xc sut ca allele A trong X l xc sut m mt
allele A n t CA, hay . V xc sut truyn t allele A t X sang Z
cng l , nn xc sut kt hp ca hai s kin ny l = (qui tc
nhn xc sut). Tng t, xc sut Z nhn c allele A t Y l . V
vy xc sut ca mt a con AA nhn c allele A t mi bn X v Y
315
l = 1/16 hay 0,0625. Bng phng php ny ta tnh c xc sut

ca mt a con c kiu gene aa l 1/16. Nh vy xc sut ton b cc t
hp c cha cc allele ging nhau v ngun gc Z lc l 1/16 + 1/16
= 1/8 hay 0,125 (qui tc cng xc sut ).
n gin, trong tnh ton h s ni phi t mt ph h ngi ta
xut mt phng php gi l k thut m chui (chain-counting
technique). Mt chui i vi mt t tin chung cho trc bt u vi mt
b m ca c th ni phi, ngc tr ln ph h cho n t tin chung, v
tr li vi b m . V d, t hnh 12.1 ta lp c chui n gin X-CAY. S c th trong chui (n) c dng tnh h s ni phi trong cng
thc sau y: F = (1/2)n. Vi v d trn, h s ni phi l (1/2)3 = 0,125.
V. Cc nhn t tc ng ln thnh phn di truyn qun th

Trong t nhin, thnh phn di truyn ca cc qun th ni chung l
khng n nh nh nguyn l Hardy-Weinberg vch ra, m lun lun b
bin ng di nh hng ca nhiu nhn t khc nhau. Ln u tin, vn
ny c Charles Darwin nu ln trong tc phm Ngun gc cc loi
bng con ng chn lc t nhin (On the Origin of Species by Means of
Natural Selection) nm 1859. Theo quan nim hin nay, c bn nhn t c
bn lm thay i tn s cc allele ca cc qun th v xc nh qu trnh
tin ha, l: t bin, bin ng di truyn ngu nhin, di-nhp c v
chn lc t nhin. V chi tit, c th xem thm trong Bi ging Di truyn
hc qun th (Hong Trng Phn 2003); y chng ta ch tm hiu s
lc vai tr v hiu qu ca mi nhn t.
1. t bin
t bin (mutation) c nhiu loi khc nhau nh c trnh by
cc chng 3 v 8; y chng ta ch cp n vai tr, tnh cht v p
lc ca cc t bin gene t pht i vi qu trnh tin ha v chn lc.
Phn ln t bin mi xut hin c hi cho c th
t bin l ngun cung cp ch yu cc bin d di truyn mi trong
mt qun th-loi, v vy n c xem l mt qu trnh quan trng c
bit trong di truyn hc qun th. Ni chung, phn ln t bin mi xut
hin l c hi, mt s t bin l trung tnh v ch mt s t l c li cho
bn thn sinh vt. Theo thuyt trung tnh (Kimura 1983), i a s cc
bin i tin ha cp phn t c gy nn khng phi bng chn lc
Darwin m bng s c nh ngu nhin cc th t bin trung tnh hoc
hu nh trung tnh v mt chn lc; p lc t bin v bin ng di truyn
ngu nhin chim u th trong s bin i tin ha cp phn t.
xt xem hiu qu ca t bin ln s bin i di truyn trong mt
316
qun th, ta xt hai allele A (kiu di) v a (gy hi) vi tn s ban u

tng ng l p v q; gi u l t l t bin thun t A thnh a cho mt giao
t mi th h, v v l t l t bin nghch t a thnh A. Cc allele A do
t bin thun thnh a lm tng tn s ca allele a ln mt lng l up,
trong khi tn s alllele a do t bin nghch c th b gim i mt lng
l vq. Nh vy, nhn ton cc th sau mi th h s bin i trong tn s
ca allele a (q) do t bin l:
q = up vq
Tr s dng cc i cho s bin i ny l u, khi p = 1 v q = 0 (ngha l
tt c cc allele u l kiu di). Tr s m cc i l v, khi p = 0 v q = 1.
Tuy nhin do cc t l t bin u v v ni chung l nh, nn s bin i
c k vng do t bin cng rt nh. Chng hn, nu ta cho u = 10-5, v
= 10-6 v q = 0,0, lc :
q = (0,00001)(1,0) (0,000001)(0,0) = 0,00001
Mc d t bin ch gy mt hiu qu nh trong tn s allele mi th
h, nhng n li c tm quan trng cn bn trong vic xc nh mc
gy ra cc bnh di truyn him. Trn thc t, s cn bng gia t bin
(lm tng tn s ca allele bnh) v chn lc (lm gim tn s ca allele
bnh) c th l gii mc quan st c ca cc bnh nh bch tng
chng hn. Ngoi ra, t bin cng vi s bin ng di truyn ngu nhin
cho php gii thch hp l cho s lng ln cc bin i phn t quan st
c gn y nhiu loi (xem Kimura 1983).
2. Bin ng di truyn ngu nhin
Bin ng di truyn ngu nhin (genetic random drift), hay ni gn l
bin ng di truyn, l nhng s bin i ngu nhin v hng v tn
s allele trong tt c cc qun th, nhng c bit l cc qun th nh.
Bin ng di truyn l mt qu trnh thun ty ngu nhin, mang tnh
xc sut v t l nghch vi kch thc qun th. Trong mt qun th ln,
thng thng bin ng di truyn ch gy ra mt s thay i ngu nhin
nh. Nhng trong cc qun th nh, n c th gy ra nhng s bin ng
ln v tn s allele qua cc th h khc nhau. Chnh hin tng ny l
nguyn nhn to nn s khc bit a dng v mt di truyn cc qun th
nh v dn dn dn ti s cch ly sinh sn trong qu trnh tin ha ca
loi. V s bin ng di truyn c th l nguyn nhn lm cho mc d hp
t thp quan st c mt s loi c nguy c b dit vong.
3. Dng gene hay s di nhp c
Di-nhp c (migration) hay dng gene (gene flow) l s di chuyn ca
cc c th t mt qun th ny sang mt qun th khc, ko theo vic a
317
vo cc allele nhp c mi thng qua s giao phi v sinh sn sau .

Nh vy, dng gene khng lm thay i cc tn s allele ca c loi,
nhng c th lm bin i cc b (tn s allele so vi nguyn l H-W) khi
tn s cc allele ca nhng c th di c ti l khc vi ca cc c th c
tr ti ch. Gi s cc c th t cc qun th xung quanh di c ti mt
qun th a phng ta nghin cu vi tc m mi th h v giao phi
vi cc c th c tr . V cng gi s rng tn s allele A ca qun th
ngun gene nhp c l P v ca qun th nghin cu l po. Khi , th
h th nht sau nhp c, tn s allele A ca qun th nghin cu s l:
p1 = (1 m)po + mP = po m(po P)
S bin i p v tn s allele sau mt th h l: p = p1 po
Thay tr s p1 thu c trn, ta c: p = m(po P)
iu c ngha l, t l cc c th di c cng ln v s chnh lch
gia hai tn s allele cng ln, th i lng p cng ln. Lu rng p =
0 ch khi hoc m = 0 hoc (po P) = 0. Nh vy, tr phi s di c dng li
(m = 0) cn th tn s allele s tip tc bin i cho n khi n tr nn
ging nhau gia qun th a phng v qun th ph cn (po P = 0).
Sau th h th nht, hiu s v tn s allele gia hai qun th trn l:
p1 P = po m(po P) P
= (1 m)(po P)
Tng t, sau th h th hai, hiu s v tn s allele s l:
p2 P = (1 m)2.(po P)
V sau n th h di c, ta c:
pn P = (1 m)n.(po P)
Cng thc ny cho php ta tnh ton hiu qu ca n th h di c tc
m no , nu nh bit c tn s cc allele khi u (po v P):
pn = (1 m)n.(po P) + P
Hoc nu nh bit c tn s cc allele khi u (po v P), tn s allele
ca qun th nghin cu ti mt thi im no (pn) cng nh s th h
n, ta c th tnh c tc dng gene (m).
V d: M (USA), nhng ngi c ngun gc hn chng da trng
Capca (Caucasian) v da en Chu Phi (African) c coi l thuc qun
th ngi da en. S pha tp v chng tc c th xem nh l mt qu trnh
ca dng gene t qun th Capca sang qun th da en. Tn s ca allele
Ro locus xc nh cc nhm mu rhesus l P = 0,028 cc qun th
Capca nc M. Trong s cc qun th Chu Phi m t cc t tin ca
318
ngi M da en di c n, tn s allele Ro l 0,630. T tin Chu Phi ca

nhng ngi M da en n nc M cch y khong 300 nm hay
khong 10 th h; ngha l n = 10. Tn s allele Ro trong s nhng ngi
M hin gi l pn = 0,446.
Bng cch bin i li phng trnh trn, ta c:
(1 m)n = (pn P) : (po P)
Thay cc tr s cho, ta c:
(1 m)10 = (0,446 0,028) : (0,630 0,028) = 0,694
1m=
10
0,694 = 0,964
Suy ra:
m = 0,036
Nh vy, dng gene chuyn t nhng ngi M Capca vo trong qun
th ngi M da en xy ra tc tng ng vi tr s trung bnh
l 3,6% mi th h. Nhng tnh ton tng t bng cch s dng cc tn
s allele nhiu locus khc cho cc kt qu hi khc mt cht. Hn na,
mc pha tp hn chng c th khc nhau cc vng khc nhau ca
nc M; nhng r rng l s trao i gene ng k xy ra (Ayala v
Kiger 1980, tr.644; Hartl et al 1988, tr.214).
4. Chn lc t nhin
C ba qu trnh gy bin i tn s gene xt trn y u c mt
im chung l khng mt qu trnh no nh hng i vi s thch nghi
(adaptation). Theo nhn nh ca mt s tc gi (Mayer 1974; Ayala v
Kiger 1980), cc qu trnh ny l ngu nhin i vi s thch nghi, do
t thn chng s ph hoi t chc v cc c tnh thch nghi ca sinh vt.
Ch c chn lc t nhin (natural selection) mi l qu trnh thc y s
thch nghi v hn ch cc hiu qu ph hoi t chc ca cc qu trnh
khc. Trong ngha , chn lc t nhin l qu trnh tin ha khc lit
nht, bi v ch c n mi c th gii thch c bn cht thch nghi, tnh
a dng (diversity) v c t chc cao ca cc sinh vt.
tng v chn lc t nhin nh l qu trnh nn tng, l ng lc
ca s bin i tin ha do Charles Darwin v Alfred Russel Wallace c
lp a ra nm 1858. L lun tin ha bng chn lc t nhin c
pht trin y , vi chng c ng h xc ng, trong cun Ngun gc
cc loi (The Origin of Species) do Darwin xut bn nm 1859.
Theo Hartl et al (1988, 1997), trn quan im thuyt tng hp hin
i, c th hnh dung chn lc t nhin xy ra da trn ba im chnh: (1)
mi sinh vt, i con c sinh ra nhiu hn s sng st v sinh sn; (2)
Cc c th khc nhau v kh nng sng st v sinh sn v phn ln nhng
319
khc bit ny l do kiu gene; (3) Trong mi th h, cc kiu gene sng

st s sinh sn nhiu hn v quyt nh s phn b li cc kiu gene th
h sau. Hu qu l, cc allele tng cng s sng st v sinh sn s gia
tng tn s t th h ny sang th h khc, v qun th s ngy cng
sng st v sinh sn tt hn vi mi trng ca n.
Trn quan im , chn lc t nhin c nh ngha l s sng st
v sinh sn bit ha ca cc kiu gene.
hiu c cc tc dng ca chn lc ln bin d di truyn, ta phi
xt xem ph hp tng i (relative fitness) ca cc kiu gene khc
nhau. N c nhiu thut ng ng ngha nh: ph hp Darwin
(Darwinian fitness), gi tr chn lc (selective value), hay gi tr thch
nghi (adaptive value). Tu trung, n c th c nh ngha nh l kh
nng tng i ca cc kiu gene khc nhau trong vic truyn li cc
allele cho nhng th h tng lai (Weaver v Hedrick 1997).
Bi v chn lc t nhin tc ng bng s sinh sn bit ha, nn ta c
th xem n l s o hiu nng sinh sn ca mt kiu gene. cho tin, cc
nh di truyn hc thng t nh tr s ph hp (w) bng 1 cho kiu
gene c hiu nng sinh sn cao nht. Mt n v o lin quan l h s
chn lc (selection coefficient), c k hiy bng s, v c nh ngha
l s = 1 w. H s chn lc o mc gim bt ph hp ca mt kiu
gene. Gi s mi th h cc kiu gene AA v Aa u sinh c 100 con,
cn th ng hp ln sinh c 80 con; nu ta coi ph hp ca cc c
th mang allele tri l 1, th ph hp ca cc th ng hp ln l 0,8.
Hiu s ca cc tr s ph hp ny chnh l h s chn lc (s), v trong
trng hp ny s = 1 0,8 = 0,2. Nu nh cc kiu gene c kh nng sng
st v sinh sn nh nhau th s = 0; nu mt kiu gene no gy cht hoc
lm bt th hon ton th s = 1.
4.1. Chn lc v t bin
Chn lc c xu hng o thi cc allele c hi ra khi qun th, trong
khi t bin c th to ra cc allele c hi mi. Qun th s gi nguyn
trng thi phn b cc kiu gene nu nh tn s t bin mi xut hin
va ng bng tn s allele b chn lc o thi. Sau y ta th xt s cn
bng ny trong trng hp "Chn lc chng li cc ng hp t ln".
Gi s A l allele bnh thng v a l allele c hi vi tn s tng
ng ca chng l p v q. Khi ph hp hay gi tr thch nghi ca cc
kiu gene AA, Aa v aa tng ng l 1: 1: 1-s. Trong trng hp ny tc
o thi allele a khi qun th bi chn lc s l sq2. Nu cho rng tc
t bin thun (A a) l u, th tc xut hin allele a mi trong qun
th l up. V p 1 (do tn s a rt thp) nn c th coi up u. Vi c ch
320
ngu phi, qun th s trng thi cn bng khi tc xut hin t bin
mi bng tc o thi, ngha l u = sq2, hay khi tn s allele ln trong
qun th mc q = u / s . Tng t, i vi allele tri, u = sp hay p = u/s.
V d: Tn s mc bnh PKU tr s sinh l khang 4 trn 100.000;
do q2 = 410-5. Hiu qu sinh sn ca cc bnh nhn khng c cha
tr l zero, hay s = 1. Khi u = sq2 = 4 10-5.
4 x10 5 = 6,310-3
v tn s ca cc th d hp l: 2pq 2q = 2(6,310-3) = 1,2610-2
iu c ngha l, trong 100 ngi c khong 1,3 ngi mang allele ,
mc d c 4 trong 100.000 ngi mc bnh PKU. Tn s ca allele ny c
mt trong cc th d hp bng mt na ca 1,2610-2 hay 6,310-3; v tn
s ca allele cc th ng hp l 4 10-5. Do vy cc allele PKU c
mt trong cc th d hp nhiu hn 6,310-3 / 4 10-5 = 158 ln so vi cc
th ng hp. Nh ni t u, cc allele him tn ti trong qun th hu
ht cc th d hp.
4.2. u th d hp t
u th d hp t hay siu tri (overdominance) l trng hp chn lc
u i ng h cc th d hp nhiu hn c hai dng ng hp t. Khi
chn lc khng loi thi allele no. mi th h, cc th d hp s sinh
sn mnh cho nhiu con chu hn cc th ng hp v chn lc s gi li
c hai allele cho n khi qun th to c trng thi cn bng, vi cc tn
s allele khng thay i.
Mt v d ni bt v hin tng siu tri trong cc qun th ngi l
bnh thiu mu hng cu hnh lim, mt bnh ph bin chu Phi v chu
. Bnh ny c lin quan n mt dng st rt do k sinh trng ph bin
gy ra l Plasmodium falciparum. Allele HbS gy cht trc tui trng
thnh nhng ngi ng hp t HbSHbS. Tn s allele ny c th cao
hn 10% cc vng c st rt ni trn, bi v cc th d hp HbAHbS
khng c s nhim st rt, trong khi cc th ng hp HbAHbA th
khng c kh nng .
Tn s allele ny trong cc qun th ngi l q =
Cu hi v Bi tp
1. (a) nh ngha cc khi nim sau: di truyn hc qun th, qun th,
vn gene, tn s allele v tn s kiu gene. (b) c trng di truyn ca cc
qun th giao phi v ni phi l g?
2. Ti sao ni khi nim cn bn v cng c thit yu ca di truyn hc
321
qun th l tn s allele ch khng phi tn s kiu gene? Hy thit lp

cc cng thc tnh tn s allele khc nhau v cho v d.
3. (a) Nu ni dung v cc iu kin nghim ng ca nguyn l
Hardy-Weinberg. T hy chng minh v nu cc h qu v ng dng
ca n. (b) Th no l trng thi cn bng di truyn ca qun th? Cc
phng php kho st trng thi cn bng di truyn ca qun th?
4. Nguyn l Hardy-Weinberg c m rng cho cc trng hp a
allele, tn s allele sai khc gia hai gii tnh v cc gene lin kt vi gii
tnh nh th no?
5. Hy tnh tn s cc allele v kho st trng thi cn bng theo cc
cch khc nhau i vi h nhm mu M-N cc qun th ngi sau y
(s liu t F.J. Ayala v J.A. Kiger 1980):
Qun th
MN
Tng
Th dn c
22
216
492
730
B lc da Navaho
305
52
4
361
Ngi M gc Capca 1787
3039
1303
6129
6. Hy tnh tn s allele trong cc trng hp sau:
a) Cc th ng hp ln nhiu gp hai ln cc th d hp.
b) Cc th ng hp ln nhiu gp su ln cc th d hp.
7. Mu sc v c sn chu u c kim sot bi ba allele mt locus
n: CB (nu), CP (hng) v CY (vng). Allele mu nu l tri so vi hng
v vng; mu hng tri so vi vng; mu vng l ln hon ton. Trong mt
qun th c sn cc mu sc c phn b nh sau: 472 nu, 462 hng, 66
vng. Nu nh qun th ny dng cn bng, tn s cc allele s ra sao?
8. Chng m mu do mt allele ln m lin kt trn X gy ra. C mi
ngi c mt ngi nam mc chng m mu. Hi: (a) T l n gii
l bao nhiu? (b) Nu mt na s tr sinh ra mi gii tnh b m mu, th
t l cc cuc hn nhn gy ra hu qu l bao nhiu? (c) Nu nh tt c
tr sinh ra u bnh thng, th t l cc cuc hn nhn l nh th no?
9. Chng minh rng khi mt qun th tin ti trng thi cn bng i
vi mt gene lin kt gii tnh, th: (a) S dao ng v tn s allele gia
hai gii thu hp dn sau mi th h theo quy lut sau: (pc p) = (pc
p) , trong pc v p l cc tn s gene tng ng ca hai gii ci v
c i b m, cn pc v p l cc tn s tng ng i con ca n.
(b) Tn s gene ca c qun th ( p ) l khng i qua cc th h v bng
pc + p.
322
10. (a) mt qun th sinh vt, tn s ca cc th ng hp tri, d

hp v ng hp ln tng ng l 0,67; 0,06 v 0,27. H s ni phi l
bao nhiu? (b) Nu nh trong mt qun th vi hai allele mt locus
nhim sc th thng c p = 0,8, q = 0,2, v tn s ca cc th d hp l
0,20, th h s ni phi l bao nhiu?
Ti liu Tham kho

Ting Vit
Trn B Honh. 1988. Hc thuyt tin ha. NXB Gio Dc, H Ni.
Kimura M. 1983. Thuyt tin ha phn t trung tnh (Bn dch ca Hong
Trng Phn). NXB Thun Ha, Hu -1993.
Mayer E. 1974. Qun th, loi v tin ha. (Bn dch ca Lng Ngc
Ton, Hong c Nhun, Nguyn c Khm v Nhuyn Vn Tho).
Hong Trng Phn. 2001. H qu ca mt s nh lut di truyn v ng
dng ca chng trong ging dy di truyn hc. Trong: K yu Hi ngh
Khoa hc Khoa Sinh-KTNN, Trng HSP H Ni, tr.5-8.
Hong Trng Phn. 2003. Di truyn hc qun th (Bi ging lu hnh ni
b). Trng HSP Hu.
Ting Anh
Ayala FJ, Kiger JA. 1980. Modern Genetics. Benjamin/Cummings
Crow JF. 1986. Basic Concepts in Population, Quantitative, and
Evolutionary Genetics. WH Freeman and Co., New York.
Crow JF. 1993. Mutation, mean fitness, and genetic load. In: Oxford in
Evolutionary Biology, Volume 9 (Futuyma D., Antonovics J. eds), pp 3-42,
Oxford University Press, Inc., Oxford -New York...
Falconer DS, Mackay TFC. 1996. Introduction to Quantitative Genetics.
4th ed., Longman Group, Harlow.
Bartlett Publishers, Inc., Boston - Portola Valley.
Hartl DL, Clark AG. 1997. Principles of Population Genetics. 3rd ed.,
Sinauer Associates Inc., Sunderland, Massachusets. ISBN: 0-87893-306-9.
Holman DJ. 2003. Human Population Genetics BIO A 482 Autumn
2003). <http://faculty.washington.edu/djholman/bioa482/>
Ridley M. 1993. Evolution. Blackwell Scientific Publishing, Boston.
323
Standfield WD. 2002. Genetics, 4th ed. Schaum's Outline Series.

McGraw-Hill Inc., Toronto.
to Genetic Analysis. 4th ed., W-H Freeman and Company, New York.
Yablokov V.A. 1986. Population Biology: Progress and Problems on
Natural Populations. Mir Publishers, Moscow.
Weaver RF, Hedrick PW. 1997. Genetics. 3rd ed., McGraw-Hill
Companies, Inc./ Wm.C.Browm Publishers, Dubuque, IA.
Wrights 1988. Surfaces of selective value revisited. The American
Naturalist 131: 115-123.
Mt s trang web
http://wbar.uta.edu/jands/jands.htm
http://science.kennesaw.edu/~rmatson/Biol%203380/3380species.html
http://www.users.nac.net/jmele/ECO.HW.html
http://nitro.biosci.arizona.edu/courses/EEB182/Lecture04/lect4.html

Đại học Y Dược Huế 2005 = Di Truyền Học Đại Cương

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Đại học Y Dược Huế 2005 = Di Truyền Học Đại Cương

Uploaded by

Copyright:

Available Formats

GIO TRNH

ThS. Hong Trng Phn (ch bin)

I. Khi nim di truyn hc

Chng 1: C s ca Di truyn hc Mendel

I. Tiu s Mendel - Cha ca di truyn hc

Chng 2: M rng v p dng ca Di truyn hc

I. Cc kiu quan h gia cc gene allele i vi mt tnh trng

Chng 3: C s T bo ca s Sinh sn, Di truyn

I. Sinh sn hu tnh v tnh n nh ca cc b nhim sc th

Chng 4: Di truyn hc Nhim sc th

I. Trng phi Morgan vi thuyt di truyn nhim sc th

Chng 5: Bn cht Ho hc v Ti bn ca Vt cht

I. Bng chng vt cht di truyn l cc nucleic acid

2. Cu trc chui polynucleotide

Chng 6: Gene v Qu trnh Sinh tng hp Protein

I. S pht trin ca khi nim gene

Chng 7: S iu ho Biu hin ca Gene

I. Cc nguyn l iu ho v mc kim sot phin m

Chng 8: t bin Gene, Ti t hp v cc Yu t

Chng 9: S Di truyn T bo cht

Trng Th Bch Phng 245

Chng 10: i cng v Cng ngh DNA Ti t hp

I. Cc cng c chnh ca k thut to dng DNA ti t hp

III. Cc phng php biu hin cc gene c to dng

Chng 11: Di truyn hc Ngi

I. Cc phng php nghin cu di truyn hc ngi

Chng 12: Di truyn hc Qun th

I. Cc khi nim c bn ca di truyn hc qun th

3. Vn gene (gene pool)

II. Lc s pht trin ca di truyn hc

Trong nhng nm u th k XX, nh ng dng di truyn Mendel,

to thnh nhm lin kt. Nhng ng gp ng k ca cc mn xut

3. S ra i v pht trin ca di truyn hc phn t

tng nghin cu ch yu l cc vi sinh vt. Tuy nhin, trc Friedrich

Hnh 4 Beadle, Tatum, Jacob v Monod (t tri sang)

V mi quan h gia gene v protein, t 1902 Archibald Garrod qua

Vic nghin cu cu trc phn t

Hnh 6 R.Franklin (tri) v M.Wilkins

xon kp (double helix). Pht minh v

l mt bi bo khng bnh thng. Ch vn vn c 128 dng nhng ng

di truyn ny c hon thnh vo thng 6 nm 1966 bi hai nhm nghin

Hnh 9 Cc nh khoa hc ot gii Nobel y hc lin quan k thut gene.

Hnh 10 Cc nh khoa hc ot gii Nobel ha hc lin quan k thut

v Frederick Sanger (gii Nobel ha hc 1980; Hnh 10); s khm ph ra

III. i tng v cc lnh vc nghin cu ca di truyn hc

ny ko di t thi Mendel cho n thp nin 1940, vi c trng l

IV. Cc phng php nghin cu ca di truyn hc

chc ca cc gene v b gene, cc c ch iu ha v bin i di truyn

(5) Di truyn hc l mt khoa hc thc nghim, nn thng tin thu

l v cng to ln, gp phn to nn cuc "cch mng xanh ln th hai" vi

Ti liu Tham kho

I. Tiu s Mendel - Cha ca Di truyn hc

Khi cn trang tri ca cha mnh, Mendel quan tm ti cc cy ci

hiu c cc pht hin ca ng, c l mt phn l do ng s dng ton

II. i tng v phng php th nghim ca Mendel

Mendel chn u H Lan (Pisum sativum) lm i tng nghin cu

III. Lai mt tnh v nguyn l phn ly

T tt c cc php lai trn cho thy: Khi b m th h xut pht (P)

ln tt c u l cc cy ln thun chng; iu c ngha l tt c con ci

Hnh 1.3 S biu din kt qu lai mt tnh ca Mendel.

Trong gim phn, mi b m thun chng ht vng (AA) v ht xanh

F1 u c kiu hnh tri ht vng. Khi bc vo gim phn, cc c th F1

Ni dung chnh ca nguyn l hay quy lut phn ly c th tm lc

IV. Lai hai tnh v nguyn l phn ly c lp