Bai Giang Di Truyen - Truong Thi Bich Phuong

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MC LC
Chng 1. Bn cht ca vt cht di truyn............................................ 1 I. DNA l vt cht di truyn...................................................................1 1. Cc chng minh gin tip .................................................................1 2. Th nghim bin np DNA ( Transformation)................................... 2 3. S xm nhp ca DNA virus vo vi khun........................................ 4 II. Thnh phn v cu to ha hc ca acid nucleic.............................. 5 1. DNA................................................................................................... 7 1.1. Cu to ha hc ca DNA.............................................................. 7 1.2. DNA cun li trong t bo .......................................................... 11 2. RNA .................................................................................................14 2.1. RNA riboxom (ribosomal RNA-rRNA)....................................... 14 2.2. RNA vn chuyn (Transfer RNA - tRNA)................................... 15 2.3. RNA thng tin (messenger RNA mRNA)................................. 17 2.4. Ribozym v self-splicing.............................................................. 18 III Cc tnh cht ca DNA................................................................... 20 1. Bin tnh (denaturation) v hi tnh (renaturation)........................ 20 2. Lai acid nucleic............................................................................... 22 IV. Nhng cu trc cha DNA trong t bo........................................ 23
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1. Nhng on DNA cha thng tin di truyn.....................................23 2. Virus cha DNA v virus cha RNA............................................... 24 3. Nhim sc th chnh v plasmid ca vi khun.................................25 4. Nhim sc th Eukaryota.................................................................25 4.1 Cc trnh t lp li v n c....................................................... 25 4.2 Nhim sc th ca Eukaryota.........................................................27 4.3 Trnh t CEN................................................................................. 29 4.4. Trnh t Tel................................................................................... 29 Cu hi n tp .................................................................................... 30 Ti liu tham kho .............................................................................. 30 Chng 2. Sao chp DNA................................................................... 31 I. S bn vng ca DNA vi thi gian v qua nhiu th h................ 31 1. DNA b bin i ngay c khng sao chp .......................................31 2. Trnh t nucleotid c duy tr vi mc chnh xc rt cao qua nhiu th h................................................................................................... 32 3. Cc h thng bo v DNA............................................................... 33 4. Sa sai do phc quang hi.............................................................. 34 5. H thng SOS.................................................................................. 35 II. C ch phn t ca sao chp DNA ................................................ 36 1. Nguyn tc chung............................................................................ 36 2. Th nghim tng hp nhn to DNA................................................37 3. Th nghim chng minh c s t nhn i theo nguyn tc bn bo tn........................................................................................................ 37
4. Din bin sao chp DNA nhim sc th E.coli.............................38 4.1. Giai on khi s (initiation)........................................................38 4.2. Giai on ni di (elongation)...................................................... 39 III. Sao chp DNA trong t bo........................................................... 40 1. Sao chp nhim sc th Prokaryote............................................. 40 2. Sao chp nhim sc th t bo Eukaryote.................................... 41 Cu hi n tp .................................................................................... 42 Ti liu tham kho .............................................................................. 42 Chng 3. C s t bo hc ca tnh di truyn....................................44 I. Cc cu trc t bo v kh nng t ti sinh...................................... 44 1. Cc cu trc c kh nng t ti sinh...............................................44 2. Nhim sc th.................................................................................. 45 2.1. Hnh thi NST............................................................................... 45 2.2. Kiu nhn v nhim sc :.......................................................... 47 2.3. Cht nhim sc..............................................................................47 3. Cc nhim sc th c bit.............................................................. 48 II. Chu trnh t bo v phn bo Eukaryote...................................... 51 1. Chu trnh t bo...............................................................................51 2. Nguyn phn (Mitosis) ....................................................................52 3. Gim phn (meiosis)........................................................................53 III. Cc kiu sinh sn........................................................................... 59
1.Sinh sn v tnh................................................................................ 59 2. Sinh sn hu tnh............................................................................. 59 3. Cc hnh thc sinh sn c bit.......................................................61 4. Chu trnh sng hay vng i........................................................... 63 Cu hi n tp .................................................................................... 64 Ti liu tham kho .............................................................................. 64 Chng 4. Cc quy lut di truyn ca Mendel.................................... 66 I. Phng php th nghim ca Mendel............................................... 66 1. Tnh trng hay du hiu (character)............................................... 66 2. Cch tin hnh th nghim:............................................................. 68 II. Lai mt tnh trng-Quy lut giao t thun khit..............................69 1.Th nghim........................................................................................ 69 2. Gii thch ca Mendel..................................................................... 70 3.Tnh tri khng hon ton v s di truyn tng ng..................70 4. C s t bo hc.............................................................................. 70 5. Th nghim chng minh trc tip s phn ly mc giao t .......... 72 6. Quy lut th nht (quy lut giao t thun khit.............................. 72 III. Lai hai tnh v nhiu tnh............................................................... 73 1. Lai hai tnh - Quy lut phn ly c lp v t hp t do.................. 73 2. Lai vi nhiu cp tnh trng........................................................... 73 3. Mt s tnh trng Mendel ngi...................................................75
4. Cc quy lut chung ca tnh di truyn.............................................77 Cu hi n tp .................................................................................... 77 Ti liu tham kho .............................................................................. 78 Chng 5. Tng tac gen.................................................................... 79 I. S tng tc gen gia cc gen alen................................................. 79 1. Hin tng gy cht........................................................................ 79 2. S tng tc gia cc alen ca cng mt gen.................................82 II. S tng tc gia cc gen khng alen.............................................83 1. Tng tc t ch.............................................................................. 83 3. Tng tc a gen............................................................................. 88 4. Tnh a hiu ca gen....................................................................... 89 III. Nhng phc tp trong biu hin cu gen....................................... 89 1. Gen bin i (Modifier gene).......................................................... 89 2. Cc tnh trng b gii hn bi gii tnh.......................................... 90 3. Cc tnh trng c s biu hin ph thuc vo gii tnh.................. 90 IV thm (penetrance) v biu hin (expression)....................... 91 1. thm ( thm nhp)..................................................................91 2. hin hay biu hin ................................................................92 V. Tc ng ca mi trng................................................................ 93 1. Tc ng ca mi trng bn ngoi............................................... 93 2. Tc ng ca mi trng bn trong................................................ 94
Cu hi n tp .................................................................................... 95 Ti liu tham kho .............................................................................. 95 Chng 6. Hc thuyt di truyn nhim sc th....................................96 I. S xc nh gii tnh v s di truyn lin kt vi gii tnh.............. 96 1. T l phn li gii tnh....................................................................... 96 2. Cc gen lin kt vi gii tnh...........................................................98 3. Cc tnh trng lin kt vi gii tnh trong di truyn hc ngi... 101 4. Gen nam gii v gen n gii ngi............................................101 4.1. Gen xc nh nam gii................................................................ 101 4.2. Gen xc nh n gii...................................................................102 5. NST X bt hot ngi................................................................. 102 6. Hin tng khng chia ly ca NST................................................104 7. Xc nh gii tnh do s bi th.....................................................106 8. Xc nh gii tnh do iu kin mi trng ..................................106 II. S di truyn lin kt...................................................................... 107 1. Hin tng lin kt........................................................................ 107 2. Lin kt hon ton......................................................................... 108 3. Hin tng di truyn lin kt khng hon ton............................. 108 4. Cc nhm lin kt(Genelinkage)................................................... 109 III. Hin tng ti t hp................................................................... 109 1. Ti t hp v trao i cho........................................................... 109
2. C s t bo hc ca trao i cho...............................................111 3. Trao i cho trong giai on 4 si...........................................112 4. Trao i cho nhiu ln.................................................................114 5. Nhiu (Interference) v trng hp (Coincidence) ........................ 114 IV. Xc nh v tr gen v bn di truyn....................................... 115 1.Xc nh vi tr gen.......................................................................... 115 2. Bn di truyn ca NST v bn di truyn t bo...................116 V. NST ngi v bn NST ngi................................................ 119 1. NST ngi......................................................................................119 2. K thut lai t bo soma................................................................ 120 Cu hi n tp .................................................................................. 122 Ti liu tham kho ............................................................................ 122 Chng 7. Di truyn hc Vi khun................................................... 123 I. u th v cc c im ca i tng vi sinh vt .........................123 1. Thi gian th h ngn, tc sinh sn nhanh...............................123 2. C s tng vt s lng c th...................................................... 123 3. C cu to b my di truyn n gin.......................................... 124 4. D nghin cu bng cc k thut vt l v ha hc...................... 124 II. c im ca di truyn vi sinh vt................................................124 III. Sinh hc ca vi khun.................................................................. 125 1. Cu to t bo v sinh sn............................................................ 125
2. c im nui cy......................................................................... 127 IV. Bin np ( Transformation)......................................................... 127 1. Hin tng v iu kin.................................................................127 2. C ch bin np.............................................................................128 2.1. Xm nhp ca DNA....................................................................128 2.2. Bt cp........................................................................................ 130 2.3. Sao chp...................................................................................... 130 V. Ti np (Transduction)..................................................................130 1. Phage l nhn t chuyn gen.........................................................130 2. c ch.............................................................................................131 3. Phn bit cc dng ti np............................................................ 132 VI. Giao np (Conjugation)............................................................... 133 1. Chng minh c lai vi khun....................................................... 134 2. S phn ha gii tnh vi khun...................................................135 3. Cc nhn t F' v tnh np (Sexduction)....................................... 137 4. C ch ti t hp .......................................................................... 137 VII. C s di truyn tnh khng thuc ca cc vi khun gy bnh ngi.................................................................................................. 139 Cu hi v Bi tp..............................................................................140 Ti liu Tham kho............................................................................140 Chng 8. Di truyn hc Virus......................................................... 142 I. Di truyn hc th thc khun (Bacteriophage hay phage)............. 142
1. S hnh thnh vt tan v cc th t bin phage...........................142 2. Ti t hp di truyn trong mt chu k sinh tan (Lytic cycle)........ 144 2.1. Chu trnh tan (Lytic cycle)..........................................................144 3. S sp xp ca cc gene trong nhim sc th phage.................... 146 4. Lp bn cu trc tinh vi vng rII ca phage T4.......................147 5. Tnh tim tan (Lysogeny) v phage ............................................ 151 II. c tnh ca cc virus................................................................... 153 1. Tnh a dng v cu trc v thnh phn di truyn....................... 153 2. Tnh c th v vt ch (Host specificity)..................................... 154 III. Ti bn ca cc virus................................................................... 154 1. Cc virus ca vi khun.................................................................. 157 2. Cc virus thc vt......................................................................... 157 3. Cc virus ng vt........................................................................ 158 4. Virus gy ung th, HIV/ AIDS.......................................................160 Cu hi v Bi tp............................................................................. 163 Ti liu Tham kho............................................................................ 163 Chng 9. Di truyn hc Vi nm v Vi to.......................................165 I. i cng v nghin cu di truyn mt s vi to thng dng.... 165 II. Phn tch di truyn vi nm......................................................... 166 1. Tnh khng dung hp (incompatibility) vi nm..........................166 2. Phn tch b bn v lp bn vi nm......................................167
3. Phn tch di truyn trong chu trnh cn hu tnh (ti t hp trong nguyn phn)..................................................................................... 171 3.1. S n bi ho (Haploidisation).................................................172 3.2. Ti t hp trong nguyn phn (Mitotic recombination)............. 172 III. Nm men nh l E. coli ca cc t bo eukaryote.......................173 1. Cc nhim sc th nm men nhn to (YAC)................................173 2. Nhng hiu bit mi v t chc ca cc nhim sc th ca nm men 175................................................................................................... 3. Nhng hiu bit mi v ti bn v phin m ca b gen nm men..... 176 4. Nhng hiu bit mi v ADN ty th ca nm men........................ 177 Cu hi v Bi tp..............................................................................178 Ti liu Tham kho............................................................................179 Chng 10. Di truyn T bo cht ....................................................180 I. S di truyn t bo cht.................................................................. 180 1. S di truyn ca cc gene lp th.................................................180 2. S di truyn ca cc gene ty th.................................................... 183 2.1. c im di truyn ca cc gene ty th...................................... 183 2.2. Hin tng bt dc bo cht c................................................ 186 3. Hiu qu ca dng m ln chiu xon v c................................. 188 II. Lp bn lp th v ty th....................................................... 190 1. Lp bn gene ca DNA lp th.................................................190 2. Lp bn gene ca DNA ty th...................................................192 III. Di truyn hc phn t cc bo quan ............................................193
1. Cc b gene lp th (cpDNA)........................................................193 2. Cc b gene ty th (mtDNA)..........................................................195 Cu hi v Bi tp..............................................................................195 Ti liu Tham kho............................................................................195 Chng 11. S iu ha biu hin ca gene..................................... 197 I. Cc nguyn l iu ha v mc kim sot phin m................ 197 II. iu ha hot ng gene prokaryote......................................... 199 1. Cu trc ca operon......................................................................200 2. iu ha dng tnh operon lactose............................................. 202 3. iu ha m tnh operon tryptophan............................................ 204 4. Phin m d (Attenuation)............................................................ 205 III. iu ha biu hin gene eukaryote.......................................... 208 1. S bin i DNA............................................................................209 2. Cc promoter................................................................................ 209 3. Nhng trnh t tng cng phin m (Enhancer).........................210 4. Trnh t bt hot gene (gene silencing)........................................ 211 5. Promoter chn lc (alternative promoter).................................... 211 6. Splicing chn lc........................................................................... 212 Cu hi v Bi tp............................................................................. 213 Ti liu tham kho............................................................................. 213 Chng 12. t bin gene, ti t hp v cc yu t di truyn di ng 215
I. t bin gene..................................................................................215 1. Cc kiu t bin gene.................................................................. 215 1.1. t bin thay th cp base.......................................................... 216 1.2. t bin thm hoc bt base ......................................................217 2. C ch gy t bin im.............................................................. 221 II. Sa cha v bo v DNA.............................................................. 225 1. C ch sa sai sinh hc................................................................. 225 1.1. Quang phc hot (photoreactivation) .........................................225 1.2. Sa sai bng lm mt nhm alkyl (dealkylation)........................226 III. Cc yu t di truyn vn ng (Transposable genetic elements).230 1. Cc yu t di truyn vn ng prokaryote................................. 230 1.1. Gene nhy ca prokaryote.......................................................... 231 1.2. C ch ca s chuyn v............................................................. 232 2. Cc yu t di truyn vn ng eukaryote................................... 233 2.1. Cc retrotransposon.................................................................... 233 2.2. DNA transposon..........................................................................235 Cu hi v Bi tp..............................................................................237 Ti liu Tham kho............................................................................ 238 Chng 13. t bin nhim sc th...................................................239 I. t bin cu truc nhim sc th......................................................239 1. Bin i cu trc trn mt NST:....................................................240
1.1. S pht sinh cc t bin cu trc trn NST...............................240 1.2. Mt on..................................................................................... 240 1.3. Lp on (tng on - Duplication)............................................ 242 1.4. o on (Inversion).................................................................. 242 1.5. Chuyn on (Translocation)......................................................246 II. t bin s lng NST................................................................. 248 1. a bi nguyn................................................................................248 2. a bi th lai................................................................................. 250 3. a bi lch hay a nhim.............................................................. 251 III. t bin gy to hay cm ng..................................................... 255 1. Tc ng gy t bin ca bc x ion ha....................................255 1.1. Bc x ion ha............................................................................ 255 1.2. nh hng ca liu lng (dose) v cng bc x (radiation intensity)............................................................................................ 255 2. Tc ng ca tia t ngoi..............................................................255 3. Cc tc nhn gy t bin ha cht.............................................. 256 Cu hi v Bi tp............................................................................. 256 Ti liu tham kho............................................................................. 257

Bi ging in t Mn: Di truyn hc (45 tit)
Trng Th Bch Phng Khoa Sinh hc, Trng i hc Khoa hc, i hc Hu Chng 1
Bn cht ca vt cht di truyn

Mc tiu ca chng
Gii thiu bn cht ca vt cht di truyn l DNA, thnh phn, cu trc ca phn t DNA, dng DNA khc nhau trong t bo.
S tit: 6 Ni dung I. DNA l vt cht di truyn

Nm 1968, Frederich Miescher (Thy in) pht hin ra trong nhn t bo bch cu mt cht khng phi l protein v gi l nuclein. V sau thy cht ny c tnh acid nn gi l acid nucleic. Acid nucleic c 2 loi l desoxyribonucleic (DNA) v ribonucleic (RNA). Nm 1914, R. Feulgen (nh ha hc ngi c) tm ra phng php nhum mu c hiu i vi DNA. Sau cc nghin cu cho thy DNA ca nhn gii hn trong NST. Nhiu s kin cho gin tip cho thy DNA l cht di truyn. Mi n nm 1944 vai tr mang thng tin di truyn ca DNA mi c chng minh v n nm 1952 mi c cng nhn. 1. Cc chng minh gin tip Nhiu s liu cho thy c mi quan h gia DNA v cht di truyn - DNA c trong t bo ca tt c cc vi sinh vt, thc vt, ng vt ch gii hn trong nhn v l thnh phn ch yu ca nhim sc th. l mt cu trc mang nhiu gen xp theo ng thng.
Tai lieu chia se tai: wWw.SinhHoc.edu.vn u - Tt c cc t bo dinh dng ca bt k mt loi sinh vt no

cha mt lng DNA rt n nh, khng ph thuc vo s phn ha chc nng hoc trng thi trao i cht. Ngc li, s lng RNA li bin i ty theo trng thi sinh l ca t bo. - S lng DNA tng theo s lng bi th ca t bo. t bo sinh dc n bi (n) s lng DNA l 1, th t bo dinh dng lng bi (2n) c s lng DNA gp i. - Tia t ngoi (UV) c hiu qu gy t bin cao nht bc sng 260nm. y chnh l bc sng DNA hp thu tia t ngoi nhiu nht. Tuy nhin trong cc s liu trn, thnh phn cu to ca NST ngoi DNA cn c cc protein. Do cn c cc chng minh trc tip mi khng nh vai tr vt cht di truyn ca DNA. 2. Th nghim bin np DNA (Transformation) Hin tng bin np do Griffith pht hin vo nm 1928 vi khun Diplococcus pneumoniae (gy sng phi ng vt c v). Vi khun ny c hai dng: - Dng S (gy bnh): c v bao t bo bng polysaccharid, ngn cn bch cu ph v t bo. Dng ny to khun lc lng trn mi trng agar. - Dng R (khng gy bnh) khng c v bao t bo bng polysaccharid, to khun lc nhn. Th nghim c tin hnh nh sau: a. Tim vi khun dng S sng gy bnh cho chut, sau mt thi gian nhim bnh, chut cht b. Tim vi khun dng R sng khng gy bnh cho chut, chut sng c. Tim vi khun dng S b un cht cho chut, chut cht d. Tim hn hp vi khun dng S b un cht trn vi vi khun R sng cho chut, chut cht. Trong xc chut cht c vi khun S v R.
Hnh 1.1 Th nghim bin np chut
Hin tng trn cho thy vi khun S khng th t sng li c sau khi b un cht, nhng cc t bo cht ny truyn tnh gy bnh cho t bo R. Hin tng ny gi l bin np. n 1944, ba nh khoa hc T. Avery, Mc Leod, Mc Carty tin hnh th nghim xc nh r tc nhn gy bin np. Nu t bo S b x l bi protease hoc RNAase. th hot tnh bin np vn cn, cng t RNA v protein khng phi l tc nhn gy bnh. Nhng nu t bo cht S b x l bng DNAase th hot tnh bin np khng cn na, chng t DNA l nhn t bin np. Kt qu th nghim c tm tc nh sau: DNA ca S + t bo R sng chut cht (c S, R )
Tai lun: hin tng bin np l mt chng minh sinh ha xc nhn lieu chia se tai: wWw.SinhHoc.edu.vn Kt
rng DNA mang tn hiu di truyn. Nhng vai tr ca DNA vn cha c cng nhn v cho rng trong cc th nghim vn cn mt t protein.
Hnh 1.2 Vt cht di truyn ca phage l DNA
3. S xm nhp ca DNA virus vo vi khun Nm 1952, A. Hershey v M. Chase tin hnh th nghim vi bacteriophage T2 xm nhp vi khun E.coli. Phage T2 cu to gm v protein bn ngoi v rut DNA bn trong. Th nghim ny nhm xc nh xem phage nhim vi khun bm cht no vo t bo vi khun: ch DNA, ch protein hay c hai. V DNA cha nhiu phosphor, khng c lu hunh; cn protein cha lu hunh nhng khng cha phosphor nn c th phn bit gia DNA v protein nh ng v phng x. Phage c nui trn vi khun mc trn mi trng cha cc ng v phng x P32 v S35. S35 xm nhp vo protein v P32 xm nhp vo DNA ca phage
Tai nghim: phagese tai: wWw.SinhHoc.edu.vn nhim lieu chia T nhim phng x c tch ra v em Th
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vo cc vi khun khng nhim phng x, chng s gn ln mt ngoi ca t bo vi khun. Cho phage nhim trong mt khong thi gian bm vo vch t bo vi khun v bm cht no vo t bo vi khun. Dung dch c lc mnh v ly tm tch ri t bo vi khun khi phn phage bm bn ngoi vch t bo. Phn tch phn trong t bo vi khun thy cha nhiu P32 (70%) v rt t S35, phn bn ngoi t bo vi khun cha nhiu S35 v rt t P32. Th h mi ca phage cha khong 30% P32 ban u Th nghim ny c chng minh trc tip rng DNA ca phage T2 xm nhp vo t bo vi khun v sinh sn to ra th h phage mi mang tnh di truyn c kh nng n nhim vo cc vi khun khc.
Hinh 1.3 S xm nhp DNA cua virus vao vi khun
II. Thnh phn v cu to ha hc ca acid nucleic

DNA v RNA l nhng hp cht cao phn t. Cc n phn l cc nucleotide. Mi nucleotide gm ba thnh phn - H3PO4
Tai lieu chia se tai: wWw.SinhHoc.edu.vn - ng desoxyribose (DNA ), ribose ( RNA)

- Nitrogenous base DNA + Purin + Pyrimidin (a) Adenin (A) Guanin (G) Cytosin (C) Timin (T) RNA Adenin (A) Guanin (G) Cytosin (C) Uracin (U)
(b)
(c)
Hnh 1.4 Thnh phn ng v base ca nucleotide (a) Base purin va pyrimidin (b) ng ribose va deoxyribose (c) S khac nhau gia Thymine va Uracil
Trong nucleotide, base purin s gn vi C1 ca ng N9. Nu l pyrimidin th s gn vi C1 ca ng N3. C5 ca ng gn vi nhm phosphate.
Tai lieu chia se tai:ni vi nhau nh mi lin kt gia nhm wWw.SinhHoc.edu.vn Trong mch, 2 nucleotide
3-OH ca ng vi nhm -OH ca H3PO4, cng nhau mt i mt phn t nc. Nu phn t ch gm ng v nitrogenous base gi l nucleoside. 1. DNA 1.1. Cu to ha hc ca DNA
Hnh 1.5 S bt cp b sung ca cc base ca hai mch n
Trn c s cc nghin cu ca mnh, Chargaff (1951) a ra kt lun: + S lng A = T, G = C
Tai lieu chia +T tai: trng cho mi loi sinh vt. se c wWw.SinhHoc.edu.vn + T s A
G+X Cc base cn bn ca acid nucleic bt cp b sung Cng trong thi gian ny, Wilkins v Franklin (ngi Anh) nghin cu, phn tch tn x bng tia rnghen, kt lun: + Cc purin v pyrimidin c cu trc phng, mt phng ca chng c xp vung gc vi trc di ca mch polynucleotide ci ny xp chng ln ci kia, khong cch trung tm gia hai mt phng k nhau l 3,4Ao + Mch polynucleotide xon thnh l xo quanh trc gia, mi bc xon l 34Ao (ng vi 10 nu) + Vic so snh nng DNA o c vi cc s liu tnh ton trn c s sp khng gian ca cc nguyn t cho thy DNA c nhiu hn mt mch polynucleotide. Nm 1951, J. Watson v F. Crick: tng hp cc s liu phn tch ha hc v tn x ca tia X, xy dng nn m hnh cu trc phn t DNA. Theo m hnh ny, phn t DNA c nhng c trng ch yu trong cu trc khng gian nh sau:
Hnh 1.6. Mi lin kt hydro gia A-T v G-C
Tai lieu chia se tai: wWw.SinhHoc.edu.vn 1. Phn t DNA gm hai chui polynucleotide xon song
ngc chiu quanh mt trc chung.
song
2. Cc gc base quay vo pha trong ca vng xon, cn cc gc H3PO4, pentose quay ra ngoi to phn mt ca hnh tr. Cc mt phng ca phn t ng nm v pha phi ca cc base. Cn cc base th xp trn nhng mt phng song song vi nhau v thng gc vi trc phn t. Khong cch gia cc cp base l 3,4 Ao. Chng lch nhau mt gc 360 nn c 10 gc (10 nucleotide) to nn mt vng quay.
Hnh 1.7 Chui xon kp DNA
3. Chiu cao ca mi vng xon l 34 Ao, gm 10 bc thang do 10 cp base to nn. ng knh ca vng xon l 20 Ao.
Tai lieu chia se tai: wWw.SinhHoc.edu.vn c 4. Hai chui polynucleotide gn vi nhau qua lin kt hydro
hnh thnh gia cc cp base ng i din nhau theo nguyn tc b sung cp i nghim ngt: A lun lun lin kt vi T bng 2 mi lin kt hydro, G lin kt vi X bng 3 mi lin kt hydro. Do trong phn t DNA tng s base loi pirimidin lun bng tng s cc base loi purin (quy lut Chargaff). + Khong cch gia hai mch polynucleotide lun xc nh, khng thay i. Khong cch ny bng kch thc ca mt base loi purin cng vi kch thc ca mt base loi pirimidin. + A lun lun i vi T l v gia 2 base ny ch c kh nng hnh thnh nn hai lin kt hydrro cc v tr N6 - O6 v N1 - N1. G lun lun i vi X v gia 2 base ny c th to ra 3 lin kt hydro cc v tr N6 - O6, N1 -N1 v N2 - O2. V vy m A ch lin kt vi T v G ch lin kt vi C. 5. Tnh cht b sung gia cc cp base dn n tnh cht b sung gia hai chui polynucleotide ca DNA. Do bit thnh phn, trt t sp xp ca cc nucleotide trn chui ny s suy ra thnh phn, trt t sp xp ca cc nucleotide trn chui kia. c im quan trng nht ca m hnh l i song song (antiparallel). cc baz tng ng i din nhau, hai mch cn phi b tr: u ca si ny i din vi ui ca si kia. M hnh Watson-Crick ra i t nm 1953 v trong vng 25 nm tip theo n c cng nhn v s dng rng ri. Mi n nhng nm 70, nh dng cc phn tch chnh xc nhiu dng DNA c pht hin, dng thng gp l dng B theo m hnh ca Watson-Crick, y l cu trc ph bin cho hu ht sinh vt. Mi dng DNA l mt dng h cc phn t c kch thc dao ng quanh cc tr s trung bnh Hai ch s c dng nh gi DNA - Ch s h: l chiu cao gia hai nu k nhau. - Ch s n: s nucleotide ca mt vng xon Ngoi DNA dng B, cn nhiu dng xon phi khc (A, C, D ...) chng phn bit vi DNA dng B v khong cch gia cc base cng nh nghing ca chng so vi trc v s phn b trn chui kp.
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Tai lieungi tase tai: wWw.SinhHoc.edu.vn khung chia cn pht hin ra mt dng DNA c b Gn y,
zigzag v ng xon theo chiu tri, gi l DNA xon tri hay DNA Z, trn mi vng xon c ti 12 cp base. Gii thch s tn ti ca DNA Z c nhiu quan nim khc nhau: Theo Watson, ch trong nhng iu kin c bit, nh nng mui cao th cc vng cha trnh t ...GCGCGC... chuyn sang cu hnh Z, ngc li nng mui thp chng quay tr li dng B. iu chng t DNA Z c th ng vai tr gim sc cng cc b trong phn t DNA siu xon hoc c th tng tc c th vi cc protein iu ha. Tuy nhin A. Rich cho rng DNA Z xy ra trong t nhin m bng chng l c mt trong rui gim bnh thng. C th l vng DNA Z nm xen k vi vng DNA B v chng c th xoay hnh dng thnh dng B khi xy ra cc bin i ha hc no lm cho DNA Z tr nn khng n nh. Rich cn gi rng nhng gen nm cc vng b xoay nh th th c th tho xon sau v bt u phin m. Nh vy m protein c th c tng hp. Mc d y mi ch l gi thit song khm ph ny cung cp mt cng c tim nng cho nghin cu v hot ng ca cc gen v DNA.Vic pht hin cc dng DNA cho thy DNA trong t bo khng n iu. ty trng thi sinh l m DNA dng ny hoc dng khc.
Hnh 1.8 DNA dng xon kp Z a. M hnh dng B ca Watson-Crick, l dng xon phi vi trc u b. M hnh dng Z, l dng xon tri vi trc khng u
1.2. DNA cun li trong t bo Hu ht trong c th sinh vt, DNA c chiu di di hn rt nhiu ln so vi chiu di ca t bo.
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V d: phage T2 c chiu di t bo khong 0,16 m, trong khi chiu di ADN ca chng khong 50 m.
Hnh 1.9 Cc dng thng, vng trn v xiu xon ca DNA
Do DNA trong t bo phi cun xon. S cun xon ny rt tinh vi v trong qu trnh tn ti, cc gen phi hot ng, nh vy n phi l mt cht c hot tnh thng xuyn Ngi ta thy DNA c th 3 dng cu trc: - Dng siu xon: mch kp vn xon li thnh hnh s 8. y l dang t nhin vi khun.
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Tai lieu chia si DNA wWw.SinhHoc.edu.vn b se tai: cng trn c c do DNA siu xon - Dng vng trn:
ct t 1 trong hai mch kp. - Dng thng: khi DNA b ct t c hai mch. M hnh v b gen ca E .coli E. coli, chiu di DNA c rt ngn ng k, s cun li c thc hin nh vo cc RNA ni. Khi cc RNA ni b ct th cc DNA bung di ra, thun li cho s sao chp DNA. Nu mch DNA b ct, DNA c tho xon, cng ra thun li cho s tng hp protein.
Hnh 1.10 M hnh cu trc nhim sc th (b gen) ca E. coli (Theo Pettijohn v Hecht, 1974)
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Hnh 1.11 S tho xon DNA trong t bo vi khun
2. RNA cc sinh vt nh: thc khun th, virus ca ng vt, virus ca thc vt... th vt liu di truyn l RNA. cc sinh vt bc cao c RNA l bn sao m ca DNA. RNA c cu to t cc n phn l cc ribonucleotide. Ging vi nucleotide, mi ribonucleotide gm ba thnh phn: ng ribose, H3PO4, baznitric (T c thay bng U). Trong t bo c ba loi RNA: 2.1. RNA riboxom (ribosomal RNA-rRNA) rRNA cng vi protein cu to nn ribosome. rRNA chim t l cao trong t bo c th n 75% ca tng RNA. cc ribosome khc nhau c cc rRNA khc nhau, chng c c trng bi hng s lng S: - Eukaryote : ribosome c h s lng khi ly tm l 80S, gm hai n v: + n v ln ( 60S) c rRNA 28S; 5,8S; 5S + n v nh (40S) c rRNA 18S - Prokaryote v lc lp, ty th c h s lng khi ly tm l 70S, gm 2 n v: + n v ln (50S): c loi rRNA 23S; 5S + n v nh (30S): c rRNA 16S
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Tai lieu chia cu tai: bc I (mch thng) v cu trc bc hai. se trc wWw.SinhHoc.edu.vn RNA ribosom c
Trong ribosome, cc rRNA tn ti dng cu trc bc hai. RNA ribosom c cu to l mt si xon c nhiu vng lin kt i theo nguyn tc b sung A lin kt vi U, G lin kt vi X v c khi G lin kt vi U. Trong t bo rRNA chim t l cao c th ln n 75-80% tng s RNA
Hnh 1.12 rRNA cu to nn ribosom
2.2. RNA vn chuyn (Transfer RNA - tRNA) Mi tRNA gn vi mt phn t amino acid, mang n ribosome tham gia tng hp protein. Mi tRNA c hiu cho mt loi amino acid. C hn 20 loi tRNA khc nhau tng ng vi hn 20 loi amino acid. Trong thc t, ngi ta thy s lng tRNA ln hn rt nhiu so vi s lng amino acid v mt amino acid c nhiu b ba m ha. ng thi cng mt b ba m ha, vn c th c nhiu tRNA do hin tng bin i ca cc nucleotide trong tRNA to nn cc loi tRNA mi v trong qu trnh tng hp tRNA, sau khi hnh thnh chui polynucleotide cn chu s tc ng ca cc yu t ca mi trng ni v ngoi bo lm cc nucleotide b bin i, to ra cc tRNA mi. Cc tRNA cng tham gia vn chuyn mt acid amin l cc izoaceptor. S lng izoaceptor thay i ty acid amin.
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Tai trc bc I case tai:tRNA vn chuyn c phn t lng nh: lieu chia tRNA: wWw.SinhHoc.edu.vn Cu
25.000-30.000, gm 75-90 nucleotide, c hng s lng 4S. Trong thnh phn cu trc ca tRNA c khong 10% cc nucleotide him vi khong 30 loi khc nhau. Mi cu trc ca tRNA u c 2 u 5' v 3' ging nhau: u 5' lun cha G vi gc P t do, cn u 3' lun c 3 nucleotide l CCA 3'-OH. Nhm 3'-OH ca A c th lin kt vi acid amin to phc hp tRNA-aminoacyl. Chui polynucleotide cun li c nhng on to mch xon kp, hnh thnh cu trc bc hai ca tRNA.
Hnh 1.13 Cu trc ca tRNA
Enzyme aminoacyl tRNA synthetase gn amino acid vi tRNA tng ng. Mi enzyme c hiu cho mt loi amino acid ring bit v xc tc phn ng gn vi tRNA ca n nh nng lng ATP to ra aminoacyl tRNA. Phc hp aminoacyl tRNA n ribosome gn vi mRNA bng nh cc b ba i m (anticodon) trn tRNA bt cp b sung vi cc b ba m ha (codon) trn mRNA.
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Tai tRNA c mt se c tnh cu trc chung: chiu di khong 73lieu chia s tai: wWw.SinhHoc.edu.vn Cc
93 nucleotide, cu trc gm mt mach cun li nh hnh l ch ba nh bt cp bn trong phn t. u mt 3 c trnh t kt thc l CCA, amino acid lun gn vo u ny. u 5 cha gc phosphate ca G. Mi tRNA c c 4-5 vng vi chc nng khc nhau: - Vng DHU: c cha nucleotide dihydrouridin, vng ny c chc nng nhn bit aminoacyl tRNA synthetase - Vng anticodon: c m trn mRNA theo nguyn tc kt cp anticodon codon. - Vng ph: c th khng c mt s RNA. - Vng TC: c cha nucleotide pseudouridin, vng ny c chc nng nhn bit ribosom vo ng v tr tip nhn aminoacyl tRNA (v tr A) - u 3 CCA: v tr gn vi acid amin. tRNA chim khong 15% tng s RNA ca t bo 2.3. RNA thng tin (messenger RNA mRNA) RNA thng tin lm nhim v truyn t thng tin di truyn t DNA n protein. mRNA chim khong 5% tng s RNA t bo. Cu trc ca mRNA: 5 m GxpYp vng 5 khng m ha X, Y c th l A hoc G DNA polymerase khi s phin m on nm ngay trc vng m ha c gi l on 5 khng m ha (5-non coding). Do mRNA c on u mang cc tn hiu cho ribosome nhn bit gn vo dch m. ui 3 sau du kt thc c on 3 khng m ha l ni gn poly-A. Cc mRNA ca prokaryote c na thi gian (half life) tn ti ngn trung bnh 2 pht. Cc mRNA ca Eukaryote c na thi gian tn ti khong 30 pht - 24 gi.
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AUG vng m ha
UAG vng 3
khng m ha
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V tr gan Rb
Tai lieu chiatrse Rb wWw.SinhHoc.edu.vn tai: V tr gan Rb V gan

Ma khi au AUG Ma khi au AUG Ma khi au AUG
5 3
Vung khong ma hoa
UAA ma ket thuc
UAA ma ket thuc
UAA ma ket thuc
P1
P2
P3
Hnh 1.14 mRNA Prokaryote

Vung khong ma hoa 5 G Ma ket thuc UAA A-A-A--3 AUG 5 CAP V tr gan Rb Vung khong ma hoa
P P P
Hnh 1.15 mRNA eukaryote
2.4. Ribozym v self- splicing Vo 1981, pht minh v vai tr xc tc ca mt s phn t RNA lm o ln quan im v cht ny. Cc phn t rRNA ca cc loi nguyn sinh ng vt, lc u c tng hp vi mt s lng ln tin cht, t s cc rRNA ny s c mt c to ra bng cch t ct ni (self - splicing). Qu trnh ct ni ny c th xy ra in vitro trong s vng mt ca protein. iu cho thy rng cc trnh t intron t n c hot tnh xc tc tng t enzyme. Phn ng self-splicing trong trnh t intron t xc tc qu trnh t ct ri khi phn t rRNA loi Tetrahymena qua 2 bc: + phn ng c bt u khi nucleotide G gn vo trnh t intron, ng thi ct mch RNA.
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Tai lieuca RNA mi va c to ra gn vo u bn kia ca chia se tai: wWw.SinhHoc.edu.vn + u 3
intron hon thnh phn ng ni lin
Hnh 1.16 Hot ng ct intron v ni exon trn mRNA
Trnh t intron di 400 nucleotide c tng hp trong ng nghim v n cun li to phc hp b mt c hot tnh tng t enzyme trong cc phn ng vi cc RNA khc. Mc d splicing phn ln khng c thc hin t ng nh Tetrahymena nhng hin tng ny cng c pht hin nhng sinh vt khc, c nm v vi khun. Cc RNA c kh nng t xc tc c gi l ribozyme. Pht hin ny c ngha quan trng trong vic tm hiu c ch v ngun gc s sng.
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Hnh 1.17 Phn ng self-splicing ca RNA
III Cc tnh cht ca DNA

1. Bin tnh (denaturation) v hi tnh (renaturation) Hai mch n ca phn t AND gn vi nhau nh cc lin kt hydro.Khi un nng DNA t t, vt qu nhit sinh l (khong 8095oC), cc lin kt hydro gia 2 mch b t v chng tch ri nhau. Trc tin cc mi lin kt A-T, khi nhit > 90 oC cc lin kt G -C b t. l hin tng bin tnh ca DNA. Nhit m 2 mch DNA tch ri nhau c gi l im chy melting poin) ca DNA: Tm. Nhit ny c trng cho mi loi DNA, ph
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thuc vo s lng cc lin kt hydro. DNA c t l G-C cao s c im chy cao. DNA c 60% G-C th im chy l 95oC.
Hnh 1.18 S bin tnh v hi tnh ca DNA
Ngoi nhit , ngi ta cn dng cht formanide (NH 2 -CH = 0) lm bin cht DNA 40oC Cc DNA b bin cht c h nhit t t, 60o -700C cc nucleotide s gn li vi nhau to nn DNA mch kp. Hin tng ny gi l hi tnh.
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Taith bit chia DNA b bin tnh hoc cha nh vo s gia tng lieu c se tai: wWw.SinhHoc.edu.vn C
hp th tia cc tm khi b bin tnh v s gim hp thu tia cc tm khi hi tnh. Gi tr mt quang tng ln khi phn t mch i chuyn thnh mch n, iu ny xy ra do hiu ng siu sc (hyperchromic effect), hoc da vo s thay i lng t trong ng nghim khi ly tm. 2. Lai acid nucleic S dng c tnh bin tnh ri hi tnh c th tin hnh lai DNA vi DNA, DNA vi RNA, RNA vi RNA. Nguyn tc: ly DNA A lm bin tnh thnh mch n, trn vi DNA B cng b bin tnh thnh mch n. Dung dch c h nhit t t xy ra hi tnh. y l kiu lai lng hay lai trong dung dch. Qu trnh hi tnh xy ra, si A kt vi A, B kt vi B, ng thi c si A kt vi B to thnh phn t lai. Mun lai c vi nhau, gia 2 loi DNA phi c nhng on c trnh t b sung nhau. C th dng ng v phng x nh du pht hin on lai. Hin nay cn s dng phng php lai trn pha rn, c s dng rng nht: + Phng php Southern blot, dng cho DNA + Phng php Northern blot dng cho RNA + Phng php dot (im) v slot (khe) blot dng cho RNA v DNA - Lai ti ch (in situ hybridization) l kiu lai phn t trong trnh t acid nucleic cn tm (trnh t ch) nm ngay trong t bo hay trong m. Lai tai ch cho php nghin cu NST, khun lc hay m t bo m khng cn tch chit chng. Dng phng php lai DNA: + C th xc nh mi quan h h hng gia cc loi. DNA ngi v DNA chut ch lai c 25%. + C th tin hnh lai mRNA vi DNA xc nh v tr gen trn DNA to ra mRNA tng ng. Phng php lai acid nucleic gip hiu chi tit hn v b gen, n l c s ca phng php chn on mi dng acid nucleic ang uc s dng rng ri.
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Hnh 1.19 Pht hin cc DNA lai vi mu d
IV. Nhng cu trc cha DNA trong t bo

1. Nhng on DNA cha thng tin di truyn i phn t DNA l do polynucleotide to thnh, c chia lm nhiu on. Mi on l mt n v chc nng, gi l gen Gen c nh ngha trong di truyn hc: + Mendel l ngi u tin nu ln khi nim nhn t di truyn + J. Morgan c th ha khi nim v gen: gen nm trn nhim sc th chim mt locus nht nh. Gen l n v chc nng xc nh mt tnh trng. + Sau khi hc thuyt trung tm ra i: gen l on DNA trn nhim sc th khng nhng m ha cho cc loi protein m c cc loi RNA. + Cui nhng nm 70, sau khi pht hin ra gen gin on: gen l mt on DNA m bo cho vic to ra mt polypeptid n bao gm c vng trc v sau vng m ha cho protein v c nhng on khng m ha xen gia cc on m ha. Hin nay c th nh nghi tng qut nh sau: gen l n v chc nng c s ca b my di truyn chim mt locus nht nh trn NST v xc nh mt tnh trng nht nh. Cc gen l nhng on vt cht di truyn m ha cho nhng sn phm ring l nh cc RNA c s dng trc tip cho
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tng hp cc enzym, cc protein cu trc hay cc mch polypeptid gn li to ra cc protein c hot tnh sinh hc. Ton b nhng gen khc nhau ca c th, gi l Idiotype. Eukaryote n bao gm cc gen trn nhim sc th (chromotype) v cc gen ngoi nhn (plasmotype). prokaryote, n bao gm b gen v plasmid. 2. Virus cha DNA v virus cha RNA Virus gy bnh m thuc l (mosaic tobacco virus - MTV) l virus cha RNA si n. N l mt ht hnh que di 300 nm, c ng knh 18 nm. Bn ngoi c mt v cha 2130 phn t v mt vng xon RNA bn trong. Chiu cao vng xon: 23Ao, khi lng phn t = 2.106 vC.
Hnh 1.20 Virus khm thuc l a. nh virus khm thuc l chp bng knh hin vi in t phng i 37.428X b. RNA iu khin s hnh thnh tnh trng v ca virus
Mt s virus cha DNA si i nh cc thc khun th T2, T4, T6 cha DNA mch i thng, di. C cha 2.105 i nucleotide, khi lng
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phn t: 130.10 vC. Khi lc thm thu ca mi trng thay i t ngt, phn t DNA ny thot ra khi v protein, ngi ta chp nh c nh DNA ca tjc khun th T2 vi chiu di 0,05 mm (50m), phn t ny xp gn phn u ca thc khun th. Tt c thc khun th T s chn cha DNA vi mch polynucleotide ging nhau, nn khi trn ln cc DNA mch n b bin tnh ca chng vi nhau th cc mch n ny c th to thnh phn t lai. Phn t DNA ca T3, T7 khng th hnh thnh phn t DNA lai vi DNA ca T s chn. Cn virus X174 c cha DNA si n gm 5400 nucleotide vi khong 9 gen. 3. Nhim sc th chnh v plasmid ca vi khun DNA ca vi khun lm thnh th nhn, tip xc trc tip vi t bo cht, khng c mng nhn lm gii hn. DNA ca th nhn l DNA mch vng, xon kp V d: DNA E.coli c ng knh 350 m, gm 4.106 i nucleotide v cha khong 500 gen xp ni tip nhau thnh chui di chi phi tt c cc hot ng chc nng ca s sng. Plasmid cng l phn t DNA mch kp, dng vng bn cnh th nhn. Khi lng phn t trung bnh khong 1% DNA ca th nhn. Cc plasmid c th gn tm thi hoc vnh vin trn NST chnh ca vi khun. C th tham gia s t nhn i v tham gia tip hp khc nh l mt phn ca NST chnh. 4. Nhim sc th Eukaryota. 4.1 Cc trnh t lp li v n c DNA c ct thnh tng on nh, cho bin tnh, sau hi tinh th cc on c trnh t b sung d ti t hp vi nhau hn cc on khc. Nh vy c th nhn bit c cc trnh t lp li. Da vo phn DNA thnh ba loi: + DNA n c (ti hp rt chm) + DNA lp li trung bnh (ti hp nhanh va) + DNA lp li cao (ti hp rt nhanh)
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Tai lieu chia sethng tin m ha cho cc protein nhng trong tai: wWw.SinhHoc.edu.vn Mc d DNA mang
thc t ch c khong 10% trong s 3 t cp nucleotide trong genome ca ngi thc s lm chc nng ny. Cn c vo c im cu trc v phn, chia DNA thnh cc loi sau: - DNA n c (Single copy DNA) y l loi ph bin nht, chim khong 75% genome. Cc on DNA ny ch thy 1 ln (hoc vi ln) trong genome. Mt phn nh ca DNA loi ny l cc gen m ha cho protein. Hu ht cc DNA n c l cc intron hoc l cc on nm xen gia cc gen. - DNA lp li (repetitive DNA) Chim 25% cn li ca genome, y l cc on DNA c lp i lp li hng ngn ln trong genome. DNA lp li gm 2 loi: + DNA v tinh (satellite DNA): loi DNA tp trung 1 s vng nht nh trn NST, chng xp ui nhau, ci ny tip ci kia. Loi ny chim 10% b gen. + DNA lp li ri rc: loi DNA ny chim khong 15% genome, gm 2 loi: Cc yu t ri rc c kch thc ngn SINEs (short interspersed repetitive elements): kch thc t 90-500 bp. Trong nhm ny c loi DNA lp li tn Alu vi kch thc khong 300 bp, mang on DNA c th b enzyme hn ch Alu I ct (y l enzyme c ngun gc t vi khun Arthrobacter luteus). on lp Alu l 1 h bao gm cc on DNA c ging nhau cao, phn b ri rc khp h gen vi khong 300.000 bn sao, chim khong 2-3% ton b DNA ca ngi, chng c xem nh l cc yu t vn ng. 2 u mi on Alu c cc on lp cng chiu ngn khong 7-10 bp. Bn trong on Alu c cc on lp di khong 40 bp. im c bit ca cc on lp DNA ny l c th to ra bn sao ca mnh v c th ci vo cc phn khc ca b gen. Hin tng ny i khi c th lm gin on mt gen m ha cho protein no v gy ra tnh trng bnh l di truyn. Vai tr ca cc trnh t Alu n nay cha r. Mt iu ng kinh ngc l c s tng ng (homologus) t 80-100% gia phn 3' ca Alu vi u mt 5' v 3' ca RNA 7SL, l phn tng tc vi cc tn hiu peptid trc khi vn chuyn ra t bo cht. Vic xc nh trnh t nucleotide ca
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Alu cho thy c t nht 6 nhm ph v tt c u bt ngun t DNA m ha cho RNA 7SL. Cc yu t ri rc c kch thc di LINEs (long interspersed repetitive elements): bao gm cc h LINE 1 (hay Kpn 1) v THE 1. Cc trnh t LINE c chiu di khong 6000-7000 bp vi gn 5.000 bn sao nguyn vn v 100.000 bn sao tng phn ri rc khp b gen ngi. Chng l nhng trnh t lp li khng m ha di nht v thng vng giu AT. Cc bn phin m trnh t LINE gn vi protein to thnh phc hp ribonucleoprotein. mt dng t bo ngi b ung th (teratocarcinome), ngi ta quan st thy c cc ribonucleoprotein ny. S xen on LINE vo cc v tr khc nhau c th gy hu qu nht nh, nh trong mt trng hp bnh mu khng ng A (hemophilia). 4.2. Nhim sc th ca Eukaryota Nhim sc th cha mt phn t DNA thng, mch kp. NST Eukaryote gm DNA v protein, trong s histon l protein ct li trong vic cun li v iu ha hot tnh ca DNA. S hnh thnh NST k gia t chui xon kp DNA qua h thng cc bc cu trc sau: + Nucleosome l n v cu trc ca NST c to nn do si DNA di qun quanh cc protein histon thnh si 11nm. n v ny l phc hp gm 146 cp nucleotide ca DNA qun quanh 8 phn t histon: 2H2A, 2H2B, 2H3 ,2H4. Cc nucleosome k nhau c ni qua mt phn t histon trung gian H1. + Si chromatin dy 30nm: cc nucleosome xp st nhau to thnh phc hp nucleoprotein. + Vng xp cun dy 300 nm do si chromatin sau nhiu ln xon un khc to nn. + Cht d nhim sc 700 nm + K gia 1400nm.
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Hnh 1.21 DNA qun quanh bi protein histon
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Hnh 1.22 Phc hp nucleoprotein cun li thnh NST
4.3. Trnh t CEN: trnh t lp li cao CEN l ca cc tm ng. 4.4. Trnh t TEL: thuc cc telomer (u mt ca NST) vi nhiu vai tr khc nhau: bo v u mt NST khi b ct bi nuclease, gi chiu di ca NST khi sao chp, gn vi mng nhn v km hm s biu hin ca cc gen u mt. Cc trnh t TEL c tnh bo tn cao trong tin ha. Chng c s ln lp li cao, giu A v C.
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Cu hi n tp
1. Nu chng minh gin tip cho thy DNA l vt cht di truyn. 2. Trnh by th nghim bin np qua chng minh DNA l vt cht di truyn. 3, Cc c im ca m hnh cu trc ca Watson v Crick (1953). 4. M t cc dng tn ti ca DNA trong t bo. 5. M hnh v cu trc b gene ca E. coli. 6. Cu trc v chc nng cc loi RNA trong t bo Eukaryote. 7. DNA v RNA khc nhau nhng cu phn no 8. Hy nu cc tnh cht ca phn t DNA. 9. Cc trnh t lp li DNA Eukaryote 10. Trnh by cc mc kt cun ca DNA hnh thnh nhim sc th.
Ti liu tham kho

Trnh Vn Bo, Phan Th Hoan, Trn Th Thanh Hng, Trn Th lin, Trn c Phn, Phm c Phng, Nguyn Vn Rc, Nguyn Th Trang. 2002. Cc nguyn l sinh hc. NXB Y hc H Ni. Phm Thnh H (2000). Di truyn hc. NXB Gio Dc. Nguyn B Lc (2004). Acid nucleic v sinh tng hp protein. Trung tm o to T xa, i hc Hu. 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. 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.
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Chng 2
Tai lieu chia se tai: wWw.SinhHoc.edu.vn Sao chp DNA
Mc tiu ca chng
Gii thiu v sao chp DNA, nguyn tc ca sao chp v cc nhn t tham gia vo qu trnh sao chp DNA, cc h thng sa sai DNA nhm duy tr tnh chnh xc ca thng tin di truyn qua cc th h.
S tit: 3 Ni dung I. S bn vng ca DNA vi thi gian v qua nhiu th h

1. DNA b bin i ngay c khng sao chp
Hnh 2.1 S mt amin ca cc base (desamination)
DNA l nhng phn t rt di, nhng mnh (ng knh: 20 A o), li thng xuyn chu tc ng mi trng bn trong v bn ngoi t bo nn d c nhng t gy, bin i ngay c khi khng c sao chp.
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Tai lieutnh ra rng tai: wWw.SinhHoc.edu.vn 5000 chia se DNA ca t bo ngi mi ngy mt Ngi ta
purin do qu trnh mt purin (depurination): di tc dng ca nhit lin kt N-glycosil b thy phn. Qu trnh bin i lm mt amin (desamination): bin cytosin thnh uracin. Mi ngy t bo ngi c khong 100 bin i nh vy. Con ngi cng thng xuyn chu tc ng ca tia t ngoi lm to ra cc dimer thymine.
Hnh 2.2 S hnh thnh dimer thymine di tc dng ca tia t ngoi
2. Trnh t nucleotid c duy tr vi mc chnh xc rt cao qua nhiu th h Dng cc nucleotid v cc enzyme DNA polymerse tng hp DNA in vitro. Sai st trong trng hp ny l 10-5. Nh vy sao chp trong ng nghim c mc chnh xc cao, nhng i chiu ln cc sinh vt th mc sai st ny hy cn qu ln.
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Tai lieu nh gi tntai:cc t bin mi xut hin trong qun th chia se s wWw.SinhHoc.edu.vn Bng cch
ln v theo di bin i enzyme no trong nui cy m t bo, ngi ta tnh c rng trong c th sinh vt sai st trong khi sao chp in vivo l 1.10-9. nh gi tc bin i trong tin ha cng khng nh mc chnh xc rt cao trong sao chp in vitro. 3. Cc h thng bo v DNA Trong t bo c mt lot h thng bo v DNA: - Cc sinh vt tin nhn v nhn thc u cha cc enzyme c nhim v methyl ha nhng im nht nh. Cc enzyme ct hn ch ca mi dng vi khun khng ct DNA ca chng v c methyl ha nhng im cn thit, cn DNA ngoi lai v khng c methyl ha nhng im nht nh nn b ct. T bo cn c cc h thng sa sai (repair system): + Sa sai bng cch ct b ri tng hp si mi Cc enzyme DNA polymerase I, II, III u c hot tnh polymerase ha, cn c hot tnh exonuclease theo hng 5-3.
Hnh 2.3 Sa sai bng ct b v tng hp li on b hng
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Tai lieu chiach ti t hp se tai: wWw.SinhHoc.edu.vn + Sa sai nh c

Ngay c khi khng c sao chp vn c h thng bo v: do DNA c hai mch, khi sai hng trn mt mch, c th da vo mch cn li tng hp on sai hng. Mt s enzyme c hiu pht hin s bt cp sai, nh trong trng hp mt purin. C khong 50 enzyme chuyn pht hin v sa cc sai hng trn phn t DNA.
Hnh 2.4. Sa sai nh enzyme
4. Sa sai do phc quang hi Di tc dng ca tia t ngoi, lm cc timin ng gn nhau s gn li to thnh dimertimin. Khi tr li nh sng, nh sng s kch thch mt enzyme ct b dimerthymin to timin bnh thng. Hin tng nh sng kch thch mt enzyme ct b dimerthymin gi l quang phc hi.
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5. H thng SOS
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, tng cng sa sai. E.coli, h thng ny c lin quan vi 2 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 m nhm cc gen ca h thng SOS. Mt vi sn phm ca DNA b tn thng s lm hot ha protease recA. Protein recA b hot ha s ct b protein lexA, cho php cc gen 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 nhanh hn bnh thng. + Nu sa sai kp, t bo n nh, sinh trng tr li + Nu khng sa sai kp th t bo phi chp nhn hoc cht hoc b t bin
Hnh 2.5 Sa cha do quang phc hi
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II. C ch phn t ca sao chp DNA

1. Nguyn tc chung - DNA sao chp theo khun.
u im: + Vi phn t ln nh vy th vic tng hp theo khun s chnh xc hn + Tit kim c ezyme + t hiu qu nhanh - Sao chp theo nguyn tc bn bo tn (semi-conservative) phn t DNA mi c tng hp gm mt mch c lm khun v mt mch mi tng hp - Qu trnh tng hp DNA xy ra i hi phi c mi (primer) - Qu trnh tng hp xy ra theo chiu 5 - 3.
Hnh 2.6 Sao chp DNA theo nguyn tc bn bo ton
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2. Th nghim tng hp nhn to DNA
Kornberg (1956) thc hin phn ng tng hp DNA in vitro. Trong qu trnh tng hp ng s dng DNA polymerase I, 4 loi desoxynucleotid triphosphate (ATP, GTP, CTP, TTP), Mg2+ lm xc tc. Ngoi ra cn c t DNA lm khun mu. 3. Th nghim chng minh c s t nhn i theo nguyn tc bn bo tn Meselson, Stahl (1958) chng minh kiu sao chp bn bo tn. Nui E.coli nhiu th h trn mi trng c ngun nit ng v nng N 15. Nh vy tt c DNA ca vi khun u mang ng v nng N15 thay cho N14 bnh thng. Sau t bo c chuyn sang mi trng ch cha N14 nh, mu cc t bo c ly ra theo nhng khong thi gian u n v chit tch DNA. Bng phng php ly tm trn thang nng CsCl, cc loi DNA nng, nh v lai c tch ra.
Hnh 2.7 Th nghim ca Meselson v Stahl
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Tai qu cho thy DNA nng ban u (th h 0) cha N , sau mt lieu chia se tai: wWw.SinhHoc.edu.vn Kt
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ln phn chia cho th h I vi DNA lai c t trng nm gia DNA nng N 15 v DNA nh N14. Ni cch khc sau mt ln sao chp phn t DNA mi cha mt na mang N15 v mt na N14. th h II mt na s phn t DNA l lai, na cn li l DNA nh N14. Th nghim ny khng nh gi thuyt ca Watson v Crick l ng tc 2 mch DNA m tch ra, mi ci lm khun tng hp nn mch mi b sung. 4. Din bin sao chp DNA nhim sc th E.coli Qu trnh sao chp DNA E.Coli din ra qua hai giai on: 4.1. Giai on khi s (initiation)
Hnh 2.8 Sao chp DNA vi khun E.coli
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Tai lieu chia se tai: wWw.SinhHoc.edu.vn + M xon:

E.coli qu trnh bt u khi mt protein B c hiu nhn bit im khi s sao chp (replication orgine) ori v gn vo trnh t base c bit . Tip theo enzyme gyrase (mt loi topoisomerase) ct DNA lm tho xon 2 pha ca protein B. Trong khi 2 phn t enzyme gyrase chuyn ng ngc chiu nhau so vi im ori th 2 phn t ca enzyme helicase tham gia tch mch to ch ba sao chp. Helicase s dng nng lng ATP lm t cc lin kt hydro gia 2 base bt cp vi nhau. + Cc protein lm cng mch SSB (single-strand binding protein) gn vo cc mch n DNA lm chng tch nhau, thng ra v ngn khng cho chp li hoc xon vic sao chp c d dng. + Tng hp mi (primer) dc trng cho qu trnh ko di chui l DNA polymerase ch hot ng khi c mi, nn trc khi tng hp chui th phi c qua trnh tng hp mi. Mi l mt on khong 9 -10 nu, c th l DNA hoc ARN. 4.2. Giai on ni di (elongation) Do tnh cht i song song nn khi tch ra thnh 2 mch n khun th mt mch c u 3, mch kia c u 5 nn m bo hng sao chp ca DNA theo chiu 5 -3 th s polymer ha da vo 2 mch khun DNA din ra khc nhau. Mch khun c u 3 c DNA polymerase III gn vo v tng hp ngay mch b sung 5-3 hng vo ch ba sao chp. Mch khun ny c gi l mch khun trc, cn mch mi c tng hp gi l mch trc (leading strand). mch c u 5 (mch khun sau) vic tng hp phc tp hn v thc hin t ch ba sao chp hng ra ngoi m bo ng hng 5-3. Khi mch kp tch ra gn ch ba sao chp , enzyme primase gn mi (primer) ARN khong 10 nucleotid c trnh t b sung vi mch khun. DNA-polymerase III ni theo mi ARN, theo hng ngc vi ch ba sao chp, tng hp cc on ngn 1000-2000 nucleotid, gi l cc on Okazaki (ngi pht hin l Reiji Okazaki). DNA polymerase ni di on Okazaki n khi gp ARN mi pha trc th dng li, ri li ra sau tip tc tng hp t ARN mi mi c to nn gn ch ba sao chp. Tip theo DNA-
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polymerase I nh hot tnh exonuclease 5-3 ct b mi ARN, lp cc nucleotid ca DNA vo ch trng v thc hin polymer ha hng 5 -3. on DNA ngn 10 nucleotid ny cn h 2 u, ch h c ni nh enzyme ligase ca DNA mch c tng hp t ch ba sao chp hng ra ngoi c tng hp chm hn nn gi l mch sau (lagging strand). Qu trnh sao chp DNA E.coli din ra vi tc rt nhanh, c th t n 50.000 nucleotid/pht.
III. Sao chp DNA trong t bo

1. Sao chp nhim sc th Prokaryote theo di sao chp DNA ng v phng x Thymidin (tin cht c hiu cho DNA) c s dng. Qu trnh sao chp xut pht t mt im ori (im xut pht sao chp) v trin khai ra c 2 pha. Khi DNA vng trn ang sao chp, quan st thy dng DNA hnh con mt. Ch ba sao chp lan dn cui cng to ra 2 phn t DNA lai: mt mch c mang du phng x (thymidin-H3). C trng hp sao chp ch xy ra v mt pha. E.coli ch c mt im xut pht sao chp ori nn c phn t DNA thnh mt n v sao chp thng nht c gi l replicon. B gen ca sinh vt tin nhn thng ch c mt replicon.
Hnh 2.9 Sao chp DNA t mt im v 2 pha v v mt pha
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2. Sao chp nhim sc th t bo eukaryote
T bo nhn thc c s lng DNA ln hn nhiu so vi t bo tin nhn, to nn nhiu nhim sc th m mi ci gm mt si DNA thng kt hp vi protein. Do sao chp DNA ca t bo nhn thc phc tp hn v tc chm hn (khong 50 nucleotid/giy).
Hnh 2.10 Sao chp ca nhiu replicon
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Tai lieu cn bnse DNA ca t bo nhn thc c nhiu replicon chia l tai: wWw.SinhHoc.edu.vn im khc
V d: Saccharomyces cerevisiae c ti 500 replicon, tc c 500 im xut pht sao chp. Qu trnh sao chp cng bt u t ori ri lan v 2 pha. T bo c c ch kim sot nghim ngt qu trnh sao chp, im ori no sao chp qua mt ln ri th khng lp li trc khi ton b DNA c sao chp hon ton. cc eukaryote c 5 loi DNA polymerase c k hiu l pol , pol , pol , pol , pol . Cc loi DNA polymerase ny khng ng nht v phn t lng v mt s c tnh ha hc. Pol phn b trong ty th v tham gia ti bn DNA ty th, cc DNA polymerase cn li trong nhn. Trong nhn, DNA polymerase v DNA polymerase l 2 enzyme chnh tham gia tng hp trn si khun dn u v si chm. Pol v tiu n v b ca pol c hot tnh c sa.
Cu hi n tp
1. Hy trnh by th nghim chng minh sao chp DNA theo nguyn tc bn bo ton 2. Sao chp DNA trn 2 mch khun xy ra nh th no? 3. Cc c ch no m bo s n nh rt cao ca thng tin di truyn 4. Hy nu cc nhn t tham gia vo sao chp DNA. 5. Trnh by din bin sao chp DNA nhim sc th E.coli 6. Mc ch ca c ch sao chp t mt phn t DNA cho ra nhiu bn sao
Ti liu tham kho

Phm Thnh H (2000). Di truyn hc. NXB Gio Dc. Nguyn B lc (2004). Acid nucleic v sinh tng hp protein. Trung tm o to T xa, i hc Hu. 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.
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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.
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Chng 3
Tai lieu chia se tai: wWw.SinhHoc.edu.vn C s t bo hc ca tnh di truyn
Mc tiu ca chng
Gii thiu cc cu trc trong t bo c kh nng t ti sinh, chu trnh t bo, cc hnh thc phn bo, cc phng thc sinh sn.
S tit: 3 Ni dung I. Cc cu trc t bo v kh nng t ti sinh

T bo ca nhng sinh vt mc tin ha thp nh vi khun, vi khun lam cha c nhn hon chnh nn gi l t bo tin nhn v nhng sinh vt ny gi l nhng sinh vt tin nhn (Prokaryote). Cc t bo c nhn hnh thnh r rng c gi l t bo nhn thc, c cc sinh vt nhn thc (Eukaryote). S khc nhau gia t bo Prokaryote v Eukaryote ln hn s khc nhau gia t bo ng vt v thc vt. Cc t bo Prokaryote khng c phn ln cc bo quan v mng nhn, c vng tng t nhn gi l nucleoid. Ngoi ra b gen gm DNA khng km histon. im ni bc phn bit t bo Eukaryote l c nhn (nucleus) in hnh vi mng nhn bao quanh. Bn trong t bo c h thng mng phc tp v cc bo quan nh li ni sinh cht, b golgi, lysosome, ty th, lc lp. Nhim sc th ca Eukaryote thng, phc tp c cu to t DNA v protein. 1. Cc cu trc c kh nng t ti sinh Cc t bo Prokaryote c vng nhn cha DNA c ti to v phn u v cc t bo con khi sinh sn. Cc t bo Eukaryote c nhiu bo quan nhng ch c nhn, ty th, lc lp c cha DNA v nh kh nng t ti sinh nn tham gia vo cc c ch di truyn.
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Tai lieu chia se di truyn gi vai tr ch yu trong sinh sn, tai: wWw.SinhHoc.edu.vn Nhn cha thng tin
chim khong 10% th tch v hu nh ton b DNA ca t bo (95%). N c gii hn bi mng nhn do 2 lp mng xp ng tm, bn trong c 2 cu trc ch yu l hch nhn (nucleolus) nh mt nhn nh trong nhn v cht nhim sc (chromatin) l dng tho xon ca nhim sc th (chromosome). S phn chia u NST v cc t bo con m bo s chia u thng tin di truyn cho th h sau. 2. Nhim sc th 2.1. Hnh thi NST
Hnh 3.1. Nhim sc th vi vng tm ng
Khi nhum t bo ang phn chia bng mt s mu base, c th nhn thy di knh hin vi thng cc cu trc hnh que nhum mu m, nn c gi l NST (chromosome). Mi NST c hnh dng c trng, r nht k gia ca nguyn phn. Tm ng l im tht eo chia NST thnh 2 vai vi chiu di khc nhau, vai ngn hn l vai p v vai di hn l vai q. Da vo v tr ca tm ng c th phn bit hnh thi cc NST: - Tm gia (metacentric): 2 vai bng nhau - Tm u (acrocentric): 2 vai khng bng nhau - Tm mt (telocentric): tm ng nm gn cui
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Tai lieu chia dng (soma), mi NST c mt cp ging nhau v se tai: wWw.SinhHoc.edu.vn cc t bo sinh
hnh thi, c gi l cc NST tng ng (homologous). B NST c cp gi l lng bi v khi mi NST ch c mt chic gi l n bi.
Hnh 3.2 S cc kiu nhim sc th k gia v k sau
2.2. Kiu nhn v nhim sc : Tt c cc t bo ca mt loi ni chung c s lng NST c trng cho loi . Mi loi NST c hnh dng c trng. S m t hnh thi ca NST gi l kiu nhn (Karyotype). Kiu nhn c th biu hin dng nhim sc (Idiogram) khi cc NST c xp theo th t bt u t di nht n ngn nht.
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hon chnh lm r hn cc vt c trng, hnh thi ca mi NST c xc nh chi tit hn. Da vo nhim sc nhum mu, c th tm thy cc on tng ng trn cc NST cng loi ca cc loi c h hng gn nhau. V d so snh nhim sc ca ngi v vn cho thy c mi quan h h hng rt gn v NST th hai ca ngi do s ni li ca 2 NST khc nhau vn ngi.
Tai ny kchia se tai: mu (mu giemsa hay quinacrin) lieu thut nhum wWw.SinhHoc.edu.vn Sau
Hnh 3.3 Cp nhim sc th tng ng
2.3. Cht nhim sc Vo nhng nm 1930, khi quan st bng knh hin vi quang hc gian k nhn thy trn NST c vng nhum mu m c gi l cht d nhim sc (heterochromatin) phn bit vi phn cn li nhum mu nht l cht nguyn nhim sc (euchromatin). Cht nguyn nhim sc l cht nhim sc trng thi dn xon, cn cht d nhim sc l cht nhim sc biu hin dng cun xon cao. DNA cht nguyn nhim sc trng thi hot ng, cn cht d nhim sc th DNA khng phin m c v thng sao chp mun hn.
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Hnh 3.4 S phn ha cc phn trn nhim sc th
3. Cc nhim sc th c bit Bng cc k thut t bo hc hin i, cn c cc mt chc nng, cu trc, hnh thi v c th trong hot ng, ngi ta phn bit cc loi NST khc nhau: - Nhim sc th thng (NST A: autosome): ging nhau c 2 gii c, ci. - Nhim sc th gii tnh (sex chromosome) khc nhau gia gii c v ci - Nhim sc th B (nhim sc th ph): c pht hin mt s loi thc vt nh ng, mch en ngoi cc NST A bnh thng. Cc NST B t gp hn trong cc ging c chn lc ca cc loi ni trn ng c 20 NST A, mt s cy cn c thm NST B vi s lng bin ng t 1-20 hoc nhiu hn. Nhng cy c NST B th yu hn v km hu th hn cc cy khc. mch en, nhng cy c hn 9 NST B thng khng c kh nng sng. NST B c hiu qu di truyn rt thp. NST B cng c nhiu su b, giun dp nhng b v khng c hiu qu di truyn r rt. - NST khng l (polytene chromosome): c trong mt s c quan, t bo tuyn nc bt, tuyn Manpighi, mng rut mt s cn trng b 2 cnh (Diptera): Drosophilidae, Chironomidae.
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Tai lieu chia se tai: wWw.SinhHoc.edu.vn bt u Nm 1981, E. Balbiani pht hin NST khng l tuyn nc
trng Chironomus, chng c s lng si nhim sc nhiu gp hng ngn ln so vi NST thng, c th cha ti 1500-1600 si nhim sc. Nguyn nhn ca hin tng ny l do c ch ni nguyn phn (endomitosis). NST t nhn i bnh thng, nhng khng phn ly, nhn t bo khng phn chia, to NST c dng chm nhiu si, b ngang ca NST tng ln. Chiu di ca NST khng l c th ti 250-300 m (gp 100-200 ln NST thng) do cc NST th ny khng ng xon. Dc theo chiu di ca NST khng lphn ha thnh nhng khoanh bt mu xm, nht khng ng nht nh cc a sng, ti xen nhau. Ngi ta cho rng cc a xm mu l ni tch ly nhiu DNA, c to ra do xon nh khu dy c hoc do tp trung nhiu ht nhim sc.
Hinh 3.5. Nhim sc th khng l cua rui gim
rui gim, NST khng l tuyn nc bt c hnh thnh do DNA t nhn i 10 ln, to ra 210 = 1024 si dnh lin nhau sut dc theo chiu di. - NST chi n (lambrush chromosome): NST ny c th di n 800m, c tin k ca gim phn trong t bo trng ca ng vt c xng sng nht l giai on Diplotene ca trng c nhiu non hong (trng g, chim hoc b st).
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Tai lieu chia se tai: wWw.SinhHoc.edu.vn a. c.
b.
Hinh 3.6 Nhim sc th khng l rui gim (a) Nhim sc th khng l cua rui gim tao tm sc (chromocenter) (b) B nhim sc th c ban trong t bao ang phn chia vi cac nhanh c biu hin bng cac mau khac nhau (c) Anh chup nhim sc th khng l
Hinh 3.7 Nhim sc th chi en
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Tai im ca NSTse tai: wWw.SinhHoc.edu.vn vng lieu chia kiu chi n l t trc ca NST c nhiu c
DNA, cnh cc vng DNA ny l nhng loi ARN c tng hp t cc vng DNA m xon.
II. Chu trnh t bo v phn bo Eukaryote

1. Chu trnh t bo
Hnh 3.8 Chu trnh t bo
Cc t bo ca sinh vt Eukaryote tri qua nhiu giai on ni tip nhau v kt thc bng s phn chia to ra t bo mi. Ton b qu trnh t t bo n t bo th h k tip c gi l chu trnh t bo, gm 4 giai
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on: M, G1, S v G2. S phn chia t bo ch chim mt phn ca chu trnh t bo - M (Mitose) l giai on nguyn phn - Giai on G1 (Gap): ko di t sau khi t bo phn chia n bt u sao chp vt cht di truyn. S tch ly vt cht ni bo n mt lc no t im ti hn th t bo bt u tng hp DNA - S (Synthesis) l giai on tng hp DNA. Cui giai on ny s lng DNA tng gp i - G2 l giai on c ni tip sau S n bt u phn chia t bo. Khong thi gian gm G1, S v G2 t bo khng phn chia v c gi chung l gin k hay k trung gian (interphase). Trong k ny t bo thc hin cc hot ng sng ch yu khc v sao chp b my di truyn. 2. Nguyn phn (Mitosis) S phn bo sinh vt nhn thc gm 2 qu trnh: chia nhn (mitosis) v chia t bo cht (cytokinesis) Nguyn phn c chia thnh 4 k: a. K trc (Prophase) Cc trung th (centriole) chuyn ng v 2 cc ca nhn, cc NST co li thnh si. Mi NST gm 2 si chromatid gn nhau nh tm ng (centromere). Cc si v sc ta ra t tm ng v trung th. Mng nhn v hch nhn bin mt dn. Cc t bo thc vt khc vi t bo ng vt l khng c trung th v thoi v sc. b. K gia (Metaphase) Tm ng ca mi NST i gn vi thoi v sc v xp mt phng xch o ca t bo. K gia chm dt khi mi tm ng ca mi chromatid ch em bt u tch ra. Nh vy tm ng l im chia cui cng ca NST. iu ny c ngha rt quan trng, nh cht di truyn c chia u v ng b cho cc t bo con. c. K sau (Anaphase) Hai NST n tch nhau, mi ci chuyn ng v mt cc t bo. Cc si v sc co ngn li ko cc NST. S phn chia t bo cht thng bt u k ny.
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Tai lieu(Telophase) tai: wWw.SinhHoc.edu.vn chia se d. K cui

Cc NST di chuyn v cc cc, mng nhn v hch nhn li hnh thnh, s chia t bo cht thc hin xong, cc NST dn ra v mnh dn. S phn chia t bo cht: thng km theo ngay sau gim phn. t bo ng vt s chia t bo cht bt u bng np nhn phn cch (cleavage furrow) bao vng t bo v mc su dn n chia t bo thnh hai. t bo thc vt, phin t bo (cell plate) hnh thnh trung tm t bo cht v lan rng dn n ct t bo thnh hai. Nguyn phn to ra 2 t bo con c s lng v cht lng NST nh t bo m.
Hnh 3.9 Phn bo nguyn nhim
3. Gim phn (meiosis): l qu trnh phn bo chuyn bit trong s lng NST gim mt na nhng b, xy ra t bo sinh dc. Gim phn tri qua 2 ln phn chia ni tip nhau:
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Hnh 3.10 Phn bo gim nhim
Gim nhim I: a. K trc I (Prophase I) Cc s kin xy ra ging k trc ca nguyn phn ch khc cn bn ch cc NST tng ng cng chuyn ng vi nhau v nm k sng i
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nhau trong qu trnh bt cp hay tip hp (synapsis). Cc si nhim sc chi em c gn nh nhau nh mt cp protein trc (protein axe). Cc protein trc ca 2 NST tng ng ni nhau bi cu protein to nn phc hp bt cp (synaptonemal complex). Cp NST tng ng lc ny to thnh i gi l lng tr (bivalent). Cc NST sau khi tip hp xong bt u tch ra, c th quan st thy cc on an cho nhau gi l hnh cho (chiasma). Cc hnh cho gia cc chromatid c th xy ra trao i cho dnh nhau.
Hnh 3.11 Cc qu trnh xy ra trong k u I phn bo gim nhim
b. K gia I (Metaphase I) Hai NST ca mt cp tng ng gn vi cng mt si ca thoi v sc trn mt phng xch o ca t bo. Cc tm ng khng tch ra. c. K sau I (Anaphase I) Hai NST ca mi cp tip hp chuyn ng v 2 cc i nhau. d. K cui I (telophase I)
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Tai nhn mi c hnh thnh, mi ci vi na b NST (n) c t lieu chia se tai: wWw.SinhHoc.edu.vn Hai
bo m. Cc nhn con c s lng NST bng nhau nhng kiu gen khng tng t nhau. Tip theo l thi k gin k rt ngn, trong k ny khng xy ra sao chp vt cht di truyn. Gim nhim II: e. K trc II (Prophase II): Cc NST co li f. K gia II (Prophase II): Cc NST xp trn mt phng xch o, thng cc chromatid tch nhau mt phn g. K sau II (Anaphase II): Cc tm ng phn chia, cc chromatid y nhau v cc cc. h. K cui II (Telophase II): 4 t bo n bi cha cc NST n c to thnh. Nh vy gim nhim I to 2 t bo n bi cha NST i, mi t bo li chia ln na trong gim nhim II to ra 4 t bo n bi cha cc NST n. - Phn bo gim phn c ngha rt quan trng + m bo s lng NST trong sinh sn hu tnh khng thay i. + m bo cho s to thnh ca cc t bo sinh dc khc nhau. +To NST c thnh phn mi do ti t hp gia cc NST b m. So snh nguyn phn v gim phn Ging nhau - Sao chp DNA trc khi vo phn bo - u phn thnh 4 k - S phn u mi loi NST v cc t bo con - Mng nhn v nhn con bin mt cho n gn cui - Hnh thnh thoi v sc
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Khc nhau

Gim phn (Meiose) 1. Xy ra t bo sinh dc 2. Hai ln phn chia to 4 t bo con
So snh cc c tnh ch yu ca nguyn phn v gim phn Nguyn phn (Mitose) 1. Xy ra t bo soma 2. Mt ln phn bo: 2 t bo con
3. S NST gi nguyn: 1 t bo 2n 3. S NST gim i mt na: 1 t 2 t bo 2n bo 2n 4 t bo n 4. Mt ln sao chp DNA , mt ln 4. Mt ln sao chp DNA , 2 ln chia chia 5. Thng cc NST tng ng 5. Cc NST tng ng bt cp khng bt cp k trc I 6. Thng khng c trao i cho 7. Tm ng chia k sau 6. nht 1 trao i cho cho 1 cp tng ng 7. Tm ng khng chia k sau I m chia k sau II
8. Duy tr s ging nhau: t bo con 8. To s a dng trong cc sn c kiu gen ging kiu gen t bo phm ca gim phn 9. Gim phn lun lun xy ra t m 9. T bo chia nguyn phn c th l bo lng bi (2n) hoc a bi (>2n) lng bi (2n) hay n bi (n) S khc nhau th hin nhiu chi tit. ng lu l trong k trc I ca gim phn, cc NST tng ng bt cp ri sau y nhau ra i v cc cc. Nh mi t bo con trong gim phn ch nhn 1 NST ca cp tng ng. S kin ny tng ng vi vic tm ng gia 2 chromatid ch em cng i vi nhau trong nguyn phn v khi tm ng chia th mi t bo con ch nhn 1 chromatid. C ch thc hin tuy c khc nhau nhng ging nhau ch chia u mt cch ng b cc NST v cc t bo con.
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Hnh 3.12 So snh nguyn phn v gim phn
S bin i trong qu trnh phn bo
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Tai lieu chia se tai: wWw.SinhHoc.edu.vn i, - Hnh thnh NST khng l: vo k trc, sau khi DNA t nhn
hnh thnh cc nhim sc t, nhng sau chng khng tch ri nhau. - Ni nguyn phn: tin k, mng nhn khng tiu bin, qu trnh phn chia s xy ra bn trong mng nhn. Kt qu to ra nhn mi c b NST tng gp i. - Hnh thnh th a bi: Sau khi NST t nhn i, mng nhn tiu bin nhng thoi v sc khng xut hin, to ra nhng t bo c s lng NST tng gp bi. - T bo 2 nhn: sau khi phn chia nhn, t bo cht khng phn chia hnh thnh t bo mi c hai nhn. Trong gim phn cng xy ra nhng bin i: do s tip hp v phn ly khng bnh thng ca cc NST, c th lm pht sinh cc giao t tha hoc thiu NST. C trng hp thoi v sc khng xut hin, s to thnh cc giao t khng gim nhim.
III. Cc kiu sinh sn

1.Sinh sn v tnh Sinh sn v tnh l kiu sinh sn t mt t bo hoc mt nhm t bo m ch qua nguyn phn to ra cc c th con. Kiu sinh sn ny gi nguyn cc c tnh di truyn ca c th m ban u c th con. Nguyn phn l c s ca s tng trng cc sinh vt a bo v sinh sn v tnh cc sinh vt ni chung. Sinh sn v tnh c c sinh vt n bi v lng bi, l c ch n nh b gen qua nhiu th h. S tng s lng t bo ca sinh vt a bo nh nguyn phn. ngi hp t sau nhiu ln nguyn phn hnh thnh nn c th gm nhiu t t bo. Nh , tr t bo sinh dc cc t bo ca c th u c b NST nh nhau, tng ng c lng thng tin di truyn ging nhau. Sinh sn v tnh c ng dng rng ri trong nhn ging v nui cy m t bo thc vt v ng vt. 2. Sinh sn hu tnh Sinh sn hu tnh l kiu sinh sn trong c s kt hp cc t bo sinh dc ca 2 c th khc nhau. Sinh sn hu tnh to s a dng di truyn
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lm ngun nguyn liu cho tin ha. Mt trong nhng xu hng tin ha ca sinh gii l sinh sn hu tnh. S a dng ca cc kiu sinh sn hu tnh th hin mt phn cc kiu xc nh gii tnh. S tin ha to ra nhiu c ch duy tr s a dng. * Hng tin ha trong sinh sn hu tnh Theo s phn ha t bo, c 3 hng tin ha: + Hnh thi cc giao t: theo hnh thi giao t, sinh vt tin ha t ch giao t c v giao t ci u c hnh thi v chc nng ging nhau (ng giao) n ch khc nhau: giao t c nh c kh nng di ng, giao t ci ln cha cc cht dinh dng (d giao v non giao) + Theo s phn ha ca cc t bo trong c th: t ch t bo no trong c th cng c kh nng lm nhim v sinh sn n ch phn ha thnh t bo sinh sc v t bo sinh dng. + Phn ha gii tnh: a s thc vt v ng vt bc thp, c quan sinh dc c, ci ngay trn mt c th, gi l sinh vt lng tnh. mt s thc vt v ng vt bc cao, mi c th ch mang mt c quan sinh dc (hoc c hoc ci) gi l sinh vt n tnh. Theo hnh thc th tinh cc ng vt bc thp c bit l ng vt thy sinh, tinh trng c th tinh vi trng ngoi mi trng nn hiu qu th tinh thp. Hnh thc th tinh ny c gi l th tinh ngoi. V d: rut ti, c ... chng phng tinh vo nc th tinh, lng c (ch nhi) con c ri tinh trng ln trng ca con ci. Hnh thc th tinh cao hn l th tinh trong. Phn ln cc loi cn, con c a tinh trng vo ng sinh dc ci nh c quan giao cu, nh vy hiu sut th tinh cao hn. Theo hnh thc bo v trng Cc loi ng vt bc thp trng nc v t c kh nng bo v trng nh c, lng c. Cc loi b st nh rn trng c v bo v bo thai. Cc loi chim c bn nng bo v trng tt hn, lm t, trng, p trng v chm sc chim non. Cc loi c v, trng khng ra ngoi, bo thai pht trin trong t cung m, phi thai c bo v chu o chng nhng tc hi ca ngoi cnh, sau khi , con c m cho b ti khi c kh nng t kim n.
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3. Cc hnh thc sinh sn c bit - Lng tnh sinh
Phn ln cc loi thc vt v nhng ng vt lng tnh, trn mt c th c c c quan sinh dc c v c quan sinh dc ci. Qu trnh th tinh, th phn c th l t th tinh, t th phn hay th tinh, th phn cho. V d sn dy, trong rut ngi b mc sn dy ch c mt con sn. C th sn dy c nhiu t, mi t c c c quan sinh dc c v c quan sinh dc ci. Cc t gn u, c quan sinh dc c pht trin mnh, cc t cui c quan sinh dc ci pht trin mnh. Khi th tinh, cc t gn u p vo cc t gn cui c th th tinh cho cc t nh c quan giao cu. a s ng vt lng tnh khng t th tinh c m hai c th khc nhau giao hp cho cho nhau nh sn l, giun t. a s cc loi thc vt l cc loi lng tnh. Cc loi lng tnh ny thng th phn cho nhng cng c mt s loi c cu to thch nghi vi t th phn. - n tnh sinh n tnh sinh (cn gi l trinh sn) l hnh thc sinh sn trong trng khng th tinh vn pht trin thnh c th sinh vt. n tnh sinh khc vi sinh sn v tnh v trng y vn c hnh thnh t qu trnh gim phn ca t bo sinh dc. V mt di truyn, ngi ta phn ra 2 loi n tnh sinh: l n tnh sinh n bi trong c th n tnh sinh trng thnh gi nguyn b NST 1n trng khng th tinh; loi n tnh sinh lng bi c s to b NST 2n nhng b gen ny u ly t mt ngun t m (cc gen thng ng hp t). Lin quan n gii tnh, phn bit 3 loi n tnh sinh: + n tnh sinh nam Kiu n tnh sinh ny gp nhiu loi ong nn cn gi l n tnh sinh kiu ong + n tnh sinh n nhiu vng, mt s loi ng vt ch c con ci khng c con c nh mt s loi c, tm, cua ... chng vn trng v n ton c th ci. C nhiu c ch to t bo 2n ca c th mi trong n tnh sinh:
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T bo sinh dc ci khi gim phn t bo cht khng phn chia to t bo 2n NST, n ra c th ci. T bo sinh dc ci gim phn bnh thng nhng th cc II li ha hp vi non bo to t bo 2n NST, n ra c th ci. + n tnh sinh chu k Nhiu loi sinh vt c ma sinh sn hu tnh, c ma sinh sn v tnh. V d: lun trng Rotatoria v ma xun, t nhng trng nm sut ma ng s n ra nhng con ci sinh sn n tnh sinh n, trng khng th tinh ca n s n ra con ci. V sau, n thi k sinh sn hu tnh, mt th h s thay i li sinh sn trng nh hn, n ra con c (n tnh sinh nam), con c s giao phi vi nhng con ci th h m. Nhng con ci s ra nhng trng th tinh c kh nng sng qua ma ng, trng c 2n NST, n ma xun s n ra con ci tip tc sinh sn n tnh sinh nh trn. + n tnh sinh nhn to Trng ca cc loi khng sinh sn n tnh c th dng phng php nhn to cho trng pht trin m khng cn th tinh. Trng ch c th kch thch bng chm kim, trng ca cu gai c th kch thch bng cch lc hoc bng cht ha hc nh thay i m mui ca nc. Cc loi sinh sn n tnh nhn to thng yu, nh hn bnh thng v khng pht trin y . + n tnh sinh ngi ngi gp trng hp trng khng th tinh m phn chia thnh 50 phi bo. Bung trng c th c cc u nang, bn trong cha mt s b phn ca c th pht trin khng y v sp xp ln xn nh tc, rng, tay, mt, chn ... nhng u ny gi l u qui. Ngi ta cho rng nang sinh ra bi s pht trin bt thng ca trng khng th tinh. - Mu sinh: Mu sinh l hin tng sinh sn da trn s pht trin ca trng c th tinh nhng sau nhn tinh trng b mt hot tnh v b loi b, ch c nhn ca trng tham gia vo qu trnh pht trin to c th mi. Hin tng ny gp mt s loi c, v d c dic bc mu sinh t nhin to cc c dic bc ci. sinh sn c dic bc ci phi giao phi vi c chp c hoc c dic
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vng c hoc mt s c c khc. Tinh trng ch c chc nng hot ha trng, sau nhn tinh trng thoi ha v tiu bin. Mu sinh nhn to c s dng trong chn ging. - Ph sinh: Ph sinh l hnh thc sinh sn da trn s pht trin ca trng c th tinh nhng sau nhn trng b thoi ha, ch c nhn tinh trng tham gia vo qu trnh pht trin to c th mi. Ph sinh nhn to c ng dng to ra nhng ging tm cao sn. 4. Chu trnh sng hay vng i Nhiu sinh vt c s thay i th h n bi v lng bi ni tip nhau thnh chu k gi l chu trnh sng. Vng i in hnh ca Eukaryote in hnh gm: th tinh c hp t bo cht v hp nhn, sinh sn v tnh ca t bo 2n nh nguyn phn, gim phn c gim nhim v ti t hp, cc t bo n sinh sn v tnh hoc kt hp vi nhau th tinh. S a dng cc chu trnh sng cc nhm phn loi khc nhau c th do thi gian ko di khc nhau ca cc pha n bi v lng bi. Cc nhm chnh thng gp trong nghin cu di truyn: a. Cc Eukaryote n bo: nh chu trnh sng ca vi to nh Chlamydomonas reinhardi. im c bit l cc giai on n bi v lng bi c th tn ti mt thi gian di. b. Cc ng vt bc cao: c th ng vt bc cao l lng bi. Trong qu trnh sinh sn phn bo gim nhim to ra giao t n bi, s hp nht ca chng to thnh hp t. Cc giao t l nhng t bo n bi c chuyn ha cho sinh sn hu tnh. con c, qu trnh sinh tinh (spermatogenesis) to ra 4 tinh t. con ci, qu trnh sinh trng (oogenesis) ch sinh ra mt t bo trng trng thnh, cc th phn cc khng c hot ng chc nng. c. Chu trnh sng ca thc vt bc cao. Chu trnh sng ca cy bp c coi l in hnh ca thc vt bc cao. Phn bo gim nhim thc vt to ra cc t bo n bi gi l bo t giai on I, m chng thng phn chia nguyn nhim to to cy a bo n bi (giai on II). Cc thc vt n bi ny sn sinh ra cc giao t bng chia nguyn nhim (giai on III). Hai giao t khc nhau to hp t lng bi
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(giai on IV), hp t pht trin thnh cy a bo lng bi (giai on V) v chu trnh khp kn. Phn ln cc thc vt a bo c 5 giai on trong chu trnh sng ca chng. Ni chung, giai on n bi chim u th thc vt bc thp v giai on lng bi chim u th cc thc vt bc cao. Kh nng cc giao t c sn sinh ra do mt cy, kt hp vi nhau to th h con c sc sng v hu th l c tnh chung ca nhiu h cy c hoa. Cc hoa hon chnh ca mt s thc vt ng chu m ra cho n khi ht phn chn v t th phn. T th phn l bt buc i mch, u, u nnh, thuc l, c chua, la m la nc v nhiu cy trng khc. mt s loi khc, t th phn v th phn cho xy ra vi cc mc dao ng khc nhau. V d: cy bng vi thng hn 10% th phn cho. Trong khi , mt s thc vt ng chu c s pht trin cc c ch di truyn ngn tr s t th phn, tc ngn tr s to thnh hp t ca cc giao t ging nhau v kiu gen, gy nn th phn cho bt buc. S t bt dung hp cc loi ng chu l c ch tng cng th phn cho.
Cu hi n tp
1. S khc nhau gia nhim sc th v nhim sc t 2. S khc nhau gia chromatid ch em v chromatid khng ch em, gia nhim sc th tng ng v nhim sc th khng tng ng 3, Trong sut chu trnh t bo, s sao chp nhim sc th xy ra khi no. ngha ca n. 4. So snh nguyn phn v gim phn. 5. ngha ca cc s kin din ra k u ca ln gim phn th nht. 6. Trnh by cc hnh thc sinh sn c bit.
Ti liu tham kho

Trnh Vn Bo, Phan Th Hoan, Trn Th Thanh Hng, Trn Th lin, Trn c Phn, Phm c Phng, Nguyn Vn Rc, Nguyn Th Trang. 2002. Cc nguyn l sinh hc. NXB Y hc H Ni. Phm Thnh H (2000). Di truyn hc. NXB Gio Dc.
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Nguyn B lc (2004). Acid nucleic v sinh tng hp protein. Trung tm o to T xa, i hc Hu. 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. 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.
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Chng 4
Tai lieu chia se tai: wWw.SinhHoc.edu.vn Cc quy lut di truyn ca Mendel
Mc tiu ca chng
Gii thiu quy lut Mendel v s di truyn, s phn ly kiu hnh trong trng hp tnh tri hon ton v tri khng hon ton v mt s tnh trng di truyn kiu Mendel.
S tit: 3 Ni dung I. Phng php th nghim ca Mendel

1. Tnh trng hay du hiu (character) Thng thng, khi quan st cc sinh vt khc nhau s c nhng nt m nh chng ta d dng nhn bit ta gi n l tnh trng (hay du hiu) + C nhng tnh trng thuc v hnh thi: mu mt , mu tc, mu da...
Hinh 4.1 Bay cp tinh trang u Ha lan c Mendel chon nghin cu
+ C nhng tnh trng thuc v sinh l, sinh ha nh: kh nng thc hin ca mt phn ng, kh nng thc thin chuyn ha ...
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Tai lieu chia se thuc wWw.SinhHoc.edu.vn tai: v tnh cht: tnh tnh + C nhng tnh trng
Mendel chn ra 7 cp tnh trng cht lng c biu hin r rng nghin cu. Hin nay bit 7 cp tnh trng m Mendel nghin cu ch nm trn 4 cp NST ca cy u H lan. Cc gen xc nh tnh trng mu nhn ht v v ht, hnh dng qu v v tr hoa thuc 2 nhm lin kt gen, nhng chng nm cch xa nhau nn kt qu thu c nh trng hp khng lin kt.
Hinh 4.2 Con lai thu c nh lai cp b m vi cc tinh trang tng phan
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2. Cch tin hnh th nghim:
- Vt liu thun chng v bit r ngun gc. Mendel cho cc cy th nghim t th phn trong 2-3 i. - Theo di tng cp tnh trng qua nhiu th h ni tip nhau. Trong c nhng tnh trng c nh gi ngay nhng cng c nhng tnh trng theo di tip th h sau. - nh gi khch quan v tnh s lng chnh xc. Mendel quan st tt c cc ht v con lai xut hin, thng k s lng v tnh t l tng loi - Dng k hiu v cng thc ton hc biu din kt qu th nghim. Mendel tm ra phng php n gin biu din cc dng bng cng thc s hc.
Hinh 4.3 i tng thi nghim cua Mendel (a) Cy co hoa trng (b) Hat phn c tao thanh trong bao phn (c) Ngn can s t thu phn, bng ct bo bao phn cy me va cho thu phn vi bao phn cua cy b
n u th k 20, s truyn th cc tnh trng di truyn c pht biu thnh 3 quy lut Mendel: quy lut tnh tri, quy lut phn ly tnh trng v quy lut phn li c lp. Quy lut th nht v th hai pht biu theo cch ny thiu chnh xc v: + Phi c cc iu kin nh thun chng v tri hon ton. + ng mt phn cho di truyn tng ng v tri khng hon ton.
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Tai lieu chia se tai: wWw.SinhHoc.edu.vn + Khng dng c cho phn li giao t v sinh vt n bi.
Sau ny a s cc nh di truyn pht biu li thnh 2 quy lut: + Quy lut th nht: quy lut phn li hay quy lut giao t thun khit + Quy lut th hai: quy lut phn li c lp.
II. Lai mt tnh trng-Quy lut giao t thun khit.

Lai mt tnh l php lai m ch theo di mt cp tnh trng 1.Th nghim : P lai u H Lan ht vng vi ht lc F1: F2: 100% u ht vng. 3 vng : 1 lc
Hnh 4.4 S m t php lai mt tnh
Tnh trng ht vng c biu hin th h F1 c gi l tnh trng tri (dominant) v gen quy nh n c k hiu bng ch A, tnh trng ht lc gi l ln (recessive) v gen quy nh n c k hiu bng ch a. d dng theo di F2, nh di truyn hc ngi Anh R.C Punnett a ra khung k c gi l khung Punnett n nay vn c s dng.
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2. Gii thch ca Mendel:
ng cho rng mi tnh trng do mt cp nhn t kim tra v mi c th c 2 nhn t : mt nhn t cha v mt nhn t m. Mendel dng khi nim nhn t di truyn ch cc nhn t ny, giao t ch cha mt nhn t v con lai s to ra 2 loi giao t. chng minh iu ny, ng em lai phn tch (Test cross) F1 F1 : Aa x aa 1Aa : 1aa Hin nay gen c hiu l nhn t di truyn xc nh cc tnh trng ca sinh vt nh hnh dng, mu sc... Khi nim alelle c nu ra ch cc trng thi khc nhau ca mt gen. Cc th c 2 alelle ging nhau nh AA v aa c gi l ng hp t (homozygote), cn c th mang hai alelle khc nhau gi l d hp t (heterozygote). - Kiu gen: tp hp cc nhn t di truyn ca c th - Kiu hnh: biu hin ra bn ngoi ca tnh trng, n l kt qu ca s tng tc gia kiu gen vi mi trng bn ngoi. 3.Tnh tri khng hon ton v s di truyn tng ng. cy hoa mom cho, khi lai cy co hoa o vi cy co hoa trng co kt qu: P: hoa x hoa trng AA aa F1: Aa (hoa hng) F2: 1 AA : 2Aa : 1 aa 1 : 2 hng : 1 trng trng hp ng tri, con lai F1 biu hin cc tnh trng ging c b v m. Trong trng hp ny tnh tri khng hon ton v t l phn ly kiu gen bng t l phn ly kiu hnh. Php lai gia ht u lng c vt khoang thun chng vi ht c nhiu m thun chng sinh ra con lai d hp t c c cc m v vt khoang. Bi v mi kiu gen u t n biu hin ra kiu hnh, t l F 2 l 1:2:1.
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Hinh 4.5 S php lai mt tinh vi tinh tri khng hoan toan hoa mom cho
Hinh 4.6 S php lai mt tinh vi tinh tri khng hoan toan vo hat u lng
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Taidilieu chia se tai: khi 2 alelle c gi tr nh nhau. nhm wWw.SinhHoc.edu.vn S truyn tng ng:
mu ABO ca ngi, IA v IB u c biu hin nh nhau.
Hinh 4.4 Cc allele nhom mu IA v IB l ng tri bi v t bo hng cu cha d hp t IAIB cha c 2 dng ng trn b mt ca chng 4. C s t bo hc Theo di s truyn t alelle qua cc th h NST trong phn bo gim nhim ri cc giao t c th tinh thy c s trng hp. 5. Th nghim chng minh trc tip s phn ly mc giao t Kt qu lai phn tch cho t l 1:1 chng t c s phn li khi to thnh giao t. Nhng kt qu ny gin tip v ta ch quan st kt qu c th lng bi. chng minh trc tip s phn li khi to thnh giao t, cho lai bp t vi bp np ri xem t l phn li phn hoa. Gen Wx (quy nh bp t) to tinh bt s cho mu xanh khi phn ng vi iod, cn gen wx (bp np) cho mu hng nu. Ly phn hoa ca cy lai
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Wxwx th iod v quan st di knh hin vi thy t l ht nhn xanh v hng nu l 1:1. Kt qu ny chng t cc quy lut ca Mendel c c s khoa hc l s phn li khi to thnh giao t. 6. Quy lut th nht (quy lut giao t thun khit): trong c th cc gen tn ti theo tng i, khi to thnh giao t tng i gen phn li nhau v mi gen i vo mt giao t. Sau khi 2 giao t phi hp nhau cc gen tng ng li hp thnh tng i trong hp t. Quy lut ny p dng cho cc sinh vt lng bi (2n NST). i vi cc sinh vt n bi th t l phn li ging nh lai phn tch.
III. Lai hai tnh v nhiu tnh

1. Lai hai tnh - Quy lut phn ly c lp v t hp t do Lai 2 tnh l lai vi 2 cp tnh trng Th nghim : P: F1: ht vng trn x AABB vng trn AaBb AaBb F1 x F1: vng trn vng trn AaBb F2: 4AaBb : 2 AaBB : 2Aabb : 2 AABb: 2aaBb : 1AABB : 1 Aabb: 1aaBB: 1aabb ( 9 kiu gen) Kiu hnh: 9A -B- : 3A-bb : 3aaB- : 1aabb 9 vng trn : 3 vng nhn : 3 lc trn : 1 lc nhn Xt t l: vng / lc = 12 /4 =3/1 trn / nhn = 12/ 4 =3/1 Kt qu th nghim cho thy th h F1 cng ng nht v biu hin cc tnh trng tri vng trn. Sang F2 t l phn li kiu hnh l: 9 vng trn : 3 vng nhn : 3 lc trn : 1 lc nhn. Xt ring tng cp tnh trng, t l phn li theo kiu hnh cng l 3:1. iu cho thy s di truyn tng cp ht lc nhn aabb
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tnh trng c lp nhau. S c lp ny c th chng minh bng ton hc v xc sut ca 2 s kin c lp vi nhau cng trng hp bng tch xc sut ca 2 s kin . T l phn li ca cp vng - lc l 3/4 vng : 1/4 lc v ca cp trn - nhn l 3/4 trn : 1/4 nhn. T hp ca tnh trng trn vng s c xc sut l: 3/4 3/4 = 9/16, trn xanh: 3/4 1/4 = 3/16, vng nhn: 3/4 1/4 = 3/16, lc nhn: 1/4 1/4 = 1/16
Hnh 4.5 S m t php lai hai cp tnh trng
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Quy lut th hai ca Mendel: (quy lut phn ly c lp v t hp t do): Cc gen ca tng cp trong phn bo gim nhim phn ly nhau c lp vi cc thnh vin ca cc cp gen khc v chng hp li trong cc giao t ang c hnh thnh mt cch ngu nhin. 2. Lai vi nhiu cp tnh trng Cng thc chung ca lai nhiu tnh: S cp gen d hp t F1 1 2 3 ... n 2n 4n 3n 2n s loi giao t 2 22 = 4 23 = 8 s loi t hp F2 4 42 = 16 43 = 64 s kiu gen F2 3 32 = 9 33 = 27 S kiu hnh F2 2 22 = 4 23 =8
C th lai vi 3 cp tnh trng hoc nhiu hn. P: G: F1: F1 F1: AaBbDd AABBDD ABD x x abd AaBbDd AaBbDd aabbdd
G: ABD, AbD, ABd, aBD, Abd, abD, aBd,abd. F2: S phn ly kiu hnh theo t l: 27 A-B-D- : 9A-B-dd : 9A-bbD- : 9aaB-D-: 9A-bbdd : 3aaB-dd : 3aabbD- : 1aabbdd 3. Mt s tnh trng Mendel ngi: Rt nhiu tnh trng ca ngi c s di truyn theo cc quy lut Mendel. Mt s tnh trng thng gp: khp ngn ci ngc ra pha sau c hay khng, tc mc thnh nh nhn trn, nhiu tn nhan, lm ng tin trn g m, bch tng, di tai ngi c th thng hay lin (di tai thng l tri). C 2 gen tri nh hng n kh nng cun li, mt gen to kh nng cun li trn v gen tri th hai cho php gp ngc.
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Tai lieu chia sedi truyn gen tri trn NST thng tai: wWw.SinhHoc.edu.vn * c im ca bnh
Cc bnh di truyn gen tri trn NST thng c gp vi tn s 1/200 c th. V d: tt tha ngn sau trc (postaxial polydactyly) vi biu hin tha ngn cnh ngn t. Tt ny di truyn kiu tri trn NST thng. Trong gen A quy nh tha ngn, a quy nh ngn bnh thng. c im quan trng ca cc bnh di truyn do gen tri trn NST thng: - C 2 gii u c t l mc bnh ngang nhau. - Khng c s gin on gia cc th h. - Ngi mang gen bnh trng thi d hp kt hn vi ngi bnh thng s truyn cho con ca h vi xc sut l 1/2. * c im ca bnh di truyn gen ln trn NST thng V d: Bnh bch tng l mt bnh di truyn gen ln gy ra do t bin gen m ha enzyme chuyn ha tyrosine. S thiu ht enzyme ny lm nh tr qu trnh chuyn ha tng hp sc t melanin. Ngi mc bnh s c rt t sc t da, tc v mt. V melanin cng cn cho s pht trin ca cc si thn kinh th gic nn ngi mc bnh bch tng cng c th b tt rung git nhn cu, lc mt gim th lc. c im chnh ca bnh di truyn do gen ln trn NST thng: - Bnh thng c thy mt hoc mt s anh ch em rut nhng li khng c th h b m. - Mt cp v chng mang gen bnh s c trung bnh 1/4 con ci mang mc bnh. - Nam v n u c kh nng mc bnh nh nhau. - Hn nhn gia nhng ngi c quan h h hng c gp nhiu trong ph h ca loi bnh di truyn ny. Nhiu bnh di truyn gen tri tht ra c biu hin nhng ngi ng hp t nng hn so vi nhng ngi d hp t. V d: bnh lon sn sn bm sinh (achondroplasia) l bnh di truyn gen tri trn NST thng vi biu hin ln. Nhng ngi d hp t gn nh c mt cuc sng bnh thng vi tui th trung bnh t hn ngi bnh thng
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khong 10 nm. Tuy nhin nhng ngi ng hp c biu hin nng hn v thng cht tui thiu nin do suy h hp. C th phn bit bnh di truyn gen tri v gen ln da trn biu hin lm sng ca ngi d hp t: bnh di truyn tri c biu hin trn lm sng, trong khi bnh di truyn ln lun lun bnh thng trn lm sng. Mt im cn lu l thut ng tri v ln trong cch ni c dng ch kiu di truyn ch khng phi ni v gen. Xt trng hp bnh hng cu hnh lim, ngi ng hp t t bin ny c biu hin bnh, ngi d hp t bnh thng v mt lm sng nhng c nguy c b nhi mu lch rt cao. R rng l bnh hng cu hnh lim c c im ca mt bnh di truyn gen ln nhng c im ca ngi d hp lm bnh ny c tnh cht ca mt bnh di truyn tri. 4. Cc quy lut chung ca tnh di truyn Cc quy lut di truyn Mendel gi l cc quy lut truyn t tnh trng t th h ny sang th h khc. T ngi ta rt ra c cc quy lut ca tnh di truyn cho cc sinh vt nhn thc bc cao: - Tnh di truyn c tnh gin on do nhng nguyn t ring bit m bo (cc gen). - Mi tnh trng c xc nh bi cc nhn t di truyn ring bit l cc gen gen. cc gen ny truyn cho th h sau qua t bo sinh dc - Cc gen c duy tr dng thun khit qua nhiu th h, khng b bin i v cng khng b mt i. - C hai gii u tham gia nh nhau vo vic truyn t cc du hiu di truyn. - Cc gen c cp trong t bo c th, n c trong t bo sinh dc. cc con lai mt c ngun gc t b, mt c ngun gc t m, c th l tri hoc ln. Vic tm ra cc quy lut Mendel khng nhng c ngha l thuyt m c nhiu ng dng trong vic lai to ging.
Cu hi n tp
1. c im ca phng php th nghim ca Mendel l g?
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2. Mi quan h gia nguyn phn, gim phn v quy lut phn ly c lp ca Mendel. 3. Nu th nghim chng minh trc tip s phn ly mc giao t. 4. ngha ca s phn ly mc giao t. 5. Khi c hin tng tri khng hon ton v di truyn tng ng th t l phn ly kiu gen v kiu hnh nh th no?
Ti liu tham kho

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. 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.
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Chng 5
Tai lieu chia se tai: wWw.SinhHoc.edu.vn Tng tac gen
Mc tiu ca chng
Gii thiu v tng tac gen allele, tng tac gia cac gene khng allele, nhng phc tap trong biu hin gen va tac ng cua mi trng n s hinh thanh kiu hinh.
S tit: 3 Ni dung I. S tng tc gen gia cc gen alen

1. Hin tng gy cht S tng tc gia cc alen trong trng hp lai mt tnh l trng hp gen gy cht. y l trng hp lm bin i t l theo nh lut Mendel n gin nht. Vi du: chut , Ay: lng vng (tri) a: en hoc scla (ln) Khi ngi ta lai chut vng vng F1: thu c hai loi chut: 2 lng vng : 1 lng khc (s c la), ng thi trong cc la chut ra th s con ca n t hn 1/4 so vi cc t hp lai khc. Cc nhn xt ny c a n gi thit l chut lng vng c kiu gen d hp t Aya khi chng lai vi nhau lm xut hin chut AyAy khng c sc sng v chng b cht giai on sm ca phi. Ngi ta lm th nghim gii phu chut ci lng vng ang mang thai trong t hp lai gia lng vng vng u xc nh hin tng trn. l trong d con ca chut m c mt s bo thai lng vng khng pht trin v mt s b phn trong c th mang c im d hnh. Nh th chut ng hp t AyAy khng c sc sng do alen Ay l alen gy cht khng cho ng hp t sng c. Tc ng ca alen Ay v mu lng l tri so vi alen a v c th d hp t Aya c mu lng vng. Nhng v mt sc sng th
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Ay li ln so vi a v t hp Aya vn sng bnh thng do alen a ln t s gy cht ca Ay. y l v d v gen c tc ng ny tri nhng tc ng kia l ln so vi alen tng ng.
Hnh 5.1 Hin tng gen gy cht chut
Hinh 5.2 Kt qua phep lai gia cac chut di hp t lng vang. Khng phai tt ca cac chut th h sau u sng sot
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Hnh 5.3 S tng tc gia cc alen ca cng mt gen chut lang

agouti (1 allen dng hoang di v nhiu allen t bin) a. Chut lng en, bng vng (trn - tri), bng en (trn - phi) v chut lang agouti (di). b. Kiu gen v kiu hnh tng ng ca cc allele ca gen agouti. c. Lai gia cc dng thun to ra mt dy c th c 3 allele theo mt th t tri. Cho cc c th F1 giao phi vi nhau cho ra th h F2 c t l kiu hnh l 3:1. iu ny cho thy A, at v a l cc allele khc nhau ca cng mt gen
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Tai lieu chia se tai: wWw.SinhHoc.edu.vn Trng hp ny cn gp mt s i tng khc nh c chp

Khi lai c chp knh vi nhau F1 : 1/4 AA cht : 2/4 Aa : 1/4 aa : 2 chp knh : 1 chp vy
ngi bnh thiu mu hng cu lim do t bin: Ngi c kiu gen SS: thiu mu nng cht trc khi trng thnh. SA: sc khe bnh thng nhng i khi c triu chng thiu mu nh.
Hnh 5.4 Bnh hng cu li lim ngi
2. S tng tc gia cc alen ca cng mt gen Gia cc alen ca cng mt gen c mi quan h tri v ln. Trong mi tng tc gen ny ngi ta pht hin ra hin tng mt gen c nhiu hn 2 alen. V d: - S di truyn nhm mu A,B,O do 3 alen IA, IB, Io. Nhm mu ca i gia sc c hn 100 alen. - S di truyn mu mt rui gim do 1 gen gm 1 dy 12 alen quy nh, alen cui cng mt trng (w) v tnh tri gim dn theo hng sau:
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W+ > Wsat > Wco > WW > Wap3 > Wch > We > Wbl > Wap > Wi > Wt > W Tng ng: di - satsuma - san h (coral) - ru nho (wine) tri o (apricot) - cheri - son (eosin) - mu (blood) - tri o (apricot) - ng voi (ivory) - trng c (tinged) - trng (white) S biu hin tnh trng mu mt do s tng tc gia hai alen vi nhau: W+Wbl: hoang di WcoWbl: san h - Dy alen trong vic xc nh nhm mu ngi Cc alen lm xut hin nhiu nhm mu c trng ngi, lin quan vi c im khng nguyn ca th mu, quy nh s xut hin khng th c hiu trong huyt thanh mu. S pht hin ra nhm mu l do Landsteiner, ng thy trong mt s trng hp nht nh, khi truyn hng cu ngi ny vo huyt thanh ngi khc c hin tng ngng kt cc th mu. Khi truyn mu, hin tng ny c th gy cht. Ngi ta xc nh trong hng cu c 2 khng nguyn A v B, cn trong huyt thanh c 2 khng th lm ngng kt chng. Qun th ngi c phn ra theo c tnh ca mu thnh 4 nhm: nhm A c khng nguyn A v khng th khng B, nhm B c khng nguyn B v khng th khng A, nhm AB c c 2 khng nguyn khng c khng th, nhm O khng c khng nguyn v c c 2 khng th. Phn ng ca 4 nhm mu vi huyt thanh c khng th khng B v khng th khng A nh sau: hng cu nhm mu AB ngng kt vi huyt thanh c khng th khng B v khng th khng A. Hng cu nhm A ch b ngng kt bi huyt thanh nhm B. hng cu nhm B ch b ngng kt bi huyt thanh nhm mu A. Hng cu nhm O khng b ngng kt trong c 2 trng hp. Phn tch qu trnh di truyn cc nhm mu ngi chng minh rng 4 nhm mu c quy nh do s di truyn ca 3 alen (I A, IB, Io). Nhm mu AB l th d hp c kiu gen IAIB, nhm A: IAIA, IAIO, nhm B: IBIB, IBIO, nhm O: IOIO.
II. S tng tc gia cc gen khng alen

1. Tng tc t ch - T l 13:3
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Tai lieu chia CCIItai: ccii u xc nh mu lng trng. Mu se v wWw.SinhHoc.edu.vn g 2 kiu gen
trng kiu gen CCII l do gen C to mu b gen I t i, cn kiu gen ccii cho kiu hnh trng l do gen to mu trng thi ng hp ln P: g trng CCII F1 F2 ccii CcIi (g trng) 9 C-I- : 3 C-ii : 3ccI- : 1 ccii g trng
13 trng: 3 mu - T l 12:3:1 Alen tri A km hm s biu hin ca B locus khc. B ch biu hin aa. Aabb c kiu hnh khc Thi nghim: Lai bi qua mau xanh co kiu gen AABB vi bi qua trng co kiu gen aabb thi bi F1 AaBb co mau trng. Lai F1 vi nhau cho F2 t l 12 trng : 3 vang : 1 xanh P Bi qua trng F1: F2: Bi qua trng AaBb (qua trng) 9 A-B- : 3A-bb : 3 aaB- : 1 aabb 12 qua trng : 3 qua vang : 1 qua xanh
Hnh 5.5 Tng tc t ch c ch tri tao ra ty l kiu hinh 12:3:1 (a) va ty l 13:3 (b)
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Tai l 9 : 3chia se tai: wWw.SinhHoc.edu.vn lieu : 4 - T

Kiu gen aa cn tr s biu hin ca cc alen locus B, gi l t ch ln i vi locus B Th nghim: P: F1: F2: Chut en AAbb Chut trng aaBB AaBb (xm nu) 9 A-B- : 3 A-bb : 3 aaB : 1aabb 9 xm nu : 3 en : 4 trng
Hinh 5.6 Tng tac at ch do ng hp t gen ln
2. Tng tc b sung - T l 9 : 3 : 3 : 1 V d s di truyn hnh dng mo g P: g mo hoa hng AAbb ht u aaBB
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Tai lieu chia se(mo qu c ch) tai: wWw.SinhHoc.edu.vn F: AaBb

1
F2:
9 A-B- : 3 A-bb : 3 aaB- : 1 aabb
9 mo qu c ch : 3 hoa hng : 3 ht u : 1 mo n
Hnh 5.7 Hnh dng mo g
- T l 9 : 6 : 1 b , 2 cp alen xc nh hnh dng qu: trn, dt v di P: trn AAbb F1 aaBB AaBb (dt) trn
F2 9 A-B- : 3 A-bb : 3 aaB- : 1 aabb 9 dt : 6 trn : 1 di
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Hinh 5.8 S hinh thanh cac dang qua bi
- T l 9 : 7
Hnh 5.9 S hnh thnh mu hoa u thm Lathyrus odoratus
Th nghim u thm Lathyrus odoratus A-B-: hoa
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A-bb, aaB- : hoa trng P AAbb F1: F2: 9 3. Tng tc a gen

u thm hoa trng hoa trng aaBB AaBb (hoa ) 9 A-B- : 3A-bb : 3 aaB- : 1aabb : 7 trng
a. Tng tc cng gp Cc tnh trng chu s chi phi ca nhiu gen c gi l s di truyn a gen. Mi gen u c kiu hnh mc nht nh, nhiu gen n ny c tc dng cng gp theo mt hng. Cc c th c biu hin kiu hnh dao ng khc nhau do nhn nhiu hay t gen, c th xp chng theo mc biu hin thnh mt dy lin tc gi l s lng. Tnh trng do nhiu gen xc nh, nn biu hin kiu hnh ca chng d b bin i do tc ng ca mi trng. b. T l phn ly F2 Nm 1908 nh di truyn hc Thy in Nilson - Ehler khi nghin cu la m: Th h F1 A1a1A2a2 c mu hng do mang 2 alen tri A1 v A2, F2: A1A1A2A2 -----------> m a1a1a2a2 trng
F2 gia mu m v mu trng c cc mc mu trung gian: (3A), hng (2A) v hng (A) Chiu di tri bp v mu lng xm chut cng l nhng v d v s di truyn a gen. ngi nhiu tnh trng c s di truyn s lng nh tnh trng mu da, chiu cao... S di truyn mu da c th lin quan n 3 cp gen, gia dng en sm A1A1A2A2A3A3 v dng trng a1a1a2a2a3a3 c cc mu da en trung gian. T l phn ly gia da mu v da trng l 63 : 1.
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4. Tnh a hiu ca gen:
Ngay t thi Mendel, ng nhn thy 1 gen c th tc ng n nhiu tnh trng. V d: u H lan, gen nh hng n mu hoa ng thi nh hng c mu v ht, nh hoa ht xm, cn hoa trng ht trng. Hin tng 1 gen nh hng n nhiu tnh trng gi l tnh a hiu ca gen. Hi chng Marfan: bnh di truyn gen tri trn NST thng vi biu hin mt, xng v h tim mch. Gen gy ra hi chng Marfan trn nhnh di ca NST 15, m ha cho fibrilin (thnh phn m lin kt). Bnh xut pht t tnh trng t chc m lin kt b ko dn khng bnh thng gy nhiu hu qu khc nhau. Ngi bnh c tay chn di, khun mt hp. ngi, sai hng gen ca bnh thiu mu hng cu hnh lim gy ra hng lot chng bnh khc. Khong 25% cc bnh di truyn sai hng cu trc tim bm sinh c th dn n bin dng c xng (9%), h thn kinh trung ng bt thng (4%), sai hng ng tit niu hay thn (5%) v tiu ha (4%). Thc t bt k gen no cng c tnh a hiu v mt gen khng t th nhiu u c nh hng n gen khc. Nhng gen c hot ng sm trong qu trnh pht trin c th s c tc ng nhiu hn v lu hn.
III. Nhng phc tp trong biu hin cu gen

1. Gen bin i (Modifier gene) cc gen xc nh c tnh trng hay khng c tnh trng c gi l cc gen cn bn hay gen nn. Gen bin i l nhng gen khng c biu hin kiu hnh ring ca n nhng li c nh hng n s biu hin kiu hnh ca nhng gen cn bn khc. V d: b, lng u do gen tri S, c m do gen ln s quy nh. B c m hay khng c m l do cc gen cn bn xc nh. Nhng b c m, m t hay nhiu l do tc ng ca cc gen bin i. S m lng ch cng c s biu hin tng t: m nhiu hay t l do tc ng ca gen bin i.
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Hinh 5.10 Biu hin cua gen bin i trong hinh thanh 10 loai cho m
2. Cc tnh trng b gii hn bi gii tnh C nhng tnh trng m gen ca chng ch biu hin mt gii c gi l gen b gii hn bi gii tnh. i gia sc c sng s lng sa v lng m trong sa c biu hin ging ci. Cc con b c mang cc gen xc nh lng sa v m trong sa khng c biu hin nhng cc gen ny c truyn cho b ci con. Do trong chn ging b sa phi tuyn cc b c mang cc gen to sa tt em lai. g trng cng vy, chng mang cc gen trng nhiu hay t, ln hay nh nhng khng c biu hin. 3. Cc tnh trng c s biu hin ph thuc vo gii tnh C nhng tnh trng m s biu hin tri hay ln phu thuc vao gii tnh.
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V d: i gia sc c sng, gen c sng: H
Tai lieu chia se tai: wWw.SinhHoc.edu.vn h Gen khng sng:
Kiu gen HH to sng c con c ln con ci, kiu gen hh khng c sng c 2 gii. Kiu gen d hp t Hh nu con c s c sng (H l tri), nu con ci li khng c sng (H ln). d, tnh trng c ru xm hay khng cng thuc loi c biu hin ph thuc gii tnh, con c d hp t c ru xm, d ci d hp t khng ru. ngi hi u do gen B (ballness) xc nh. Kiu gen Bb c biu hin tri n ng, nhng biu hin ln n. iu ny gii thch v sao t c ph n hi u.
Hinh 5.11 Tinh hoi u co s biu hin phu thuc vao gii tinh
Ngn tay p t ca bn tay ngi c th di hn hay ngn hn ngn tr. Ngi ta cho rng s gim chiu di ngn tr do mt gen tri nam v ln n.
IV thm (penetrance) v biu hin (expression)

1. thm ( thm nhp) thm l khi nim ch mc tham gia ca alen vo kiu hnh.
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Taid: ngi c Kiu tai: IwWw.SinhHoc.edu.vn thm lieu chia se gen I c nhm mu A th I c V
A o A
100%, cn IO th 0% v khng thm nhp vo kiu hnh. Trng hp ngi c nhm mu AB th c IA ln IB u c thm 100%. Nhiu gen c thm khc nhau ty la tui. Nhng ngi mang gen epiloia (bnh di truyn) c ngi cht sm, c ngi sng v c th sinh con. Cc gen khng thm vn c th truyn cho i sau nh cc gen c thm hon ton. V d: Bnh Alzheimer lm ri lon tr nh, mt nh hng khng gian v thi gian, c biu hin ngi gi sau 60 tui. Hin nay xc nh c bnh do mt gen tri trn NST th 14 cua ngi.. y la trng hp c bit cho thy mt gen cua ngi co thm sau 60 nm hoc lu hn. Nhiu nhn vt ni ting mc bnh Alzheimer nh cu tng thng M R. Reagan. Bnh Huntington l bnh gy ra do ri lon thn kinh vi biu hin mt tr (dementia) v gia tng cc vn ng khng kim sot c ca cc chi dn n hin tng ma vn (chorea) nn i khi bnh cn c gi l bnh ma vn Huntington. Triu chng ca bnh thng khng biu hin trc 30 tui. T l thm thng c nh gi da trn vic xem xt mt s lng ln gia nh v xc nh t l ngi bt buc mang gen v nhng ngi ng hp t v gen bnh co biu hin bnh. Khi t l nhng ngi ny t hn 100% ta ni l c tnh thm gim hay tnh thm khng hon ton (incomplate penetrance). 2. hin hay biu hin biu hin c dng ch mc nhiu t ca tnh trng khi thm hon ton. V d: s cm nhn v ng ca cht phenylthiocarbamide (PTC) hay khng cm nhn ngi do 1 gen xc nh. Tuy nhin nhng ngi cm nhn v ng c hin khc nhau: c ngi cm nhn v ng nng 1.300 mg/l hoc cao hn, trong khi c bit c nhng ngi cm nhn v ng nng rt thp l 0,16 mg/l, nhiu ngi khc cm nhn v ng cc nng trung gian.
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Tai lieu trng se tai: hin n nh sut di nh nhm mu, chia ngi c wWw.SinhHoc.edu.vn Nhiu tnh
mu mt... - Biu hin a dng (Variable Expression) Mt tnh trng phc tp khc l s biu hin a dng ca bnh. Bnh c th c tnh thm hon ton nhng mc nghim trng ca bnh c s thay i rt ln. V d: Bnh u x thn kinh (neurofibromatosis) type I (cn gi l bnh Von Recklinghausen). B hoc m c th c bnh rt nh, nh n ni h khng ngh l mnh mc bnh. Nhng h c th truyn gen bnh cho con v i khi chng c biu hin bnh rt nng. Biu hin ca bnh l bnh nhn c cc chm c ph - sa trn bng v cc u x thn kinh b hay cc u x thn kinh pha lng. C 2 khi nim thm v biu hin c nh di truyn hc ngi Nga Timofeev - Resopski nu ra vo nm 1925 nh gi mc th hin ra kiu hnh ca cc gen. Ngoi ra, s biu hin ca kiu gen ra kiu hnh cn ph thuc vo mc phn ng.
V. Tc ng ca mi trng
Kiu gen cn chu nhiu tc ng khc nhau ca mi trng bn trong v ngoi c th 1. Tc ng ca mi trng bn ngoi a. Nhit Tc ng cn bn ca nhiu gen ch yu l kim sot tc phn ng sinh ha thng qua enzyme l nhng cht c cc gen xc nh v mt di truyn. Gia nhit v tc phn ng c s lin quan cht ch. Nhit nh hng n s biu hin kiu hnh trong nhiu trng hp. V d: s biu hin tnh trng lng en chp mi, tai v chn ca ging th Himalaya nhit thp khi pht trin b lng. Nhit c th nh hng n thm v hin. b. Dinh dng
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Tai lieu chia se hp ch dinh dng nh hng n biu tai: wWw.SinhHoc.edu.vn Trong mt s trng
hin kiu hnh. V d s biu hin m vng ca th do 2 yu t: s hin din ca gen ng hp t ln yy v lng thc vt xanh (xanthophyll) trong thc n. Nu thiu thc vt xanh trong thc n, m vng khng xut hin. Bnh phenylketonuria (PKU) c gp ngi da trng vi t l 1/10.000 ln sinh. Cc t bin locus m ha cho enzyme chuyn ha phenylalanine hydroxylase lm cho ngi mang kiu gen ng hp khng th chuyn ha amino acid phenylalanine. Trong khi nhng tr s sinh mc bnh phenylketon niu c biu hin bnh thng sau sinh th s khim khuyt chuyn ha s lm tch ly dn phenylalanine v cc sn phm chuyn ha c khc dn n tn thng h thn kinh trung ng v gy ra biu hin chm pht trin tr tu trm trng. Nh vy kiu gen PKU s gy ra kiu hnh bnh l nghim trng. Tuy nhin nu tr mang kiu gen bnh c pht hin sm qua sng lc trc sinh, biu hin ca bnh c th trnh bng ch n ngho phenylalanine. Nh vy, mc du tr mang kiu gen PKU nhng nh ch n ph hp trnh c tnh trng chm tr. c. nh hng ca c th m Sau khi trng c th tinh, c th m c th nh hng n s pht trin. V d mu ngi m c kiu gen rh- (nhn t rhesus m), nu a con th nht c Rh+ sinh ra s khng sao, nhng a con th hai c th b cht. 2. Tc ng ca mi trng bn trong Qu trnh pht trin c th tri qua nhiu bc trung gian phc tp. Ngay trong c th c nhiu tc ng gia cc cu trc khc nhau v vi kiu gen nh cc tng tc: gen vi gen, gen vi NST, NST - nhn, nhn - t bo cht, t bo - m... y ch nu vi tc ng c tnh cht chung tng qut: a. Tui Nhiu tnh trng v bnh di truyn ngi c biu hin trong mt tui nht nh. Bnh alcaptonuria (nc tiu c acid homogentisic b en khi c O2) biu hin ngay lc mi sinh ra. Bnh vy c biu hin trong 4 thng u. Bnh tiu ng v chng co git Huntington biu hin nhiu tui khc nhau. Bnh Alzheimer biu hin sau 60 tui. b. Gii tnh
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Tai lieu chia se tai: wWw.SinhHoc.edu.vn hn Gii tnh c nhiu nh hng n s biu hin ca gen nh gii
s biu hin hay tnh tri ln ph thuc vo gii tnh. Ngoi ra c nhng gen lin kt vi gii tnh. C th hormone sinh dc tc ng n biu hin ca cc gen. Nh vy mi trng bn trong v ngoi c th c nhiu nh hng phc tp khc nhau ln s biu hin kiu hnh ca cc gen. Nhiu bnh ngi nh tim mch, huyt p... trc y khng coi l cc bnh di truyn. Quan im mi hin nay cho rng l nhng bnh di truyn m biu hin ph thuc mi trng. Trn thc t cc gen lin quan n bnh ny c truyn th trong cc gia nh c bnh.
Cu hi n tp
1. Phn bit gen alen v gen khng alen 2. Nu s khc nhau gia t ch gen tri v t ch gen ln 3. Xc nh bn cht di truyn ca s xc nh cc dng mo g. 4.. Khi nghin cu hin tng di truyn, cc nh di truyn hc pht hin t l 9 : 6 : 1 trong th h con. Hy gii thch kt qu di truyn ny. C th kim tra gi thuyt ny nh th no. 5. Phn bit a gen v a hiu ca gen.
Ti liu tham kho

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. 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.
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Stansfield W.D. 1991. Schaums outline of theory and problems of genetics. McGraw-Hill, Inc., New York.
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Chng 6
Tai lieu chia se tai: wWw.SinhHoc.edu.vn Hc thuyt di truyn nhim sc th
Mc tiu ca chng
Gii thiu s di truyn lin kt vi gii tnh, mt s v d v cc gen lin kt vi nhim sc th gii tnh v ng dng ca chng. Cc gen trn cng mt nhim sc th di truyn cng nhau theo quy lut lin kt.
S tit: 5 Ni dung I. S xc nh gii tnh v s di truyn lin kt vi gii tnh

1. T l phn li gii tnh Quan st nhiu loi sinh vt chng ta thy c hin tng c ci. Nhiu s liu cho thy t l gii tnh l 1 : 1. T l ny trng vi t l phn li n tnh khi lai phn tch Aa aa hoc Aa AA. Nh vy gii tnh c s phn ly nh mt du hiu Mendel. S phn li ny cho thy mt gii tnh ng hp t, cn gii tnh kia di hp t. Vic pht hin ra cc nhim sc th gii tnh X v Y cho thy b nhim sc th ca c th c v ci ch khc nhau mt cp nhim sc th gii tnh, cn cc nhim sc th thng u ging nhau. V d b nhim sc th nhim sc th ca rui gim c 8 nhim sc th : rui ci: 6A + XX v rui c: 6A + XY S kt hp gia c v ci dn n t l phn chia 1 ci : 1 c. Tuy nhin t l ny cn ph thuc vo la tui. Thc t ngi, trong mi gia nh t l c dao ng, t l trn ng khi thng k vi s lng ln. 2. Cc gen lin kt vi gii tnh Cc gen nm trn nhim sc th gii tnh s c s di truyn khc hn so vi cc gen nm trn nhim sc th thng. Thc t cho thy nhim sc th Y hu nh khng cha gen.
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2.1. Lai thun nghch: P: G: F1: G: F2: ci mt X X XW XWXw XW , Xw

W W

- Ly rui ci mt lai vi rui c mt trng: c mt trng XwY Xw , Y XWY XW , Y
XW XW : XW X w : XW Y : Xw Y
Kiu hnh: 3 : 1 trng (c) T l phn li trong trng hp ny khng khc lm so vi quy lut Mendel - Ly rui ci mt trng lai vi rui c mt : P: G: F1: G: F2: ci mt trng XwXw Xw XWXw XW , Xw XW Xw : Xw X w : c mt XWY XW , Y XwY Xw , Y XW Y : Xw Y
1 m : 1 mtrng : 1 m : 1 mtrng th h th nht c s di truyn cho, t l phn li F2 l 1: 1: 1: 1 Nh vy i vi cc gen nm trn nhim sc th gii tnh chn c hay ci mang du hiu no lai l c ngha
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Hnh 6.1 Lai thun nghch rui dm mt vi rui mt trng
3. Cc tnh trng lin kt vi gii tnh trong di truyn hc ngi - Cc gen lin kt vi nhim sc th gii tnh X Mt s bnh di truyn ngi nh bnh mu khng ng hay m mu u l cc tnh trng do cc gen lin kt vi nhim sc th gii tnh. S di truyn cho th hin r: ng ngoi b bnh truyn gen mm bnh cho m, m truyn bnh cho con trai. Cho n nay c t nht 50 bnh v 200 du hiu di truyn gn vi nhim sc th X ca ngi c bit.
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Tai lieu chia se v Y c nhng phn tng ng chung. Trong tai: wWw.SinhHoc.edu.vn - Cc nhim sc th X
nhng phn ny cha cc gen xc nh nhng tnh trng di truyn theo cch nh nhau c nam v n, nh: + Bnh da kh sc t: Bnh nhn siu nhy cm vi tia cc tm, di nh hng ca cc tia ny trn phn h ca c th xut hin nhng vt sc t thot u dng tn nhang, v sau cc dng u nh ln hn (nt rui) v cui cng l cc u. i vi 2/3 s ngi mc bnh th bnh da kh sc t kt thc nguy him vo lc bc vo thi k chn sinh dc. + Hi chng Oguti: mt bnh hay gp Nht, biu hin vim mng li sc t mt v pht trin d hnh vng mc. * Phn khng tng ng ca nhim sc th Y c gen xc nh nam tnh v mt s hi chng: + Mng gia ngn
Hnh 6.2 Tt mng gia ngn
+ Tai rm lng
Hnh 6.3 Tnh trng mc lng vnh tai n ng
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Tai lieu chia se tai: wWw.SinhHoc.edu.vn * Phn khng tng ng ca X c cc hi chng:

+ Bnh mu kh ng (hemophilia): bnh c th c pht trin do kt qu khng cht globulin chng chy mu. Bnh mu kh ng c m t trong ph h cc gia nh hong tc chu u l mt trng hp in hnh, bt u t n hong Victoria, sau ny gp cc hong t Ty Ban Nha, c, Nga. + Bnh khng c gamma-globulin lm gim st r rt sc khng i vi cc bnh truyn nhim khc nhau. + Bnh i tho nht: ngi bnh b gim chc nng ca tuyn yn, dn n c th b mt nc r rt. Tr em mc bnh ny sinh trng chm, ri lon tm thn, suy nhc c th i khi cht. + Bnh m mu: ri lon v kh nng nhn mu sc. Hin tng ri lon th gic ny da trn c s tc ng ca nhiu gen. Hin tng m v mu xanh gi l chng m mu . + Bnh lon dng c Duchenne: bnh do gen ln lin kt vi nhim sc th gii tnh X. Bnh xut hin t lc cn t tui, dn dn dn n tn ph v cht tui di 20. Do n ng b lon dng c Duchenne khng c con, cn ph n d hp v gen ny li hon ton bnh thng * Cc bnh di truyn do gen tri lin kt vi nhim sc th X c s lng t hn v c ngha v mt lm sng khng bng trng hp di truyn gen ln trn nhim sc th X, ngoi tr trng hp hi chng nhim sc th X d gy. Mt s bnh di truyn do gen tri lin kt vi nhim sc th X: + Bnh ci xng do gim phosphat mu l bnh m thn b suy gim kh nng ti hp thu phosphat, dn n vic ct ha bt thng lm xng b cong v b bin dng. y l bnh di truyn gen tri lin kt nhim sc th X nn ngi n c kh nng mc bnh cao hn ngi nam. + Hi chng nhim sc th X d gy: l hi chng di truyn kiu tri lin kt nhim sc th X, th hin s chm tr ca ngi bnh. Hi chng c gp vi t l 1/4.000 nam v 1/8.000 n. ngi n, mc chm tr c xu hng nh hn v thay i mc biu hin nhiu hn ngi nam.
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4. Gen nam gii v gen n gii ngi 4.1. Gen xc nh nam gii
Gen nam tnh SRY (Sex determining region Y) c pht hin vo nm 1990 trong mt s trng hp ngoi l khng tun theo nguyn tc XX l n v XY l nam. tm thy ngi nam bnh thng c XX (nhng bt th) c SRY trn mt trong 2 nhim sc th X v ngi n bnh thng mang XY nhng mt SRY trn nhim sc th Y.
Hnh 6.4 S phn ha di truyn cc on ca X v Y
Gen SRY cn gi l nhn t xc nh tinh hon TDF (Testis determining factor) nm trn mt on ca vai ngn ca nhim sc th Y ngi. C gi thuyt cho rng gen ny sn sinh ra protein gn ADN hot ha mt hay nhiu gen khc trong h thng cc nhn t hot ha cc gen iu khin s pht trin ca tinh hon. Khi thiu s hin din ca TDF m sinh dc s pht trin thnh non hong. TDF c tnh bo tn cc ng vt c v, chng c nhiu im ging nhau gia cc loi. 4.2. Gen xc nh n gii Gen xc nh n gii DSS (Dosage sensitive sex reversal) c pht hin vo nm 1994 do G. Carmerino (). nhng ngi nam (XY) nhng c c quan sinh dc n c gen SRY trn nhim sc th Y, c trng bi s lp li 1 on vai ngn nhim sc th X. S bt thng ny rt him
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(khong 1/20.000 ngi). S c nhim sc th ny khng lin quan n gim phn. Nhng ngi mang gen ny bt th. Trong s 8 ngi bnh nghin cu, 3 ngi c Y bnh thng v mt c X vi vai ngn gp i, cn 5 ngi c mt X nguyn trng v mt Y c vai ngn ca X ghp thm vo. Trong 2 trng hp c s hin din ca 2 on vai ngn ca X. Cc nghin cu tip cho thy on vai ngn ca X gn vo cng di, gii tnh cng lch v to phi n. Gen DSS c tch ra. 5. Nhim sc th X bt hot ngi Trong phi ngi, mt nhim sc th X bt ngun t m hay cha trong mi t bo soma s bt hot ngu nhin. Tt c th h t bo con u c truyn nhim sc th X bt hot. Thng th nhim sc th X c cu trc khng bnh thng bt hot, tr mt s ngoi l lin quan n cc t bin lin kt gii tnh. Khi nhum mu nhn t bo ca ngi n, nhim sc th X bt hot th hin dng trn, c gi l th Barr. Trung tm bt hot nm vai di q, gn tm ng. 6.V d ng dng s di truyn cc gen lin kt vi gii tnh - g: B: lng vn, b: lng trng, nm trn X. P: G: F1: lng vn lng trng ZBY ZB, Y ZBZb lng vn : : Zb ZbY lng trng ZbZb
ng dng vo nng nghip, gip phn n ngay khi lc g mi n: mun nui ly trng, chn g mi; mun pht trin sn lng, nui g trng
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Hnh 6.5 ng dng ca di truyn lin kt vi nhim sc th gii tnh trong phn an g
- tm: L: mu sm, l: mu sng P: F1 ci ZLW mu sm ZLZl mu sm : x c ZlZl mu sng ZlW mu sng
Hnh 6.6 ng dng di truyn lin kt vi nhim sc th gii tnh trong phn loi trng tm
Tm c cho nhiu t hn tm ci: 20-30%. Da vo tnh cht lin kt vi gii tnh ngi ta c th phn bit c 2 loi tm c v ci ngay
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t giai on trng da vo mu sc trng: trng mu sng pht trin thnh tm ci, trng mu sm pht trin thnh tm c. ngha: Da vo cc du hiu c th phn bit gii tnh ng vt ngay t khi sinh vt cn b. Trong cng tc chn ging gia sc th vn phn bit gii tnh ngay t u c th phn vng hp l cho vic chn nui. Mt s thc vt c hin tng di truyn lin kt vi gii tnh : ch l. 6. Hin tng khng chia ly ca nhim sc th th nghim: rui ci mt trng x c mt F1 thu c ci mt , c mt trng Calvin Bridges pht hin trng hp ngoi l trong kt qu lai gia rui ci mt trng vi rui c mt : trong 2000 rui F1 th xut hin 1 con ci mt trng v 1 con c mt . Quan st t bo hc cho thy rui ci c cp nhim sc th XX i cng nhau do khng chia ly (nondisjunction) trong gim phn nn rui ci c kiu gen XwXwY biu hin mt trng, rui c XWO c mt . P: G: F1 : XwXw Mt trng XwXw, O XWXwXw : XwXwY : XW, Y XWO : OY cht (thng cht) XWY Mt
Siu ci mt : ci mt trng : c :
T kt qu ny ca Bridges cho thy s xc nh gii tnh rui gim khng do nhim sc th Y m do t s X/A quyt nh Nu X /A = 0,5 tr xung : rui c. X/A = 1,0 tr ln : rui ci X/A = 0,5 - 1,0 : gii tnh trung gian
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Hinh 6.7 S hinh thanh th h sau do s khng phn ly cua cp nhim sc th gii tinh
Hinh 6.8 S khng phn ly cua nhim sc th (a) S khng phn ly nhim sc th con cai XX (b) S khng phn ly nhim sc th con cai XXY
Gii tnh ca rui gim
Cu trc nhim sc th
T l X/A
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Siu ci

AAXXX 1,5 1,0 1,0 1,0 1,0 0,67 0,5 0,33 + T bi + Tam bi + Lng bi + n bi AAAAXXXX AAAXXX AAXX AX AAAXX AAXY AAAXY
Rui ci bnh thng
Gii tnh trung gian c bnh thng Siu c
7. Xc nh gii tnh do s bi th cn trng b Hymenoptera (ong , kin): c (n), ci (2n), ong th (2n) Ong c c pht trin trinh sinh t trng khng c th tinh c b nhim sc th n bi (n). Trong kiu xc nh gii tnh ny khng c nhim sc th gii tnh. Cn gii tnh ci th xc nh do nhng alen gii tnh khc nhau phi hp, ong th v ong cha u l ong ci. S khc nhau gia ong th v ong cha l do ngay t nhng ngy u mi n, thc n ca ong th b thiu mt s vitamin nn bt th. Ong th lm nhim v bo v t. Ong c c pht trin t trng khng th tinh nn t bo sinh dc l n bi, c th phc hi li nhim sc th lng bi nn c kch thc v sc sng bnh thng. 8. Xc nh gii tnh do iu kin mi trng mt s loi, s xc nh gii tnh do iu kin mi trng quyt nh. loi bin Bonellia viridis, cc u trng xut hin sau khi c th tinh sng t do mt thi gian ri hoc bm xung y thnh con ci hoc bm vo con ci ri chiu vo t cung thnh con c v th tinh. C c v ci u c kiu gen nh nhau.
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Tai lieu chia se tai:yu t quyt nh gii tnh l trng lng wWw.SinhHoc.edu.vn cy Arisaema japonica,
c: nhng c to nht v cha nhiu cht dinh dng nht sinh ra cy c hoa ci, trong khi cc c gy ch cho cy c hoa c.
II. S di truyn lin kt

trong c th sinh vt, s lng gen rt nhiu nhng s lng nhim sc th li t nn nhiu gen cng nm trn nhim sc th. Khi 2 hay nhiu gen nm trn mt nhim sc th, chng s cng di truyn vi nhau gi l s di truyn lin kt. Cc gen lin kt c xu hng cng di chuyn vi nhau trong qu trnh hnh thnh giao t. 1. Hin tng lin kt Bateson v Punnet nm 1906 pht hin ra hin tng lin kt khi thc hin php lai u thm (Lathyrus odoratus) vi hai tnh trng: R : hoa thm Ro: ht phn di F1 : r : hoa ro: ht phn trn
P : hoa thm ht phn di hoa ht phn trn 100% hoa thm ht phn di. 182 , ht phn trn; 30 , ht phn di 23 thm, ht phn trn; F2 : 192 hoa thm ht phn di;
Hinh 6.9 Kiu hinh rui hoang dai va rui t bin
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2. Lin kt hon ton B : thn xm

b : thn en vg : cnh ct Vg : Cnh di
Th nghim : P : rui gim mnh xm cnh di rui gim thn en cnh ct BVg BVg G: F1 : Lai phn tch rui c F1 : BVg bvg c xm di G: FB : 50% xm di BVg bvg : 50 % en ct bvg BVg bvg bvg bvg bvg ci en ct bvg BVg BVg bvg (100% xm di) bvg bvg bvg
T l phn li 1:1 ging vi lai mt tnh, hai gen b v vg i cng nhau nh 1 gen. Mt hin tng cho n nay cha r c ch l rui gim c khng xy ra ti t hp di truyn, nn c s lin kt hon ton ca cc gen trn mt nhim sc th. 3. Hin tng di truyn lin kt khng hon ton Dng rui gim ci F1 ca th nghim trn lai phn tch: F1 : Thn xm, cnh di BVg bvg G: BVg bvg bVg Bvg bvg 100% 41,5% 41,5% 8,5% 8,5% thn en, cnh ct bvg bvg
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FB :
Tai lieu chia se bvg wWw.SinhHoc.edu.vn tai: BVg Bvg bVg

bvg bvg bvg bvg
41,5% xm di : 4,5% en ct : 8,5% xm ct : 8,5% en ct. Kt lun: c hin tng hon v gen gia gen quy nh thn xm cnh di vi gen quy nh thn en cnh ct trong qu trnh phn bo 4. Cc nhm lin kt (Gene linkage) Cc gen cng nm trn mt nhim sc th, cng di truyn vi nhau c xp vo mt nhm gi l nhm lin kt gen. S nhm lin kt gen ti a bng s cp nhim sc th. V d: Rui gim 2n = 8, s nhm lin kt gen ti a = 4 Bp : 2n =20, c 10 nhm lin kt gen
III. Hin tng ti t hp

1. Ti t hp v trao i cho Khi cc gen lin kt khng hon ton, xut hin cc dng giao t mi khng ging cha m do c s sp xp lai cc gen. Hin tng ny gi l ti t hp (recombination) v cc dng mi xut hin gi l dng ti t hp (recombinant). nh gi mc lin kt, dng khi nim tn s ti t hp. % ti t hp = S c th ti t hp / tng s c th 100% Nhiu th nghim cho thy tn s ti t hp gia 2 gen l mt s tng i n nh t ln lai ny qua ln lai khc, khng ph thuc vo cch sp xp. Hai alen tri cng mt pha trn nhim sc th gi l v tr cis(AB/ab), 2 alen tri nm trn 2 nhim sc th gi l v tr trans (Ab/aB). Hin tng ti t hp c c nh qu trnh trao i cho (crossing over). Trong 2 nhim sc th tng ng hon v nhau hay i cho nhau nhng im nht nh. Nhim sc th tng ng tip hp nhau v trao i cho xy ra gia cc chromatid khng ch em. Cc giao t t cc chromatid khng c trao i cho (kiu cha m) c gi l giao t kiu cha m. Cc giao t t 2 chromatid khc c xy ra trao i cho gi l giao t ti t hp.
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Hnh 6.10 Trao i cho gia cc chromatid
Hnh 6.11 S to thnh cc dng ti t hp
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2. C s t bo hc ca trao i cho
Nm 1931, cc th nghim chng minh c s t bo hc ca ti t hp di truyn do Stern tin hnh Drosophila melanogaster v do Creighton v Mc Clintok tin hnh ng. C 2 th nghim u dng "du chun" v hnh dng trn mt trn hai nhim sc th tng ng c th nhn thy c khi quan st t bo hc. Hai nhim sc th tng ng c phn bit vi nhau v hnh thi ny, mang cc alen tng ng khc nhau v mt di truyn ca mt s cp gen. Ti t hp di truyn s to ra cc kiu hnh c o km theo cc thay i t bo hc d quan st v d on c. Th nghim lai ng vi cc gen c biu hin r rng nm trn cp nhim sc th s 9 c du c bit nhim sc th c 1 u c g ln v phn sau di ra, nhim sc th kia ngn hn khng c g. Cc gen c s dng: C+ : c mu , c: khng mu W+ : bp t (tinh bt), w: bp np (h bt) Cho lai bp c mu, t vi bp khng mu , np. Kt qu thu c 4 dng: c mu, np; khng mu, t; c mu, t; khng mu, np.
Hinh 6.12 Trao i cheo nhim sc th s 9 cua bp c quan sat da trn "du chun"
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Tai vo ktchialai, i chiu vi cc quan st nhim sc th v mt lieu qu se tai: wWw.SinhHoc.edu.vn Da

hnh thi: thu c dng nhim sc th c g nhng ngn, cn dng kia khng g, di v 2 dng ging b m: c g, di v khng g, ngn. Chng t c xy ra trao i cho ca cc on nhim sc th. Stern dng nhim sc th X mt u mt c dnh mt on nhim sc th Y. Cc nhim sc th khc c di tng t, vi tm ng. Hai cp gen c dng l carnation (car: ln, mt nht) - hoang di (+, tri, mt ) v Bar (B: tri, mt hnh thi) v hoang di (+, mt bnh thng). Rui ci m d hp t c 2 gen, c kiu hnh mt dng thi (car B) vi rui c mt nht, dng thng (car +). Th h con nhn c c 4 loi kiu hnh tng ng vi cc du hiu hnh thi trn nhim sc th: ngoi 2 kiu c cha m cn c 2 kiu hnh ti t hp l mt nht, hnh thi (car B) v mt , dng thng (car++).
+
Hnh 6.9 S trao i cc on nhim sc th to cc dng ti t hp Hinh 6.13 Trao i cheo rui dm c quan sat da trn "du chun"
3. Trao i cho trong giai on 4 si
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Hnh 6.14 S trao i cho n v trao i cho kp
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Tai lieu chiagiai on 4wWw.SinhHoc.edu.vn ra sau se tai: cromatid, tc trao i cho xy Trao i cho
khi nhim sc th t nhn i (cn gi l giai on 4 si). V nguyn tc c th cho rng trao i cho c th xy ra c khi nhim sc th cha t nhn i (giai on 2 si) Phn tch b bn c th gii quyt vn ny. Phn tch b bn l php phn tch di truyn hc nghin cu bn sn phm trc tip ca gim phn khi t bo lng bi d hp v mt gen hay nhiu gen lin kt phn chia gim phn. Nm 1925, C. Bridge v I. Anderson chng minh trao i cho cc cromatid rui gim. Tc gi s dng dng rui c nhim sc th X mang thm on nhim sc th Y (X,XY) d hp v cc gen ca nhim sc th X: f (forked) - lng phn nhnh, g (garnet) - mt rc. Khi cho lai con ci ny vi con c bnh thng th chng truyn trc tip 2 nhim sc th X cho th h sau v ch mt na th h con ca chng sng st. Khi y mt phn c th con i sau t php lai ny l ng hp theo cc gen ca nhim sc th X. Cc th ng hp ny ch c th xut hin do trao i cho giai on 4 si trong on gen - tm ng. 4. Trao i cho nhiu ln Trao i cho gia 2 chromatid c th xy ra nhiu ln: 2, 3, 4 ln ... Nu 2 trao i cho xy ra trn cng 2 chromatid on gia 2 gen nh du th sn phm cui cng u c kiu cha m, nn khng pht hin c. Kiu trao i cho ny ch c th pht hin c khi s dng thm mt gen nh du th ba nm gia 2 gen ny. Nu xc sut trao i cho gia A v C v gia B v C tng ng vi x v y, th xc sut xy ra trao i cho i l: 0,2 0,1 = 0,02 (2%) 5. Nhiu (Interference) v trng hp (Coincidence) Thng th s trao i cho mt ch lm gim xc sut trao i cho th hai gn k n. l hin tng nhiu. nh gi kt qu ngi ta dng h s trng hp.
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Tai lieu chia sei cho i quan st c tai: wWw.SinhHoc.edu.vn % trao

H s trng hp = % trao i cho i theo l thuyt S trng hp + nhiu = 100% = 1 V d: Bit khong cch A-B = 10 n v (10%) v B-C = 20 n v (20%), nu khng c nhiu th tn s trao i cho i theo l thuyt l 0,1 0,2 = 0,02 hay 2%. Gi s quan st c tn s trao i cho i l 1,6%. S trng hp = 1,6/2,0 = 0,8. iu ny cho thy trao i cho i ch xy ra c 80% v s nhiu 1,0 - 0,8 = 0,2 (hay 20%)
IV. Xc nh v tr gen v bn di truyn

1.Xc nh vi tr gen Morgan cho rng nhng gen ng gn nhau th lin kt cht, cn cc gen ng xa nhau th lin kt yu. Nhng gen ng gn nhau lin kt cht nn t xy ra trao i cho, tn s ti t hp nh, cn cc gen ng xa nhau th mc lin kt yu nn tn s ti t hp ln hn. Nu cho rng cc phn ca nhim sc th c kh nng trao i cho nh nhau th tn s ti t hp phn nh khong cch tng i gia cc gen v t l nghch vi mc lin kt gen. S phn trm ti t hp c dng lm s o khong cch gia 2 gen trn bn di truyn. Mt n v bn c coi l n v o khong cch gia 2 cp gen khi trong 100 sn phm ca gim phn c mt dng ti t hp 1% ti t hp = 1 n v bn , n v ny c gi l centiMorgan (cM). Mi cM bng khong 1000 kb hay 106 bp. Nh vy bit c tn s ti t hp gia cc gen c th xc nh v tr ca chng trn nhim sc th. Mun xc nh v tr ca mt gen bt k phi tin hnh lai v qua 2 bc: - Cn c t l phn ly xc nh nhm lin kt gen - Da vo tn s ti t hp so vi 2 gen khc xp v tr trn nhim sc th. A B
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+ Nu:

AC + CB = AB CB - CA = AB CA - CB = AB
C nm gia AB: C nm ngoi pha A: C nm ngoi pha B:
So snh c th tn s ti t hp gia C-A, C-B, A-B xc nh c v tr ca C. 2. Bn di truyn ca nhim sc th v bn di truyn t bo Nh xc nh c v tr gen, bn di truyn nhim sc th ca nhiu i tng nh rui dm, c chua, bp,... c xy dng.
Hinh 6.15 Ban di truyn nhim sc s 12 cua ca chua
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Tai lieu chia se tai: wWw.SinhHoc.edu.vn c Nm 1943, nhim sc th khng l tuyn nc bt rui dm
pht hin. Quan st knh hin vi c th nhn thy cc vt nhum mu c trng (khong 5.000 vt ca nhim sc th khng l sau khi nhum. Nhiu dng t bin thng l t bin nhim sc th gy nn nhng bin i hnh thi quan st r rt trn nhim sc th khng l. iu ny c s dng lp bn di truyn t bo (cytogenetic map) m khng theo tn s ti t hp do lai. S i chiu gia bn di truyn nhim sc th v bn di truyn t bo cho thy c s ging nhau v trnh t sp xp gen theo ng thng, tuy khong cch c khc nhau (do hin tng nhiu). iu ny khng nh thm gen nm trn nhim sc th.
Hinh 6.16 Ban di truyn nhim sc s 10 cua bp
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Hinh 6.17 Th di hp mt oan nhim sc th cua rui dm c s dung lp ban di truyn
Hinh 6.18 Ban di truyn cua E.coli
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* c im chnh ca hc thuyt di truyn nhim sc th
- Cc gen nm trn nhim sc th sn xut theo ng thng to thnh cc nhm lin kt c s lng bng s cp nhim sc th - Cc gen cng nm trn mt nhim sc th c s di truyn lin kt v mc lin kt ph thuc vo khong cch gia cc gen - Gia cc nhim sc th tng ng c th xy ra trao i cho dn n ti t hp cc gen. Ti t hp l mt ngun bin d quan trng cung cp nguyn liu cho qu trnh chn lc t nhin v chn lc nhn to. - S lin kt cc gen v s ti t hp gia chng do trao i cho l nhng hin tng sinh hc trong biu hin s thng nht gia tnh bin d v tnh di truyn.
V. Nhim sc th ngi v bn nhim sc th ngi

1. Nhim sc th ngi Nm 1956, J. H. Tjio v A. Levan mi xc nh c chnh xc s lng nhim sc th ca ngi l: 2n = 46. Sau nh k thut nhum mu bng giemsa v quan st hin vi hunh quang mi pht hin cc vt c trng xy dng nn nhim sc . S dng mu lm tiu bn quan st nhim sc th: Nui cy t bo bch cu mu ngoi vi ca ngi bnh thng v ngi mc bnh c p dng trong khong nm gn y. Nhng phng php ny c ng dng rng ri nht sau khi pht hin c hp cht polysacchyrid-protid ly t ht c ve dng lm cht gy ngng kt khng c hiu hng cu. Ngi ta dng cht phytohemaglutinin ny cng vi dung dch nhc trng cho php thu c kt qu ca s phn chia t bo mu ngoi vi rt tt. Phng php ny c nhm nghin cu ca Moorhead sa i v p dng. C s ca phng php ny l ngi ta trn ln huyt thanh c ln bch cu vo mi trng dinh dng vi mt t l nht nh ri cho thm vo hn hp cht phytohemaglutinin, sau cho vo l trung tnh ri nui cy. Ngoi cht phytohemaglutinin chit t u c ve cn nhiu cht khc cng c tc dng ngng kt hng cu. Trong qu trnh nui cy bch cu cng c th tin hnh quan st s chuyn ha cc loi t bo bch cu. S phn chia t bo bch cu lm c s cho nghin cu c im t bo bch cu trong mu. Trn c s nghin cu
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t bo mu bnh thng v bnh l, c th pht hin ra trng thi bnh l ca t bo bch cu ngi v ng vt. 2. K thut lai t bo soma n gia nhng nm 1960 ch mi xc nh c mt cch ng tin cy 3 nhm lin kt (mi nhm c 2 gen) trn nhim sc th thng v 4 gen trn nhim sc th X ngi, theo thng k t cc ph h, nhng cha bit nhim sc th no. Vo nm 1967, Mc Weiss v H. Green s dng k thut lai t bo soma (somatic cell hybridisation) ln u tin xc nh c gen TK m ha cho enzyme thymidin kinase nm trn nhim sc th 17. Cc dng t bo soma ca ngi v cc ng vt c v, khi nui chung vi s hin din ca virus Sendai c th dung hp hay lai vi nhau. Cc t bo dung hp ny trong qu trnh phn bo tip theo s mt dn mt s nhim sc th ca t bo cha m. V d, t bo ngi dung hp vi t bo chut, khi cc t bo phn chia, cc nhim sc th ca ngi b mt nhanh. Sau khong 30 th h t bo, dng t bo lai gia chut nht v ngi cn li ton b nhim sc th ca chut v cn khong 7 nhim sc th ca ngi mt s t bo ch cn 1-2 nhim sc th ngi. S xc nh v tr ca mt gen trn mt nhim sc th nht nh c cn c vo s tn ti hay mt i ca gen khi i chiu vi s hin din hay vng mt nhim sc th trong dng t bo. K thut ny gip vt qua kh khn khi thng k theo ph h v nh n m gn trm gen c xc nh v tr trn 23 nhm lin kt gen. Trong trng hp gen TK, dng t bo chut TK- c lai vi t bo ngi TK+. S dung hp to t bo lai chut-ngi. Mc d phn ln nhim sc th ngi b loi mt nhanh trong cc dng t bo lai, nhng mt s dng cn mt t nhim sc th ngi. Khi cc dng t bo ny c nui trn cc mi trng c cht aminopterin, cc t bo TK - sai hng hot tnh thymidin kinase, khng mc c do mt kh nng chuyn ha thymidine thnh thymidylic acid cn cho tng hp ADN. Do vy ch c t bo lai c nhim sc th 17 ny ca ngi mi to c dng n nh. Chng t gen TK+ phi nm trn nhim sc th ny. Chng c xc nhn thm c thc
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hin bng cch chn cc dng trn mi trng c thm cht bromodeoxyuridin riboside (BUDR) l cht ng ng vi nitrogenous base c chuyn ha bi thymidin kinase (TK+) gn vo ADN lm t bo cht. Hu qu, nui trn mi trng c BUDR l cc dng t bo sng c khng c gen TK+ v tng ng vi iu , chng khng c nhim sc th 17 ca ngi. Da vo phng php ny, ngi ta lp bn nhim sc th ngi trn c s s c mt ca mt sn phm do mt gen no th tng ng vi s c mt nhim sc th trong t bo. - iu kin thc hin c vic lp bn nhim sc th ngi nh phng php ny + Tnh trng nghin cu c m ha bi mt gen trn nhim sc th ca ngi, m n c phn bit r rng vi tnh trng tng ng ca chut. V d: Dng t bo ngi cha Lactatdehydrgenase A t bin, enzyme ny phi c phn bit vi protein c m ha bi mt gen tng ng ca chut (LDHA ca ngi v chut c phn bit bng phng php in di). + Kh nng c th xc nh c nhim sc th ca ngi cn li dng t bo V d: gen LDHA ca ngi c pht hin trong cc dng t bo lai m trong ch cn li c nht mt nhim sc th. l nhim sc th s 2. Chng t LDHA nm trn nhim sc th s 2. Phn ln cc gen c xc nh theo phng php trn lin quan n cc enzyme, m vic pht hin chng cn c theo phn ng do chng xc tc. V sau mt s th thut khc c s dng nh dng cc "mt on" xc nh v tr gen. - Xc nh nhm lin kt ca cc gen bnh Da vo cc nhm lin kt gen c xc nh bng lai t bo soma, nhiu gen bnh c gn vo cc nhim sc th. Vic xc nh ny cn c theo nhiu ph h ca cc gia nh c cc bnh di truyn. Gn y (1993) vi bnh di truyn c xc nh bng cch s dng gen d tuyn (caniate gene approach). Mt trong cc v d l cc t bin ca gen fibrillin gy hi chng Marfan. Gen gy hi chng Marfan c lp
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bn nhm lin kt 15, ngay gia vai di ca nhim sc th. Gen m ha cho fibrillin cng c v tr tng t khi s dng phng php FISH (fluorescent in situ hybridization - pht hin bng hunh quang khi lai ti ch).
Cu hi n tp
1. C ch xc nh gii tnh ngi v ng vt. 2. c im ca s di truyn lin kt vi gii tnh. 3. C s ca s hnh thnh cc nhim sc th ti t hp. 4. Nu ng dng ca s di truyn lin kt vi gii tnh. 5. Chng minh trao i cho xy ra giai on 4 chromatid. 6. C s t bo hc ca trao i cho. 7. So snh quy lut di truyn lin kt hon ton v quy lut hon v gen. 8. Di truyn hc Morgan b sung cho di truyn hc Mendel nh th no?
Ti liu tham kho

Trnh Vn Bo, Phan Th Hoan, Trn Th Thanh Hng, Trn Th lin, Trn c Phn, Phm c Phng, Nguyn Vn Rc, Nguyn Th Trang. 2002. Cc nguyn l sinh hc. NXB Y hc H Ni. 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. 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.
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Tai lieu chia se tai: wWw.SinhHoc.edu.vn Di truyn hc Vi khun
Mc tiu ca chng
Gii thiu cac hin tng di truyn vi khun, s chuyn vi va c s di truyn tinh khang thuc cua cac vi khun gy bnh.
S tit: 3 Ni dung I. u th v cc c im ca i tng vi sinh vt

1. Thi gian th h ngn, tc sinh sn nhanh Trong iu kin thun li, t bo E.coli c th phn chia 1 ln trong 20 pht, cn bacteriophage trong thi gian 30-40 pht c th to ra hng trm c th, nm men c th chia t bo trong 2 gi. c im nghin cu di truyn hc l theo di qua nhiu th h nn cc i tng vi sinh vt gip rt ngn ng k thi gian th nghim. Nu so snh thi gian th h ca rui gim (2 tun), ca chut (2 thng), ca ngi (20 nm) th cc vi sinh vt u th hn hn. 2. C s tng vt s lng c th Trong iu kin dinh dng cc vi sinh vt sinh sn nhanh to qun th c s lng c th ln, c th c s lng 1010 -10 12 t bo.. T bo E.coli c ng knh 1 m nu dinh dng th trong 44 gi c th to sinh khi bng qu t. Rui dm l i tng thun li cho nghin cu di truyn hc qun th, nhng cng ch t 105 - 106 c th. Nh s lng c th ln c th pht hin c cc s kin di truyn him hoi vi tn s 10 -810-11. Nh vy s lng c th ln s gip nng cao nng sut phn gii di truyn tc kh nng pht hin cc t bin v ti t hp c tn s xut hin rt nh.
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Tai lieu chia se tai: wWw.SinhHoc.edu.vn tch, Ngoi ra vic nui cy vi sinh vt khng cng knh, t tn din
mi trng nui cy d kim sot theo cc cng thc cht ch. 3. C cu to b my di truyn n gin vi sinh vt c cu to b my di truyn l DNA trn, d tin hnh th nghim trc tip trn DNA cng nh d chit tch, tinh sch, s locus cng t hn so vi cc sinh vt khc. Cc vi nm v vi to c th tn ti dng n bi (n) vi thi gian di trong chu trnh sng nn cc gen ln c th c biu hin ra kiu hnh. Ngoi ra cc vi sinh vt k trn cn c trng thi lng bi (2n) nn cng d dng thc hin phn tch ti t hp. Cc tnh trng vi sinh vt n gin. i vi cc tnh trng sinh ha hay tnh khng d s dng mi trng chn lc pht hin. 4. D nghin cu bng cc k thut vt l v ha hc a s cc vi sinh vt c cu to n bo nn qun th ca chng c ng nht cao hn so vi cc sinh vt c b my a bo bt ngun t nhiu loi m khc nhau. Cu to t bo vi sinh vt n gin, d cht tch tinh sch DNA C th nui vi sinh vt ng nht tc a s cc t bo nhng giai on pht trin gn ging nhau. V d: nm men nui trn mi trng c b sung acetat, tt c cc t bo nm men u to bo t. To Chlorella khi nui trong ti 18-19 gi, tt c chng u thc hin phn chia gim nhim.
II. c im ca di truyn vi sinh vt

- Khun lc (dng t bo) l 1 cm t bo c ngun gc t 1 t bo ban u - Chng: dng t bo mang 1 c im di truyn no . Cc t bin vi sinh vt thng c pht hin theo s bin i cc tnh trng sau: - Hnh thi: kch thc, hnh dng t bo hay khun lc, c mng nhn hay khng...
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Tai lieu s hinse tai: cc sc t, mu sc c trng... chia din ca wWw.SinhHoc.edu.vn - Sinh ha:
- Nui cy: kiu h hp, kiu dinh dng, nhu cu i cc nhn t tng trng... - Tnh khng: khng thuc, khng phage, chu nhit... - Min nhim: phn ng khng nguyn, khng th... Cc t bin c th xut hin ngu nhin hay do gy to nh cc tc nhn gy t bin. Mi gen c tn s t bin c trng. c im ca ti t hp vi khun: Cc sinh vt Prokaryote nh vi khun, virus c qu trnh sinh sn tng ng sinh sn hu tnh gi l qu trnh sinh sn cn hu tnh (parasexuality), qu trnh ny c cc c im: - S truyn thng tin mt chiu t t bo th cho sang t bo th nhn. - S to thnh hp t mt phn (merozygote). T bo th cho (donor) chuyn mt on ca b gen sang t bo th nhn (recipient), nn ch lng bi mt phn, cn cc phn khc n bi. - B gen thng ch l DNA trn, nn ch c mt nhm lin kt gen v ti t hp thc cht l lai phn t.
III. Sinh hc ca vi khun

1. Cu to t bo v sinh sn: T bo E.coli c chiu di khong 2 m. Bn ngoi c vch t bo, k trong l mng sinh cht. Mezosome l cu trc xp li ca mng sinh cht c th lin quan n phn bo cht di truyn to nn nucleotid. Cc tim mao gip cho s vn ng ca t bo. Thng tin ca t bo vi khun nm trn mt phn t DNA mch kp vng trn n c gi l genophore, hay "NST". Gn y pht hin thy rng t nht mt s vi khun DNA to thnh phc hp vi protein c tnh base hnh thnh si nhim sc nh histon NST Eukaryote. Ngoi ra mt s vi khun cn c thm plasmid l phn t DNA vng trn nh c kh nng sao chp c lp.
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Tai lieu chia se tai: wWw.SinhHoc.edu.vn DNA Phn t DNA gn trc tip vo mng sinh cht. S sao chp
to ra 2 bn sao gn chung nhau trn mng sinh cht. Khi t bo ko di ra cc bn sao DNA tch xa nhau do phn mng gia chng ln dn ra. Kiu sinh sn v tnh ny c gi l ngt i (Binary fission). T bo vi khun chia nhanh hn rt nhiu so vi t bo Eukaryote. Qu trnh sao chp DNA c bt u t im xut pht Ori ko di v 2 phiasong song vi qu trnh ko di mng sinh cht, ni c im gn vo ca DNA b gen, mc di tch 2 phn t DNA v 2 t bo con.
Hnh 7.1 t bo vi khun E. coli
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Hnh 7.2 T bo vi khun phn chia theo trc phn.
2. c im nui cy T bo vi khun c th nui trn mi trng lng c b sung cc mui v c thit yu. Mt c th t 109 t bo/ml. C th nui vi khun trong mi trng rn c agar trong cc hp petri tng t bo mc thnh khun lc d quan st.
IV. Bin np ( Transformation)

1. Hin tng v iu kin - nh ngha: bin np l hin tng truyn thng tin di truyn bng DNA.
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Tai lieu chia se tai: wWw.SinhHoc.edu.vn Hinh 7.3 Bin nap cua vi khun
Trong bin np DNA trn t mt t bo vi khun th cho ny c truyn sang t bo vi khun th nhn khc. Khi t bo vi khun b v do lm tan, DNA vng trn ca chng thot ra mi trng thnh cc on thng vi chiu di khc nhau c kh nng gy bin np cho cc t bo th nhn khc. Hin tng bin np c nghin cu nhiu cc i tng: Streptococcus pneumoniae, Bacillus subtilis, Haemophilus parainfluenzae - iu kin thc hin bin np: Hiu qu ca bin np ph thuc vo 3 yu t: + Tnh dung np ca t bo th nhn. Nhng t bo dung np trn b mt c cc nhn t dung np. Ngi ta c th to kh nng dung np ca t bo th nhn bng mt s x l. V d: Streptococcus pneumoniae: 30 - 80 im nhn Haemophilus influenzae: 4-8 im nhn + DNA thc hin bin np ca th cho phi dng mch kp, nu DNA b bin tnh dng mch n ring l khng cho hiu qu bin np. Thng DNA bin np l mt on nh. vi khun E.coli on DNA bin np khong 1/250 - 1/500 genom ca vi khun. on t t bo cho xm nhp vo t bo nhn c gi l on ngoi lai (exogenote), DNA nguyn vn ca t bo nh c gi l on ni ti (endogenote). T bo vi khun nhn on ngoi lai s lng bi mt phn b gen c gi l hp t tng phn (merozygote). Tuy nhin, on ngoi lai mch n khng bn vng v b phn hy nu khng c gn vo b gen th nhn. Qu trnh trao i thng tin di truyn bng chuyn ch mt phn vt liu di truyn t t bo ny sang t bo khc c gi l s giao np tng phn (meromixis). 2. C ch bin np 2.1. Xm nhp ca DNA giai on ny, DNA c th gn vi im nhn ca mng t bo.Qu trnh gn ny c th l thun nghch, n c th gn vo ri nh ra.
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Si DNA mch kp ca dng vi khun S sau khi chui qua mng t bo ca dng vi khun R th mt mch ca S s b nuclease ca t bo ct, cn li mt mch nguyn.
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Hinh 7.4 C ch bin nap t nhin
2.2. Bt cp DNA ca th nhn R s bin tnh tch ri 2 mch mt on bt cp vi on DNA th cho S va chui vo. on DNA ca R on c DNA ca S bt cp s b ct t v y ra. Trong qu trnh bt cp, c nhng on khng tng ng th s hnh thnh nn nhng vng li, nhng on gi l Heteroduplex. Cn cc on bt cp tng ng gi l Homoduplex. 2.3. Sao chp Sau khi bt cp s to phn t DNA c on lai R-S, tin hnh sao chp to ra hai si kp: mt si kp R-R v mt si kp khc c mang on DNA th nhn S-S.
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Hnh 7.5 S cc giai on bin np
V. Ti np (Transduction)
1. Phage l nhn t chuyn gen Th nghim c tin hnh trong ng hnh ch U. Gia hai ng ca hnh ch U c ngn cch bng mng lc vi khun, mng c l nh vi khun khng qua c nhng phage qua c. Nhnh A ca ng cha vi khun c kh nng tng hp tryptophan (trp+), cn nhnh B nui cc vi khun khc mt kh nng tng hp tryptophan (trp-). Sau khi nui mt thi gian, nhnh B xut hin vi khun c kh nng tng hp tryptophan. Nu dng mng ngn khng cho virus lt qua th khng thy hin tng ny. Qua nhiu ln th nghim, vic ti gen trp+ t nhnh A sang nhnh B c chng minh.
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Hnh 7.6 Th nghim chng minh hin tng ti np
2. c ch Qu trnh xm nhim ca phage vo vi khun xy ra nh sau: Ti np chuyn gen t vi khun A sang B nh phage u tin cc phage bm trn b mt vi khun. Sau 4, phage bm DNA ca n vo t bo. Sau chng sinh sn v khong 1/2 gi sau th chng lm tan cc t bo vi khun v gii phng cc phage mi. Khi DNA ca phage xm nhp vo t bo vi khun A, chng ct DNA ca vi khun A thnh nhiu on ng thi DNA ca phage c sao chp ra nhiu phn t con v cc v phage cng c to thnh. Sau cc v lp rut DNA vo, ph v t bo vi khun ra ngoi v tip tc xm nhim vo cc t bo vi khun khc. Trong qu trnh lp rp khong 1-2% phage v tnh mang on DNA ca vi khun c cha gen. Phage mang gen vi khun A xm nhim vi khun B, qu trnh ti t hp xy ra lm gen vi khun A gn vo b gen vi khun B.
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Hinh 7.7 Chuyn gen t vi khun cho sang vi khun nhn nh phage
3. Phn bit cc dng ti np - Ti np chung (general transduction): phage mang bt k gen no ca vi khun A sang vi khun B. Ti np chung c c im: + Bt k gen no ca vi khun cng u c ti np + Ti np do gi nhm DNA ca t bo ch khi phage trng thnh + Cc th ti hp n bi c to ra - Ti np chuyn bit (Special transduction) hay ti np hn ch: l qu trnh ti np ch chuyn mt vi gen nht nh, n c 4 c im: + Nhng gen c chuyn nm st ch phage gn vo + Ch prophage kiu thc hin + Do kt qu s ct sai ca prophage khi tch khi NST ca t bo ch V d: phage (k sinh trn E.coli) ch chuyn gen gal (ng ha ng galactose) t vi khun ny sang vi khun khc. im gn ca phage vo b gen ca vi khun nm gia 2 gen gal (galactose) v bio (tng hp biotin). u ca phage ch c th cha mt lng DNA gii hn, nn khi prophage tch ra t DNA ca vi khun n ch ti np c gen gal hoc bio. S ct sai ca phage rt him nn ti np hn ch c tn s thp.
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Hnh 7.8 Ti np chuyn bit
VI. Giao np (Conjugation)

- nh ngha: giao np l hin tng truyn vt cht di truyn t t bo th cho sang th nhn qua cu t bo cht
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Hnh 7.9 S lai vi khun
1. Chng minh c lai vi khun Vo nm 1946, J. Lederberg v E. Tatum s dng cc dng t bin khuyt dng khc nhau: -Dng A: c kiu gen met-bio-thr+leu+thi+ (c kh nng tng hp threonin, leucine, thiamin khng c kh nng tng hp methionin v biotin) - Dng B: c kiu gen met+bio+thr-leu-thi- (c kh nng tng hp methionin, biotion nhng khng c kh nng tng hp threonin, leucine, thiamin) Tng dng ring r khi cy ln mi trng ti thiu th khng c kh nng mc ln khun lc. Trn chung hai dng ny trong ng nghim, cy ln mi trng ti thiu. Cc khun lc mc trn mi trng ti thiu, chng t c cc dng lai, chng mc c nh s b p cho nhau nhu cu dinh dng. Cc dng lai c kiu gen met+bio+thr+leu+thi+. 2. S phn ha gii tnh vi khun 1953, Hayes pht hin ra vi khun c cc dng khc nhau tng t ging c v ci sinh vt bc cao. Cc dng c k hiu l t bo F +
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v t bo F- . F+ tng t ging c sinh vt bc cao, n truyn sng F-. Tn s lai F+ vi F- khong 10-6. Khi F+ tip xc vi F- mt thi gian, F- bin thnh F+ do n nhn c mt phn t di truyn l episome. Episome F+ l phn t di truyn ngoi NST, c th tn ti hoc dng DNA vng trn t sao chp hoc gn vo phn t DNA ca t bo ch. Episome F+ c gi l nhn t gii tnh. V sau dng Hfr (high frequency recombination) c pht hin, dng ny c tn s lai vi F- cao hn F+ c th n 104 ln.
Hnh 7.10 S cu tao cua plasmid
Plasmid c nh ngha l phn t DNA vng trn nh c kh nng sao chp c lp vi t bo ch v khng c kh nng gn vo NST t bo ch. Plasmid c th mang mt s gen khc nhau. Hin nay plasmid c dng cho c 2 ngha l episome v plasmid. Plasmid c th tn ti c lp hoc gn vo b gen vi khun. Bn cht di truyn ca cc dng F-, F+ v Hfr c xc nh do cc plasmid nh sau: F- khng cha plasmid F+ cha plasmid dng c lp Hfr c plasmid gn vo b gen
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Hinh 7.11. S gn cua plasmid vao nhim sc th vi khun tao vi khun Hfr
- Tai t hp gia mt trinh t IS trn plasmid va trinh t IS cung loai trn nhim sc th cua vi khun tao ra nhim sc th Hfr - Tai t hp xay ra gia IS bt ky trn plasmid vi IS bt ky tng ng trn nhim sc th cua vi khun tao ra nhiu chung Hfr khac nhau 3. Cc nhn t F' v tnh np (Sexduction)
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Tai lieunhn t F t tai: wWw.SinhHoc.edu.vn xc chia se NST ca dng Hfr nhiu khi khng chnh S ct ri
v lc ny mt on b gen ca vi khun thay th cho mt phn ca F. Trong trng hp ny nhn t F' c hnh thnh v n c th chuyn gen ca vi khun mt cch c lp vi cc tnh trng ca t bo th cho. Hin tng ny cn gi l tnh np, ngha l s chuyn gen km theo nhn t gii tnh. Nh tnh np m c th nhn c nhng th lng bi tng phn (merodiploid) theo cc gen c gn vo F+. 4. C ch ti t hp Khi c s tip xc gia hai loi t bo khc du nh Hrf v F - hoc F+ v F-. Dng t bo mang nhn t F+ c coi l t bo c c kh nng to protein pilin, t protein ny to ng giao np gi l pilus. S co li ca pilus ni 2 t bo lm chng gn nhau. T bo F- c coi l t bo ci, sau khi giao np t bo F- tr thnh t bo F+. Vic chuyn gen ch thc hin khi plasmid gn vo b gen ca vi khun. Trong qu trnh chuyn vt cht di truyn sang F- th DNA ca t bo ch sao chp v mch mi c Ori i u v F i cui. Qu trnh chuyn DNA t F+ sang F- c th b ngt qung. Cc gen a, b, c c chuyn mt chiu t Hfr sang F-. Dng Hfr c tn s lai cao hn nhiu v plasmid nm sn trong b gen. Cn F+ phi qua giai on plasmid gn vo b gen ri mi chuyn gen.
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Hinh 7.12 Thi nghim giao nap lp ban do ngt quang cac khoang thi gian khac nhau.
S truyn DNA t t bo th cho sang t bo th nhn Trong iu kin th nghim 370C, nguyn b gen ca t bo E.coli c chuyn sang t bo nhn trong vng 90 pht. Thng s giao np b ngt qung gia chng do cu pilus b gy, lc t bo F- vn l t bo F-. Bng cch ngt qung qu trnh giao np m bn di truyn ca E.coli c xy dng nn c dng vng trn.
VII. C s di truyn tnh khng thuc ca cc vi khun gy bnh ngi. ngha ca cc transposon vi khun
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Tai transposon vi khun l nhng yu t lm thay i v tr gen, lieu chia se tai: wWw.SinhHoc.edu.vn Cc
kim sot tnh khng thuc i vi thuc khng sinh v cc thuc chng vi khun khc. Chng c th d dng truyn t t bo ny sang t bo khc. Ngay sau , ngi ta xc nh l cc gen khng thuc thng c trong plasmid. Cc plasmid c th c truyn t t bo m sang t bo con khi t bo va phn chia. Trong iu kin thc nghim cho thy 100% qun th t bo nhy cm thuc u c th tr thnh khng thuc sau thi gian 1 gi c trn vi vi khun khng thuc. Cc gen khng thuc c th c truyn t plasmid cho NST vi khun, cho virus v c cho vi khun cc loi khc. Mi plasmid R u c ti thiu 2 thnh phn: - Mt on mang gen v truyn AD tip hp (tng t nh transposon ca plasmid F) - Mt on mang gen khng thuc on th nht gi l yu t lm vt truyn tnh khng (RTF Resistance transfer vector). on th hai mang gen khng c gi l yu t khng R (R - determinant). mt s plasmid R, yu t khng R c ci gia cc on xen IS. Trong nhiu trng hp chng lm cho yu t khng vn ng t plasmid R ny sang plasmid R khc. Cc on IS thc y s tin ha nhanh ca cc plasmid vi khun ngy cng mang nhiu yu t khng thuc. Khng phi nhng plasmid ny ch c truyn i trong phm vi mt loi vi khun. M chng cn c truyn qua cc loi v c cc dng di truyn khc nhau ca vi khun. V d: plasmid R ca E.coli c pht hin mt s ging nh proteus, Samonella, Haemophilus, Pastugella... Tt c cc loi ny u l loi gy bnh. Ngy nay ngi ta thy tn s tng ln r rt ca cc vi khun mang plasmid R vi yu t khng R c sc khng gh gm vi cc thuc khng sinh: penicylin, tetracylin, streptomycin v kanamycin. Cc nghin cu Nht Bn cho bit trong vng 10 nm tr li y, qun th vi khun t nhin (trong cng, rnh, h, ao b nhim) tng hn ln, t tn s thp l di 1% plasmid R c s khng thuc ln n tn s cao l 50-80%.
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Tai kt qu nu trn tai:thy, cn hn ch v lu ch s dng lieu chia se cho wWw.SinhHoc.edu.vn Cc

khng sinh khi c nhim trng v khng nn lm dng i vi cc trng hp nh. Nu khng hn ch th trong tpng lai thuc s gim hiu qu hoc khng cn hiu qu. Tnh khng thuc ngy nay c pht hin trong nhiu loi gen gy bnh nh gen thng hn, vim d dy, rut, dch hch, st cao, vim mng no, lu ...
Cu hi n tp 1. Phn bit cc ni vi khun F+, F- v Hfr E. coli

2. Trnh by c ch bin np 3. Phn bit ti np chung v ti np c hiu. 4. So snh bin np v ti np. 5. Th ti t hp cc gen khc nhau theo thi gian xy ra trong giao np nh th no? 6. c im ca ti t hp vi khun.
7. T bo F- hnh thnh t bo F+ v t bo Hfr nh th no? Ti liu Tham kho

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 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. Cann AJ. 2001. Priciple of molecular virolory. Academic Press. London, UK. Flint SJ, Enquist LW, Krug RM, Racaniello VR, Skalka AM. 2000. Principles of Virology. Molecular Biology, Pathogenesis, and Control. ASM Press, Washington DC. Printed in the United States of America.
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Harlt D.L., Jones E.W. 1998. Genetics - Principle and analysis. Jone and Bartlett Publshers, Toronto, Canada. Hartwell et al. 2003. Genetics: From genes to genomes, Second editor. The McGraw-Hill Companies. Old RW & Primrose SB. 1989. Principles of gene manipulation. Blackwell Scientific Publication. Stansfield W.D. 1991. Schaums outline of theory and problems of 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. Benjamine Cummings, San Francisco, United States of America.
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Chng 8
Tai lieu chia se tai: wWw.SinhHoc.edu.vn Di truyn hc Virus
Mc tiu ca chng
Gii thiu s di truyn ca thc khun th, nghin cu s sp xp cc gen, cc c tnh ca virus v, trn c s bn cht ca genome ca virus xc nh kiu sao chp.
S tit: 3 Ni dung I. Di truyn hc th thc khun (Bacteriophage hay phage)

1. S hnh thnh vt tan v cc th t bin phage Phage c pht hin d dng v trong chu trnh tan, mt t bo b nhim phage v ra v gii phng cc ht phage vo mi trng (Hnh 8.1). S to thnh cc m c quan st. Mt s ln t bo vi khun (khong 108 t bo) c tri ln trn mi trng c. Sau mt thi gian sinh trng, to mt lp t bo vi khun mu trng c. Nu phage c mt thi im vi khun c tri ln mi trng, n s nhim vo t bo vi khun. Sau t bo nhim phage b lm tan v gii phng nhiu phage mi. Th h sau ny ca phage li nhim vo vi khun gn , v tham gia vo chu trnh tan khc, cc vi khun ny b v gii phng ra nhiu phage, chng c th nhim vo cc vi khun khc vng ln cn. Chu trnh xm nhim ca phage c tip tc v sau nhiu gi, phage ph hu tt c cc t bo vi khun ca mt vng, to m (plage) trong sut khc vi lp t bo vi khun mu trng c.
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T bo khng b xm nhim
Phn hy t bo ch
Phage hp ph ln t bo ch
Phage t do
Phage lp ghp bn trong t bo ch
Chu trnh sinh tan

Nucleic acid ca phage Phage protein
Vt cht di trun t bo ch b ph hy
Nucleic acid ca phage xm nhp vo t bo
Protein ca phage c tng hp, acid nucleic c nhn ln, vt cht di truyn t bo ch b ph hy
Hnh 8.1. Chu trnh sinh tan ca bacteriophage
Hnh 8.2. S xm nhp ca phage vo t bo vt ch theo c 2 dng b m ng thi. r : m nh, r : Tai lieu chia sem ln, h : m m, h : m trong tai: wWw.SinhHoc.edu.vn
+ + -
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Phage ch c th c nhn ln ch khi sinh trng trong t bo vi khun, v vy lm cn ngun dinh dng trong mi trng sinh trng, lm hn ch s nhn ln ca phage v kch thc ca m. V mi m l kt qu ca s nhim mt ht phage ban u, c th m c s lng cc m ring bit c trn mi trng (Hnh 8.2). Kiu gene ca cc th t bin phage c th c xc nh nh nghin cu cc m. Trong mt s trng hp, s xut hin ca cc m l y . Chng hn, t bin phage lm gim s lng phage th h sau t nhng t bo b nhim thng to m nh hn. Cc m ln c th c to ra bi cc t bin gy ra s tan sm cc t bo b nhim, nn mi m tip tc nhim nhanh hn. Kiu t bin khc ca phage c th c xc nh bi phage c kh nng hoc khng c kh nng to m trn nhng chng vi khun c bit. 2. Ti t hp di truyn trong mt chu k sinh tan (Lytic cycle) 2.1. Chu trnh tan (Lytic cycle)
Hinh 8.3 S kt hp u va ui tao phage hoan chinh
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Tai bacteriophagese tai: wWw.SinhHoc.edu.vn sn lieu chia lm cht t bo ch gi l c, chng sinh Cc

theo chu trnh tan. Chu trnh bt u khi si ui ca phage gn vo im nhn b b ngoi ca E.coli. ng ui co li to l thng xuyn vch t bo v bm DNA ca n vo. Capside ca phage cn li bn ngoi t bo. Sau khi b nhim cc t bo E.coli c qu trnh phin m v dch m cc gen ca virus. Phage T4 c khong 100 gen v phn ln c bit r. Mt trong nhng enzyme c to ra u tin ct DNA ca t bo ch. DNA ca phage c phin m u tin nh DNA polymerase ca t bo ch to ra mARN sm. Cc mARN mun hn c th c tng hp bi ARN polymerase ca phage hoc ARN polymerase ca vi khun b bin i phin m cc gen ca phage. Cc mARN mun c dch m to cc loi protein enzyme iu ha v cu trc. Cc protein iu ha ca phage kim sot s phin m ni tip ca cc gen. Khi DNA ca t bo ch b phn hy, b gen ca phage kim sot ton b hot ng ca t bo to ra cc cu phn ca n. DNA ca phage c sao chp ra hng trm bn sao. Cc protein ca capsid c tng hp thnh 3 phn ring: u, ng ui v cc si ui. Chng t rp vi nhau thnh cc virion con. Phage hon tt chu trnh khi enzyme lysozyme c to ra tiu ha vch t bo vi khun. T bo vi khun b v, 100-200 virion thot ra v chng c th lp li chu trnh mi. Ton b chu trnh t lc phage tip xc n tan din ra trong khong 20-30 pht 370C. Trong thi gian s lng phage T4 tng hn c 100 ln, trong khi s lng t bo E.coli mc nhanh nht cng ch tng gp i. Phn ln cc phage c theo chu trnh va nu trn. Tuy nhin c mt s ngoi l nh phage si M13 ca E.coli hu nh khng bao gi lm cht hoc lm tan t bo. Cc t bo vi khun v cc phage k sinh c s ng tin ha. Cc t bo vi khun c cc c ch bo v nh bin i mng t bo phage khng bm vo c hoc cc enzyme ct hn ch ct DNA ca phage. Phage cng bin i xm nhp c vo t bo vi khun. Cc phage tuy c kch thc nh b phi nhn di knh hin vi in t mi thy c. Nhng cc tnh trng ca phage c quan st da theo cc vt tan hoc bin ch. Cho hai dng phage T4 c kiu gene khc nhau nhim vo mt t bo vi khun E.coli, mt vi phage th h sau s thc hin
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ti t hp di truyn. Allele r- tan nhanh, kt qu to ra m ln, allele hnhim vo cc t bo ch, kt qu to m trong. Php lai nh sau: r-h+ r+hKt qu thu c bn kiu m. Hai kiu m c, ln v m trong, nh tng ng vi kiu hnh ca phage b m. Hai kiu hnh khc, m trong ln, m m nh l dng ti t hp tng ng kiu gene r-h- v r+h+. Khi nhiu vi khun b nhim s dng ti t hp thun nghch thng c tm thy trong s cc phage th h sau. Trong th nghim, mi kiu gene trong s bn kiu gene trn sinh ra kiu hnh khc nhau v dng m (Hnh 8.2). S lng kiu gene c th xc nh c bng kim tra cc m to thnh. Tn s ti t hp, c biu din di dng phn trm, c xc nh nh sau: Tn s ti t hp = S phagetait hp 100 Tng s phage
3. S sp xp ca cc gene trong nhim sc th phage Tn s ti t hp c th c s dng xc nh khong cch ca bn Eukaryote. Cc th nghim lp bn cho thy t bin T4 c lp bn thnh 3 cm ring bit. C ba cm ny c lin kt vi mt cm khc. George Streisinger v cng s (1964) chng minh bn di truyn ca phage T4 c dng vng trn. Trong mi php lai, lp ba n bn marker di truyn ln lt vi mi nhm v tin hnh qua ton b genome ca T4. Nhiu gene khc c xc nh v lp bn y trn phn t vng trn (Hnh 8.3). Nhng vng vng trn bn trong l 3 cm ca marker T4 c xc nh v lp bn di truyn. Vng ngoi c mt ca nhiu b marker ln to thnh ton b vng trn ca bn di truyn. Bn di truyn phage T4 cho thy gene ca phage T4 to cm m rng theo chc nng ca chng. Chng hn c cm ln cc gene dng cho sao chp DNA v tr phn t bn trn pha phi v c cm gene tng hp cc cu phn to nn u ca phage pha di ca vng trn. Phn t DNA ca phage T4 l phn t si n dng thng, mi u tn cng ca DNA phage T4 c nhn ln hoc lp on u cui (terminal redundant). Do vy, mi phn t DNA c kch thc tng thm 2%. Khi DNA c sao chp trong t bo, s ti t hp gia cc phn u
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tn cng ca b gen T4 vi nhng trnh t tng ng ca b gen T4 khc, kt qu to ra sn phm DNA c kch thc ln hn kh nng cha ca phn u. Nhng phn t cha lp on c to thnh v s ti t hp trong b gen ca phage T4 xy ra thng xuyn, trung bnh c khong 20% s kin ti t hp xy ra trn mt nhim sc th. Khi phn t DNA c gi vo phn u, n c ct bng enzyme ch cn cha khong 102% ca chiu di b gen phage T4, v c cha on lp li ca phn u.
Mng Si ui Trao i nucleotide Tng hp DNA, ti bn v thay i Nhm gen lin kt xc nh ngun gc a gc ca ui
u, c, np gp c a gc ca ui u
Hnh 8.4. Bn di truyn ca T4 vi cc marker
4. Lp bn cu trc tinh vi vng rII ca phage T4 Cc nghin cu chi tit v cc t bin rII ca phage T4 lm sng t hn v cu trc gene. Phage T4 dng hoang di r+ c kh nng nhim ng thi hai ni E.coli B v K. Cc t bin rII ch nhim ni B nhng khng nhim ni K. Seymour Benzer (1955) nhn c 2400 t bin rII c ngun gc c lp vi nhau. ng cho lai cc t bin vi nhau v cn c vo s xut hin cc dng ti t hp hoang di r+ m lp bn cc im t bin. Mi t bin c th ti t hp vi cc t bin khc. t bin mt on ngn cn s ti t hp vi hai hoc nhiu t bin im cc v tr khc nhau ca gene. Mi mt on lm mt mt phn b gene ca phage Tai lieu chia se tai: wWw.SinhHoc.edu.vn 147
bao gm c vng rII. S dng t bin mt on l phng php n gin lp bn ca hng ngn t bin. Bn mt on (Deletion mapping) da trn s c hoc khng c dng ti t hp. Trong bt k php lai no gia mt t bin im cha bit v mt t bin mt on, s xut hin ca dng hoang di cho thy t bin im nm ngoi vng mt on. Ngc li, nu t bin im xut hin trong vng mt on, khng xut hin dng ti t hp kiu hoang di th h sau.
rII A cistron rII B cistron
Khong cch t A1 n B c xc nh bng mt on cc khong 1272 qua 638
Khong cch t 1 n 47 c xc nh bng mt on khong 1364 qua 1519
Hnh 8.5 t bin mt on c s dng chia locus rII ca bacteriophage T4 thnh 7 vng v 47 tiu vng nh
Nhiu php lai c thc hin lp bn t bin chi tit gene rII. Khong cch t A1 n A6 v B c trnh by hnh 8.4. Mt t bin c bit c kim tra nh v vng A4. t bin ny khng ti t hp to dng kiu di trong php lai vi cc t bin mt on ln nh r1272, r1241, rJ3 v rPT1 nhng n c th ti t hp to dng kiu di trong php lai vi rPB242, rA105 v r638. Cc t bin c to ra bi cng mt khun, kt qu lai vi cc t bin mt on ln s c xp vo vng A4. Bn di truyn trong vng A4 c th c to ra bi mt b cc t bin
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mt on c trnh by phn di ca hnh 8.5. Xc nh 7 tiu vng trong A4 (t a qua g).
rII A cistron
rII B cistron
Vng xc nh t bin mt on t A1 n A6 v B trong gen rII
t bin trong vng b s to ra dng ti t hp hoang di vi tt c cc mt on m trong vng b ca dng hoang di c mt
Mt on vng xc nh a n g ca vng A4
Hnh 8.6 Xc nh vng rII lin quan vi cc marker di truyn dng thng ca bn di truyn phage T4
V d, mt t bin trong vng A4 kt qu ti t hp to dng kiu di vi t bin mt on r1368, nhng li khng th thc hin c vi t bin r221 s c sp vo tiu vng c. mc chi tit hn, cc t bin trong mt tiu vng c sp xp nh lai gia chng vi nhau. phage T4, cc im t bin rt gn nhau, c tch nhau nh ti t hp. 1% ti t hp tng ng vi khong cch khong 100 bp. V vy, bt k hai t bin khng th ti t hp c vi nhau c th c xp vo cng v tr trong gene. Bn di truyn cho s ln cc t bin rII c ngun gc c lp c m t hnh 8.6. Nghin cu t bin vng rII v lp bn di truyn c vai tr quan trng, qua c th rt ra cc kt lun sau: + S trao i di truyn c th xy ra trong gene v c th gia cc nucleotide gn nhau.
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+ Cc t bin khng c to ra cng tn s vi tt c cc im trong gene, chng phn b khng u nhau. Chng hn, 2400 t bin rII c xc nh ch 304 im. Mt trong nhng im ny c th c n 474 t bin (Hnh 8.6). Nhng im c tn s t bin cao nh th c gi l cc im nng (hotspot mutation). nhng im khc, t bin c phc hi mt ln hoc vi ln.
Mi hp th hin s xut hin ngu nhin ca cc t bin ti v tr
"im nng" t bin
Nhiu t bin xut hin mt im to thnh mt "im nng"
Hnh 8.6 Bn di truyn locus rII ca phage T4
Kt qu phn tch vng rII rt quan trng, gip cho chng ta phn bit c 3 khi nim v gene. Ph bin nht, gene lin quan vi mt n v chc nng. iu ny tng ng vi mt on DNA m ha cho mt phn t protein. Benzer a ra thut ng cistron ch chc nng ny, thut ng cistron thnh thong vn c s dng. n v chc nng c xc nh qua th nghim b sung (complementation test), xc nh c 2 t bin c allele vi nhau khng. Trc th nghim ca ng rII c coi l mt locus. Th nghim cho thy cc t bin xp thnh hai nhm rIIA v rIIB. Lai cc t bin rIIA
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rIIB s c r+, nhng lai rIIA rIIA v rIIB rIIB th thu c kiu hnh t bin r. Ngoi ngha l n v chc nng, gene cn l n v ti t hp (recon) v n v t bin (muton). C hai n v ny, u tng ng vi nhng nucleotide ring l trong gene. 5. Tnh tim tan (Lysogeny) v phage Chu trnh tim tan bt u khi phn t DNA ca phage gn vo nhim sc th ca vi khun v tin hnh sao chp nh mt phn nhim sc th vi khun. Cc ht phage khng c to thnh. Phn t DNA ca phage c gn vo b gen ca vi khun c gi l prophage, t bo vi khun sng st c gi l t bo tim tan (lysogen). Mt chng tim tan cho phage c k hiu theo tn ca phage. V d chng E. coli K12() l chng K12 tr thnh t bo tim tan ca phage .
Phage
Phage DNA
Phage tn cng t bo ch v bm DNA vo
NST vi khun
Mt s prophage tn ti trn NST vi khun, khi u cho chu trnh sinh tan Nhiu t bo phn chia to ra khun lc vi khun c cha prophage
T bo b phn gii, gii phng phage
Chu trnh sinh tan
Ti to vng DNA phage
DNA v protein ca phage c tng hp v lp ghp to thnh phage mi
T bo vi khun phn chia bnh thng, sao Prophage chp prophage v truyn cho th h sau DNA ca phage tch hp vo NST vi khun to thnh dng prophage
Chu trnh tim tan
Hnh 8.7 Chu trnh tan v tim tan phage
Phn t DNA ca phage c u cc u cui cha 12 nucleotide khng kt cp, m dng si n to u dnh (cohesive end) b sung. Khi vo t bo, u cui b sung gn li to phn t vng trn. S to vng trn xy ra sm c chu trnh tan v chu trnh tim tan (Hnh 8.7). C khong 75% t bo vi khun b nhim phage, phn t DNA vng trn sao chp v
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chu trnh tan xy ra tip theo. Cn khong 25% t bo b nhim, phn t DNA vng trn ca phage v phn t DNA vng trn ca E. coli tng tc v xy ra ti t hp im chuyn bit (site-specific recombination) v DNA ca phage gn vo nhim sc th ca vi khun. V tr ca ti t hp im chuyn bit DNA ca vi khun v phage c gi l im gn vo ca vi khun v phage (bacterial and phage attachment sites). Mi im gn c cha 3 on: on trung tm c cng trnh t nucleotide c 2 v tr gn v l vng m s ti t hp thc s xy ra. im gn vo ca phage c k hiu bi POP (P: phage) v im gn vo vi khun c biu din bng BOB (B: bacteria). So snh bn di truyn ca phage v prophage POP nm gn vng trung tm ca phn t DNA dng thng. Mt protein ca phage, integrase, xc tc cho ti t hp im chuyn bit. Enzyme integrase nhn ra im gn vo ca phage v vi khun, gy ra s trao i vt l, kt qu l phn t DNA ca phage gn vo phn t DNA ca vi khun. Kt qu ca s ti t hp lm bn di truyn ca prophage khc vi bn di truyn ca phage. Bn di truyn prophage l s chuyn i vng trn bn di truyn phage t do. Prophage c chn vo nhim sc th ca E. coli gia gene gal v gene bio. S chn vo ca phage lm tng khong cch gia gene gal v gene bio. Khong cch gia gene gal v gene bio t bo tim tan vi phage l khong hai pht so vi mt pht t bo khng tim tan.
Hnh 8.8 M hnh gn ca phage vo NST ca E.coli
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Khi t bo tim tan, cc gene ca phage tr thnh mt phn nhim sc th ca vi khun v vy c th lm kiu hnh ca vi khun b thay i. Nhng hu ht cc gene ca phage prophage u c gi trng thi bt hot nh protein repressor - sn phm ca gene phage. Protein repressor c bt u tng hp nh s nhim vo ca phage v n c tip tc tng hp nh prophage. Gene m ha cho repressor thng ch l gene ca prophage c biu hin chu trnh tim tan. Nu t bo tim tan b nhim bi phage ging vi prophage, s c mt ca repressor trong prophage ngn cn s biu hin cc gene ca phage nhim vo. Tnh khng vi nhng phage ging vi prophage c gi l tnh min nhim (immunity). y l tiu chun xc nh t bo vi khun cha phage c bit. Chng hn phage khng to m trn vi khun cha prophage . Trong t bo tim tan, s sao chp khng gii phng cc phage mi. Tuy nhin, cc prophage i khi tr nn c hot tnh, tri qua chu trnh tan, to ra s lng ln phage th h sau. Hin tng ny c gi l s cm ng prophage (prophage induction), n c bt u bng s h hi DNA ca vi khun. i khi prophage c th tch ra khi DNA ca vi khun mt cch ngu nhin nhng thng n c gy ra do cc tc nhn ca mi trng nh ha cht hoc chiu x. Kh nng b cm ng l mt thun li cho phage bi v DNA ca phage c th thot khi t bo b h hi. C ch sinh ha ca s cm ng l phc tp nhng s thot ra ca phage xy ra d dng. S ct ra ca phage l s ti t hp im chuyn bit khc, ngc vi qu trnh gn vo. S ct ny yu cu enzyme ca phage, integrase thm protein ca phage l excisionase. Nghin cu di truyn ca s gn vt l cho thy escisionase gn vi integrase v sau nhn ra im gn vo ca prophage BOP v POB, gn vi cc im ny. Integrase ct trnh t O v to ra li BOB v POP. Qu trnh tch din ra ngc li vi s gn vo.
II. c tnh ca cc virus

1. Tnh a dng v cu trc v thnh phn di truyn Virus c b gene rt a dng. B my di truyn ca virus c th l DNA mch kp (double strand - dsDNA), DNA mch n (single strand ssDNA), RNA mch kp (dsRNA) hay RNA mch n (ssRNA). B gene RNA ca virus l mt phn t hoc mt on, si n phn cc mch (+) hoc mch (-), c th dng vng trn hay dng thng. Virus nh nht c nht c khong 4 gene, virus ln c khong vi trm gene. B gene ca
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virus cu trc a dng nhng u m bo yu cu chung l phi sao chp c trong t bo ch to ra c genome cho lp rp virion th h sau v cc mRNA phi tng hp protein ca virus. 2. Tnh c th v vt ch (Host specificity) Mi kiu virus c th nhim v k sinh ch mt bin gii hn ca t bo c gi l bin ch (host range). Cc virus nhn bit t bo ch theo nguyn tc ng kha v cha kha cc protein bn ngoi ca virion lp va cc im nhn trn b mt t bo. Mt s virus c bin ch rng xm nhp vo vi loi. Chng hn, cc virus bnh di c th nhim nhiu loi c v gm gm nhm, ch v ngi. Bin c th rt hp nh nhiu phage ch nhim vi khun E. coli.
III. Ti bn ca cc virus
Bn cht genome ca virus xc nh kiu sao chp. Virus c phn loi da trn cc c im: - Phn loi theo bnh: chia ra virus gy bnh ngi, ng vt v cy trng Vn ch yu i vi h thng phn loi ny l nhiu loi virus khc nhau li gy ra cng mt triu chng. Chng hn, s nhim trng h hp vi st c th c gy ra do nhiu virus khc nhau. - Phn loi theo hnh thi: phn loi virus c bn da trn cu trc ca ht virus. Kiu phn loi ny c hn ch trong phn bit gia cc virus c hnh thi tng t nhng gy ra triu chng bnh khc nhau. - Phn loi theo chc nng: trong nhng nm gn y, nhiu nghin cu c tin hnh da trn phng thc sao chp ca virus. Cn xc nh thnh phn v cu trc genome ca virus v t xc nh cch sao chp. Kiu t bo b nhim bi virus c nh hng quan trng i vi qu trnh sao chp. i vi virus ca prokaryote, s sao chp phn nh mi quan h m rng n gin ca cc t bo ch. i vi virus ca t bo eukaryote, vn phc tp hn. Kh nng m ho ca genome buc virus chn mt phng thc sao chp. Phng thc sao chp ca virus ph thuc vo bn cht vt liu di truyn ca chng. V phng din ny, virus c chia thnh 7 nhm: Nhm I: Virus cha DNA si i. Nhm ny c chia nh thnh hai loi:
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+ Sao chp l ch ca nhn. S sao chp ca cc virus ny ph thuc tng i vo cc yu t ca t bo. + Sao chp xy ra trong t bo cht. Nhng virus ny c lin quan vi cc yu t cn thit cho phin m v sao chp genome ca chng v v vy ph thuc nhiu vo b my t bo. Nhm II: virus cha DNA si n. S sao chp xy ra trong nhn lin quan s to thnh qua trung gian si kp c xem nh l khun cho tng hp li DNA si n th h sau. Nhm III: virus cha RNA si kp. Nhng virus ny c b gene c chia on. Nhng on ny c phin m ring to ra cc monocistronic mRNA. Nhm IV: Virus cha RNA si n mch (+), c th chia nh thnh 2 nhm: + Virus vi polycistronic mRNA. RNA genome to ra mRNA, phn t ny dch m to sn phm l mt polyprotein, thng c phn ct to cc protein trng thnh. + Virus phin m phc tp. Cch dch m (nh Togavirus) hoc cc RNA ca subgenome (Tobamovirus) cn thit to RNA ca b gene. Nhm V: Virus cha RNA si n mch (-), genome ca virus ny c chia thnh 2 nhm: - Genome khng chia on (Mononegvirales). Bc u tin trong sao chp l phin m RNA si (-) ca genome nh RNA polymerase ph thuc RNA ca ht virus to ra monocistronic mRNA, c xem l khun cho sao chp genome. - Genome c chia on (Orthomyxoviridae). Sao chp xy ra trong nhn vi monocistronic mRNA cho mi gene ca virus c to ra nh enzyme transcriptase t genome y ca virus. Nhm VI: Virus cha mRNA si n mch (+) qua trung gian DNA. B gene ca retrovirus l mRNA mch (+) nhng dng lng bi. Chng khng trc tip to ra mRNA m phin m ngc to DNA. Nhm VII: DNA si i qua trung gian RNA. Virus nhm ny da vo enzyme phin m ngc, nhng khc vi retrovirus, qu trnh ny xy ra bn trong ht virus trong sut qu trnh trng thnh.
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Si RNA (-) virus b phn ct

5' C Tng hp mRNA 3' Ti bn 5' 3' 3' 5' 5'
Tai lieu chia se tai: wWw.SinhHoc.edu.vn Phn t duy nht

C C C Tng hp mRNA 5' si RNA (-) genome Ti bn 3' si (+) c chiu
di y
3' 5' 3'
si RNA (-) 5' genome
Si RNA (+) virus Flavi v picornaviruses

5' C Ti bn 3' 5' C 5' C 5' 3' 5' C
Alphaviruses
Ti bn
si RNA (+) genome (mRNA)
5' si (-) c chiu

di y
5' C
Tng hp mRNA si RNA (+) genome (mRNA)
Ambisence RNA virus

5'C RNA genome
RNA virus si i
si (+) 5' si (-) 3' Tng hp mRNA
C 5'
Tng hp mRNA
C 5' mRNA 3' 5' C 5' Anti Tng hp -genome RNA mRNA mRNA
3'
C 5'
3'
C 5'
Si (+) c chiu di y (mRNA) Dch m Ti bn si (+) 5' si (-) 3'
Protein
RNA genome
C 5'
Hnh 8.9 Sao chp RNA ca virus
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1. Cc virus ca vi khun - Bt u nhim
C 3 pha bt u cho xm nhim ca virus. - Sao chp v biu hin genome ca virus - Gii phng cc virion trng thnh t t bo b nhim Bacteriophage c thm vo nui cy vi khun ang sinh trng mnh v sau mt vi pht nui cy b gim, ngn cn tng tc gia cc ht phage v t bo. Ngay sau khi lm gim nui cy, c giai on khong 1015 pht khng pht hin thy cc ht phage, y l giai on che khut (eclipse period). iu ny xy ra mt thi gian sau khi nhim vo t bo, lin quan vi genome ca chng nh l iu kin trc tin cho sao chp. giai on ny khng c s nhim na v vy khng th pht hin nh vt m. Giai on mun l thi gian trc khi ht virus mi u tin xut hin v khong 20-25 pht cho hu ht cc bacteriophage. Khong 40 pht sau khi t bo b nhim, ng cong v s lng ht virus tng s v virus ngoi bo hp nhau thnh mt v lc ny, t bo b nhim lm tan v gii phng cc ht phage ngoi bo. Cc bacteriophage lm cht t bo ch gi l c (virulent) v chng sinh sn theo chu trnh tan Cc virus n ho (temperate virus) c th sinh sn m khng l cht t bo ch. Chng c hai kh nng sinh sn: chu trnh tan v chu trnh tim tan khng lm cht t bo ch. Chu trnh sng bt u khi phage gn vo b mt t bo E. coli v bm DNA vo trong gy nhim. DNA ca phage sau khi vo t bo to DNA vng trn v s tham gia vo mt trong hai chu trnh. DNA ca phage c th hoc tham gia vo chu trnh tim tan ca phageT4 hoc gn vo nhim sc th ca vi khun nh ti t hp im chuyn bit bc vo chu trnh tim tan. 2. Cc virus thc vt Hu ht virus thc vt c genome RNA, tuy nhin 2 nhm virus thc vt c nghin cu nhiu nht c cha genome DNA: Cauliflower mosaic virus (CaMV) v gemini virus. - Cc virus RNA Phn ln virus thc vt c b gene RNA si n mch (+) v nhiu dng c capsid hnh que, cc protein capsomer hnh xon.
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+ Tobacco mosaic virus (TMV)
Genome TMV l RNA si n. Genome ca chng m ho t nht 4 chui polypeptid. Protein 130 v 180 kDal c dch m trc tip t cng mt codon bt u trn RNA b gene. Hai protein khc, 30 kDal v protein v c dch m t on RNA. Protein 130 v 180 kDal lin quan vi sao chp virus, trong khi protein 30 kDal cn cho s di chuyn ca virus t t bo ny n t bo khc. V vy 3 loi protein ny cn cho s nhn ln ca virus trong ton b cy. - Cc virus DNA Virus thc vt c b gene DNA rt him, ch gm 2 nhm: + Cauliflower mosaic virus: CaMV c nghin cu nhiu nht trong nhm Caulimovirus. y l nhm virus dng cu, cha genome DNA vng trn, mch kp, kch thc khong 8 kb. Caulimovirus gy ra mt s bnh lm thit hi kinh t cy trng. Chng c ph vt ch hn ch, ch nhim cy 2 l mm. DNA ca CaMV c cu trc khng bnh thng, c 3 im gin on trn si kp, hai im trn mt si v mt im trn si cn li vi nhng vng trnh t overlap. Ngoi ra DNA CaMV c ribonucleotide gn vi u cui 5 ca im gin on. T cc nghin cu CaMV, Hull v Covey (1983), Pfeiffer v Hohn (1983) cho rng sao chp CaMV lin quan vi phin m ngc qua trung gian RNA ca b gene. Chu trnh sao chp ging vi retrovirus v hepatitis B virus. + Gemini virus: Gemini virus l nhm virus c ph xm nhim rng, c cy mt l mm v 2 l mm.Virus sc vn l ng (maiz streak virus MSV) l mt gemini virus ly nhim qua l, c truyn do cn trng. B gene ca geminivirus cha phn t DNA vng trn si n. Sao chp DNA virus c ngh l xy ra nh trung gian DNA v genome ca virus sao chp cho nhiu bn sao trong nhn ca nhng t bo tng sinh nhanh. Virus gy ra s c ch sinh trng v l c sc vng ca nhng cy ng b nhim. 3. Cc virus ng vt Chu trnh sao chp ca virus ng vt c nhiu im tng t vi cc virus khc vi nhiu bin dng ng k. Virus ng vt thng c promoter mnh, c th p dng cho biu hin gene. Trong nhiu trng hp, chng c kh nng sao chp genome ca chng vi s lng ln bn sao trong t bo.
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Mt s virus ng vt nh retrovirus gn DNA ca chng vo nhim sc th t bo ch nh l mt phn chu trnh sao chp ca chng. - Cc virus RNA nh retrovirus, paramyxo virus Retrovirus c ph vt ch rng gm chim, ng vt c v v nhng ng vt khc. S nhim ca retrovirus khng dn n lm cht t bo. Biu hin gene ca virus mnh nh promoter mnh. Retrovirus cha genome RNA. Ht virus cha 2 bn sao RNA. Mi genome RNA c nhiu tnh cht tng t vi mRNA eukaryote: c trnh t poly(A) khong 200 n v u mt 3 v cu trc m u 5. Virus xm nhim vo t bo km theo enzyme reverse transcriptase v intergrase. Enzyme reverse transcritase tham gia phn ng tng hp cDNA, dn n s hnh thnh bn sao DNA mch kp ca RNA virus, c gi l DNA provirus. DNA provirus c ng vng trn nh protein intergrase v c xen vo genome t bo ch. Thng ch c mt bn sao DNA provirus c gn vo trong mt t bo ch. im gn vo genome l ngu nhin. Retrovirus l mt tc nhn gy ung th. Hu ht chng c cu trc genome cha trnh t oncogene. Oncogene virus thng c to thnh t gene ca t bo v thng l kt qu ca s dung hp gene t bo vi gene ca virus. Kt qu l nhng virus gy ung th nh th b mt chc nng gene ca virus. Chng c th sao chp trong ly nhim hn hp vi mt helper virus cung cp chc nng b mt. - Cc virus DNA: SV40, Bovine papilloma virus (BPV) Ht virus SV40 cha DNA mch kp, vng trn, khong 5,2 kb c gn vi 4 phn t histon: H4, H2a, H2b v H3. SV40 c th tham gia vo hai kiu chu trnh sng ph thuc vo t bo ch. Trong t bo cho php virus xm nhim (permissive cell) thng l cc dng t bo n nh c ngun gc t kh chu Phi, s sao chp virus xy ra nh cc trng hp nhim bnh thng. Trong t bo khng cho php (non-permissive cell), thng l nhng dng t bo chut, khng c s nhim lm tan t bo v virus khng th sao chp ton b DNA ca chng. nhng t bo kh b nhim v lm tan do SV40, c th phn ra 3 giai on. Trong sut 8 gi u tin, ht virus khng v v DNA ca chng di chuyn n nhn t bo ch. 4 gi tip theo l pha sm (early phase), c s tng hp mRNA sm v protein sm v c s kch thch tng hp DNA ca t bo ch. Trong pha mun xy ra 36 gi tip theo, trong giai on ny c s tng hp DNA ca virus, mRNA mun v protein mun, lp rp virus v lm tan t bo.
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+ Bovine papilloma virus (BPV)
BPV gy nn bnh bu (wart) tru b. BPV c genome DNA si kp, vng trn khong 7,9 kb. 4. Cc virus gy ung th, HIV/AIDS Khong 15% ung th ngi c c ch hnh thnh lin quan vi virus. Chng c cc nhm sau : + DNA virus: h Apovavirus (Papilloma virus), h HepDNAavirus (Hepative-B virus), h Herpesvirus (Eptein-Barr virus) + RNA virus: h Retrovirus (HIV-1, virus AIDS) Cc virus gy ung th c th tc ng do xen on DNA ca chng vo b gene ch. Ngoi ra c th thc hin : + Hot ho b my sao chp DNA ca t bo ch. + Km hm tc ng ca cc tumour suppressor gene ch yu hot ho sao chp DNA Nh vy bng nhiu cch khc nhau cc virus khi xm nhp t bo c th lm t bo mt s kim sot bnh thng. AIDS l hi chng do virus lm suy gim min dch ngi (HIV). Ht virus l mt khi cu, b ngoi g gh, gm v bn ngoi, trong l cht nn protein bao quanh li c mt ct dng nn. Trong li c genome gm 2 si RNA ging nhau gn vi enzyme DNA polymerase l reverse transcriptase. Trong qu trnh nhim, virus HIV bm v nhim li ca n vo t bo h thng min dch ca ngi. Tip theo chng s dng enzyme reverse transcriptase sao RNA genome ca chng thnh phn t DNA si kp trong t bo cht ca t bo ch. Phn t xon kp ny chuyn n nhn, gn vo nhim sc th t bo ch nh mt enzyme khc. Khi gn vo nhim sc th ca t bo ch, genome ca virus. Mt khi gn vo nhim sc th ca t bo ch, genome ca virus c th thc hin mt trong 2 qu trnh. N c th trng dng b my tng hp protein ca t bo ch c th to ra hng trm ht virus mi sinh sn bng ny chi, tch khi mng t bo v i khi lm cht t bo ch. N cng c th tim tng trong nhim sc th ca t bo ch, ri sao chp v truyn genome virus sang 2 t bo mi khi t bo phn chia.
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Glycoprotein
Tai lieu chiabao tai: wWw.SinhHoc.edu.vn se Mng

Capsid HIV xm nhp vo t bo
T BO CH RNA virus Enzyme sao m ngc
Enzyme sao m ngc a. Cu trc ca HIV
Lai DNA-RNA RNA (2 si
phn bit)
DNA Protein virus
DNA NST
Provirus
RNA NHN
b. S sinh sn ca HIV
HIV mi
Hnh 8.10 Chu trnh sinh sn ca virus HIV
Ngoi ra sinh hc hin i cn pht hin ra hai dng sng c bit l cc viroid v prion - Viroid: l nhng phn t RNA rt nh (200-400 nucleotide), dng que c mc cu trc bc hai cao (Hnh 8.11). Chng khng c capsid v v bao (envelope) v ch cha mt phn t acid nucleic n. Viroid gn lin vi bnh thc vt. Viroid u tin c pht hin v nghin cu y nht l viroid ng thoi khoai ty (potato spindle tuber viroid-PSTVd). Viroid khng m ha cho bt k mt protein no v n c sao chp nh RNA polymerase ca t bo ch hoc c th nh mt sn phm ca mt gene RNA polymerase ph thuc RNA trong mt vi t bo eukaryote. Chi tit ca sao chp n nay ngi ta cha r, dng nh n xy ra nh c ch vng trn xoay c s ct (autocatalytic cleavage) v gn (self-ligation) to ra viroid trng thnh.
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Vng kt thc bn tri
Vng gy bnh
Vng trung tm c tnh bo th
Vng bin d
Vng kt thc bn phi
Hnh 8.11 Cc vng chc nng ca phn t RNA viroid
Gia cc viroid khc nhau c cc trnh t khc nhau, n c s dng trong phn loi chia viroid thnh ging (genera) v loi (species). Tuy nhin, tt c viroid u c c im chung l vng trung tm c tnh cht bo th lin quan vi sao chp ca chng (Hnh 8.12). Mt nhm cc viroid c kh nng to thnh cu trc u ba (hammerhead) lm cho chng c tnh cht enzyme ca mt ribozyme. Hot tnh ny c s dng ct cu trc nhiu n phn to ra trong qu trnh sao chp. Cc viroid khc s dng cc enzyme cha c bit trong t bo ch thc hin iu ny. Mt vi viroid gy bnh trm trng v gy cht thc vt ch. Cc viroid khc gm cc loi t khng c biu hin bnh bn ngoi n c triu chng bnh nh.
Hnh 8.12 Cu trc RNA viroid
- Prion: Mt nhm bnh ly nhim h thn kinh kinh nin, pht trin nhanh chng v gy cht c bit nh l bnh xp no ly nhim (Transmissible spongiform encephalopathics - TSE). Tc nhn ly nhim lin quan n TSE khng phi l acid nucleic (Tikvah Alper, 1967). Cc bnh TSE ngi nh l bnh Kuru v Creutzfeldt-Jacob c th gy nn do cc phn t protein gy nhim v Standley Prusiner (1982) gi chng l prion (proteinacious infectious particle). Bn cht ca prion l cha c chng minh mt cch chc chn. Chng l mt hin tng mi vt ra ngoi hiu bit thng thng. Tt c cc bnh prion u c bnh l ging nhau c bn, mc d gia chng c s khc bit c ngha nhng iu
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kin khc nhau. Cc bnh khc nhau c c trng bi s lng (deposition) ca cc protein bt thng trong cc m khc nhau nh thn, lch, gan hoc no ... S lng cc amyloid ny bao gm s tch lu cc protein khc nhau dng tm hoc dng cun ri to ra protein amyloid. Chng l kt qu t nhng sai hng ca b gene trong trao i cht do nhiu loi nhn t cha c bit.. Mc d c ch phn t lin quan vi s cht ca t bo l cha r rng, nhng tc ng gy ra xp no do to l m no c quan st thy di knh hin vi. Nhng l ny gy ra do s mt t bo thn kinh v gliosid. Php chn on xc nh TSE khng ch tin hnh trn lm sng m yu cu chng minh s lng protein prion (prp) bng nhum ho hc min nhim m no ngi sau khi cht.
Cu hi v Bi tp
1. Hy trnh by qu trnh ti t hp genome ca bacteriophage. 2. Genome ca vi khun v virus tng tc vt l theo cch no? 3. ngha ca vic phn tch cu trc locus rII ca phage T4. 4. Hy nu c im v chu trnh sng ca phage. 5. Virus thc vt c nhng nhm no? 6. Hy trnh by phng thc sao chp ca virus cha RNA si n. 7. c im chu trnh sinh sn ca virus HIV. 8. Hy nu tn cc dng sng ch c acid nucleic hoc ch c protein. 9. C bao nhiu m tan ca phage c to thnh trn mi trng nui cy t mt phage ring l ban u? 10. Bacteriophage c trt t cc gene l ABC att DEF. Hi trt t ca cc gene ny prophage nh th no?
Ti liu Tham kho

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
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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. Cann AJ. 2001. Priciple of molecular virolory. Academic Press. London, UK. Flint SJ, Enquist LW, Krug RM, Racaniello VR, Skalka AM. 2000. Principles of Virology. Molecular Biology, Pathogenesis, and Control. ASM Press, Washington DC. Printed in the United States of America. Harlt D.L., Jones E.W. 1998. Genetics - Principle and analysis. Jone and Bartlett Publshers, Toronto, Canada. Hartwell et al. 2003. Genetics: From genes to genomes, Second editor. The McGraw-Hill Companies. Old RW & Primrose SB. 1989. Principles of gene manipulation. Blackwell Scientific Publication. Stansfield W.D. 1991. Schaums outline of theory and problems of 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. Benjamine Cummings, San Francisco, United States of America.
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Chng 9
Tai lieu chia se tai: wWw.SinhHoc.edu.vn Di truyn hc Vi nm v Vi to
Mc tiu ca chng
Phn tch di truyn mt s vi to v vi nm, ch yu tp trung nghin cu cc c im ca vi nm, vi to nh tnh khng dung hp, phn tch b bn, phn tch di truyn trong chu trnh cn hu tnh, nhim sc th nhn to
S tit: 3 Ni dung I. i cng v nghin cu di truyn mt s vi to thng dng

Loi vi to c s dng sm nht v nghin cu di truyn chi tit hn c l Chlamydomonas reinhardii. u th ca i tng ny l c th tin hnh lai v phn tch b bn khng xp theo th t. cc loi ny, cc t bo n bi c th sinh sn v tnh mt thi gian di. Cc t bo n bi gm 2 loi: mt (+) v mt (-), t bo n bi ca mi loi khng kt hp vi nhau. S kt hp hai t bo khc kiu bt cp mt (+) vi mt (-) to ra hp t. Hp t qua gim phn cho t l phn ly ca mt gen l 2 t bo mt (+) : 2 t bo mt (-). Trong iu kin th nghim, c th nui cc t bo Chlamydomonas reinhardii nhn cc t bo ng nht (synchronous culture), khi thay i chu k 12 gi sng 12 gi ti u n. Theo di tng hp DNA cho thy DNA ca lc lp tng hp vo gi th 5-6 ngoi sng, cn DNA ca nhn tng hp khong gi th 16-18, sau chia t bo ng lot. Mt s t bin khng streptomycine c thu nhn v nhn thy mt s c s di truyn trong nhn, s khc c s di truyn ngoi nhn.
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Cp giao t
S to cp Dung hp t bo Tp hp li + Kt hp nhn v NST Hp t Hnh thnh cp (NH4+) Gim phn Ny chi (NH4+ hay nh sng) Pht trin hp t (NH4 hay nh sng) Hp t trng thnh T l 2:2 ca yl+ v ylT l 4:0 ca sm-r v sm-s yl+ yl+
+
Dung hp
Gim phn
yl-
yl-
sm-r sm-r
sm-r sm-r
Sn phm n bi sau gim phn
Hnh 9.1 Gen nhn (yl) phn ly 2:2 trong qu trnh to giao t cn gen ca lc lp (sm) phn ly theo t l 4:0
II. Phn tch di truyn vi nm

1. Tnh khng dung hp (incompatibility) vi nm Khi nim tnh khng dung hp nm c dng ch kh nng kt hp vi nhau gia cc dng nm trong sinh sn hu tnh. Cho n nay gn 450 loi nm c nghin cu v cc kiu khng dung hp. S khng dung hp c xc nh v mt di truyn. Theo kiu dung hp th nm c phn lm 2 loi: - ng tn (Homothallic) l khi c s kt hp vi nhau gia cc t bo (hay h si t-mycellium) ging nhau trong sinh sn hu tnh. V d, t bo a kt hp vi t bo a, hay vi to dng lng bi 2n tng ng aa hay . - D tn (Heterothallic) l kiu khi c s lai nhau gia 2 loi t bo khc nhau nh a vi to dng d hp t lng bi a. Cc nm d tn c th chia thnh: lng cc (bipolar) v t cc (tetrapolar). i din in hnh ca nm d tn lng cc (bipolar heterothallic) l nm men Saccharomyces cerevisiae. nm men, s hp bo (cytogamy) v
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hp nhn (karyogamy) ch xy ra gia cc t bo (hay nang bo t ascospora) c kiu bt cp (matting type) khc nhau nh a v v cc allele khc nhau ca locus MAT. Do c s tham gia ca 2 allele nn gi l lng cc. Nm mc vng bnh m Neurospora crassa cng thuc kiu khng dung hp ny. Nm rm (Volvariella volvacea) v nm m (Agaricus bisporus) cng thuc loi ny. Kiu d tn t cc (tetrapola heteropolic) c trng cho nhiu loi nm m Bacidiomycetes m i din l Schizophyllum communae. Nm bo ng (Pleurotus) v nm hng (Lentinus edodes) thuc kiu khng dung hp ny. S xc nh di truyn khng dung hp cc loi nm ny do 2 gen A v B. Mi gen c 2 allele hoc nhiu hn, thng l A1, A2 v B1, B2. S kt hp gia cc dng n bi ch to dng hu th c kiu gene A 1A2B1B2 tc bn nhn t khc nhau, do gi l t cc. S a dng ca cc chu trnh sng v cc kiu khng dung hp nm c nh hng n cc phng php phn tch di truyn. mt s nm sinh sn hu tnh thc hin trn c s d hp bo (heterogamy) nh Neurospora crassa. nhng loi khc trn c s ng hp bo (isogamy). Song song vi sinh sn hu tnh cn c chu trnh cn hu tnh hon ton hay khng hon ton ph thuc vo loi nm. Chu trnh sinh sn cn hu tnh l qu trnh kt hp v ti t hp gene din ra trong nguyn phn ch khng phi gim phn, khng c s th tinh nh sinh sn hu tnh. 2. Phn tch b bn v lp bn vi nm Nm men c nhiu c trng tr thnh m hnh l tng cho nghin cu di truyn eukaryote. Nm men l mt eukaryote n bo, chu k sng ch khong 90 pht, c th thu uc nm men vi s lng ln khi nui trn mi trng c. B gen ca nm men cha khong 12 megabase vi 6.000 gen phn b trn 16 nhim sc th. Nm men l eukaryote u tin c gii m b gen. Chu trnh sng ca nm men gm hai giai on c th chuyn i qua li. T bo c th tn ti c dng lng bi v c dng n bi. Trong c hai trng hp, t bo m to chi ging ht n. Nhng t bo lng bi ny c th tip tc sinh trng bng mc chi v c th tri qua gim phn to 4 bo t n bi (haploid) trong mt nang (ascus) c gi l tetrad. Bo t n bi (haploid spore) ca kiu kt cp khc nhau (a vi ) s qua
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th tinh to th lng bi. Nhng bo t ca kiu kt cp ging nhau s tip tc sinh trng bng ny chi. Nm men c xem l E. coli ca cc t bo eukaryote, c th s dng nm men phn tch t bin. T bo nm men n bi c gy t bin bng tia X, sau sng lc cc kiu hnh t bin trn mi trng nui cy. u tin nui cy t bo nm men trn mi trng giu dinh dng tt c cc t bo pht trin. a nui cy ny sau c nhn ln qua a sao chp cha mi trng chn lc hoc iu kin sinh trng c bit. Chng hn, cc t bin nhy cm nhit c th sinh trng trn cc a gc nhng li khng sinh trng trn cc a sao chp nhit gii hn. So snh cc khun lc a gc vi a sao chp s pht hin c nhng t bin nhy cm vi nhit .
Nang cha 4 bo t ti d hp
Ny chi
Dinh dng
Dinh dng
Ny chi
Hnh thnh bo t Vng i s.dng (n bi) Ny chi Vng i s.dng (n bi) Ny chi
Gim phn
Thiu nitrogen Kt hp hnh thnh hp t Vng i s.dng (n bi) Ny chi
Tai lieuHnh 9.2se tai: wWw.SinhHoc.edu.vn chia Chu trnh sng ca nm men.
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Lp nang khun (Ascomycetes) c c im l khi cc t bo lng bi phn chia gim nhim s to ra cc bo t nm trong mt v bao c gi l nang (ascus). Cc c th ny c cc c im thun li cho phn tch di truyn: Cc vi nm c th tn ti dng n bi, nn tt c cc gene c th biu hin trc tip thnh kiu hnh. Cc vi nm ny c th to ra s lng c th ln th h sau nn c th pht hin cc s kin di truyn him v c th c lng c tn s ti t hp mt cch chnh xc. T bo nm men c th sng dng sinh dng n bi hay d bi. Tn hiu chuyn t n bi sang d bi xut hin theo dng kt hp v tn hiu chuyn t d bi sang n bi l s gim phn trong qu trnh hnh thnh bo t.
T bo phn chia sau khi hnh thnh chromatid
Gim phn I Gim phn II Nguyn phn
Hnh 9.3 Mc vng bnh m (Neurospora crassa) l m hnh nghin cu phn li trong gim phn Trong chu trnh sng, ch c hp t l lng bi, s tri qua gim phn ngay sau khi c to thnh, to cc bo t n bi, bo t ny mm hnh thnh giai on cy. mt s loi cc b bn to thnh tri qua mt ln phn chia nguyn nhim na to ra tng cp gm hai bo t ging ht
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nhau. mc vng bnh m (N. crassa), cc bo t xp thng hng trong nang theo mt trt t xc nh lin quan trc tip n tin trnh ca gim phn (Hnh 9.3). Hu ht cc loi nm mc khc, sn phm ca gim phn khng sp xp theo mt trt t c bit trong nang nh mc vng bnh m. - Lp bn di truyn bng phn tch b bn i vi trng hp b bn khng theo th t: V d: khi lai cc t hp ca hai gene AB ab. S th tinh cho nhn lng bi AB/ab v n chia gim nhim ngay. Nu khng c trao i cho xy ra hoc trao i cho i xy ra trn cng hai chromatid th s c b bn: 2 AB : 2ab, gi l kiu i cha m (parental ditype PD). Nu trao i cho xy ra trn c bn chromatid ca mi cp nhim sc th kp, s c 2AB : 2aB, gi l b bn kiu i khng cha m (Nonparental ditype NPD) hay cn gi l kiu i ti t hp (Reconbinational ditypeRD) Trng hp to ra mi nang bn loi bo t c kiu gene khc nhau: 1AB : 1Ab : 1aB : 1ab c gi l kiu bn (tetratype) Phn tch b bn cho php xc nh hai gene lin kt. Khi hai gene khng lin kt th tn s b bn kiu i b m v kiu i khng b m bng nhau (PD = NPD). Ngc li khi hai gene lin kt, kiu PD c tn s ln hn kiu NPD. Tn s tng i ca cc kiu b bn khc nhau c s dng xc nh bn khong cch gia hai gene lin kt.
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Parent ditype
Nonparent ditype
Tetratype
PD NPD T
Hnh 9.4 Phn tch b bn 3. Phn tch di truyn trong chu trnh cn hu tnh (ti t hp trong nguyn phn) Nhiu loi nm c si dinh dng kt hp vi nhau, lm cho cc nhn n bi t cc dng cng chung trong t bo cht. Cc th d nhn (heterocaryon) c to nn c th tn ti lu di nh N. crassa. S to thnh cc th d nhn c s dng rng ri nghin cu s tng tc gia cc gene, gia cc allele v gia cc gene ca nhn vi t bo cht. Trong mt s trng hp, s so snh cc d hp t v d nhn cho thy s khc nhau trong tng tc gia cc allele, c l do:
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- T l s lng nhn v tng ng cc allele trong th d nhn c th khc nhau - Cc allele ca cc gene mt nhn khng c ngn cch nh gia cc th d nhn. Cc nhn th d nhn i khi hp nhau to nn on lng bi. Hn na trong qu trnh chia nguyn phn tip theo, nhn lng bi c th chu tc ng ca hai qu trnh: n bi ho hoc ti t hp nguyn phn. 3.1. S n bi ho (Haploidisation) S n bi ho c th xy ra ngu nhin hoc c gy to bi cht nfluorphenylalanin. Nu nh cc nhn trong nhiu nguyn phn b 1 nhim sc th (2n 1) th nhn lch bi va xut hin tr nn khng n nh v tip tc mt cc nhim sc th khc ca mt b n bi, cho n khi tr thnh nhn n bi (n) n nh. Trong qu trnh nhim sc th b mt c lp nhau, cc gene ca cng mt nhim sc th c s lin kt hon ton. Da vo c im ny c th xc lp s lin kt da vo gene nh du trn mi nhim sc th. 3.2. Ti t hp trong nguyn phn (Mitotic recombination) Ti t hp trong nguyn phn l hin tng thng gp nhiu sinh vt, khi xy ra trao i cho gia cc nhim sc th tng ng trong nguyn phn. Trong trng hp ny khong cch ca gene nh du xa tm ng nht, s ng hp t ho thng xy ra hn c (c coi l 100%) v s phn b cc gene c tnh theo cng thc: D = Nab/Nb x 100% D: khong cch ca gene n tm ng Nb - tng s cc dng phn li, ng hp t theo b. Nab - s cc dng phn li ng hp c a v b, nu nh b l gene nh du xa tm ng nht. Bn lin kt gene c xy dng bng ti t hp gim phn v ti t hp nguyn phn (trong chu trnh cn hu tnh) c th t gene xp ging nhau Aspergillus nidulans.
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III. Nm men nh l E. coli ca cc t bo eukaryote

1. Cc nhim sc th nm men nhn to (YAC)
xy dng nhim sc th nhn to c chc nng nh mt phn b gene ca t bo, m bo s phn chia ca nhim sc th cn c tm ng (centromere). Th hai, phn u mt ca nhim sc th thng di c gi nguyn vn khi a vo t bo, trnh c s phn gii ca nuclease nh on trnh t DNA lp li c bit v phc hp protein bao u nhim sc th l telomer. Cui cng, DNA phi sao chp trc khi t bo phn chia v vy nhim sc th nhn to sao chp phi c t nht mt im xut pht sao chp.
Plasmid a. AMP Ori 2 LEU2 b. Ori 1 - Sao chp t ng - Mi t bo c nhiu phin bn Ori 2 LEU2 ARS CEN AMP Ori 2 LEU2 - Sao chp t ng - Mi t bo c mt phin bn - Phn ly trong gim nhim nh l mt nhim sc th - Khng th sao chp t ng - im gn vo vng tng ng l LEU2 - Mi t bo c mt phin bn c im
c.
Hnh 9.5 Plasmid ca nm men a. YIp: khng cha ori v khng th sao chp t ng b. YEp: cha im ori 1 v sao chp t ng c. YCp: cha tm ng v phn ly trong qu trnh gim phn LEU2: gen nm men, Ori 1: xut pht sao chp ca plasmid nm men, Ori 2: xut pht sao chp ca vi khun, AMP: gen khng khng sinh ca vi khun
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Vo nhng nm 1980, cc nh di truyn hc phn t a ra 3 yu t cha kha cho mt nhim sc th: centromere, telomer v im xut pht sao chp v s dng vt liu t t bo nm men l plasmid cu to nhim sc th nm men nhn to. Cho n nay, eukaryote ch tm c mt loi plasmid duy nht l plasmid vng trn 2 m di khong 6300 cp base c nhiu trong t bo nm men Saccharomyces cerevisiae. S ci tin plasmid ny qua nhiu bc to thnh nhim sc th nhn to nm men, gi l YAC (yeast artificial chromosome), c cha cc trnh t nucleotide quan trng: ARS (autonomously replicating sequence): trnh t sao chp tng t ori plasmid. CEN (centromere): trnh t ca tm ng, m bo s chia i v i v 2 cc ca t bo nh tm ng. 2 TEL (telomere): hai trnh t duy tr hai u mt nhim sc th thng m khng b ct, vn sao chp v phn chia
Ch ct bng EcoRI
Hnh 9.6 NST nhn to ca nm men 2. Nhng hiu bit chia sechc ca cc nhim sc th ca nm men Tai lieu mi v t tai: wWw.SinhHoc.edu.vn 174
Nm men l c th eukaryote n bo, b my di truyn ca n ging vi t bo ca c th bc cao. Cc im xut pht sao chp, tm ng v telomer c xc nh l mt on DNA nh, t do. T bo nm men n bi c 16 nhim sc th trong nhn, xp thnh dy c chiu di khong 235.000 n hn 2 triu bp. Tt c c cu trc theo cng bn chi tit. Mi nhim sc th cha mt tm ng. Hai u nhim sc th cha on lp li di theo sau trnh t telomer ngn. Trn nhim sc th c cha nhiu im xut pht sao chp, cch nhau khong 30-40 kb. Nhim sc th nm men cng to thnh cc n v l cc nucleosome cha li histon gm H2A, H2B, H3 v H4. in di trn gel vi trng dao ng (pulse field gel electrophoresis), tch ra nhng nhim sc th nguyn vn v lp c karyotype phn t ca nhim sc th nm men. Da vo karyotype c th quan st c cc bin i ch yu trong cu trc nhim sc th. Qua karyotype cho thy, nhim sc th s I di khong 235 kb l nhim sc th nm men nh nht. Nhim sc th s XII ln nht vi kch thc khong 2060 3060 kb, s khc nhau v kch thc ca nhim sc th ny do s lng gen ca rRNA lp li vi s lng khc nhau, thng dao ng khong 100 200 bn sao nhng chng khc nhau. Trnh t DNA ca nm men c gii m 100% vo thng 4/1996.
a. on gn cui lp li Tm ng
im khi s sao chp
b.
NST
30 - 40 kb
on cui
Hnh 9.7 Nhim sc th nm men a. Cc thnh phn ca NST. Mi si cha 1 tm ng, nhiu im khi s sao chp, cc on gn cui lp li v on cui ca chui DNA. b. H gen ca NST nm men trn hnh nh in di.
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Bn di truyn ca nm men c xc nh bng phn tch b bn. Mt n v chc nng ca tn s ti t hp trong gim phn khong 4400 cM, trung bnh khong 3 kb/cM. Khong cch di truyn t l vi khong cch vt l. Bn di truyn ca nm men di khc thng so vi bn di truyn ca cc c th nm khc. V d: Neurospora crassa c cng hm lng DNA nh nm men nhng bn di truyn ch di khong 15% bn di truyn ca nm men. S lng gene m ho protein ca nm men t hn khong 6 10 ln s lng gene ca ngi. T khi chng trnh gii m genome nm men hon thnh vo nm 1996, khng th ni chnh xc c bao nhiu gene m ho cho protein nm men. S lng gene m ho protein ca nm men khong 6.000 6.500 gene nm men. 3. Nhng hiu bit mi v ti bn v phin m ca b gen nm men Nm men c th hon thnh mt chu trnh sao chp v phn chia khong 1,4 gi. Xut pht cho sao chp DNA ca nm men gm nhiu im ging vi oriC ca E. coli. l vng giu AT c tch ra khi c mt protein khi ng gn vo im k bn. Cc im xut pht sao chp di hng ngn n hng chc ngn nucleotide. Khc vi prokaryote, mi nhim sc th eukaryote c nhiu im xut pht sao chp qu trnh sao chp genome ca eukaryote c kch thc ln hn nhiu xy ra mt cch nhanh chng. C khong 400 im xut pht sao chp phn b trn ton b 16 nhim sc th ca nm men. S sao chp xy ra trc tip trn nhiu im xut pht sao chp. Si mch kp c to thnh mi im xut pht sao chp ko di v ni vi si kp c to thnh mt im khc. Khi sao chp trn 2 mch n hon thnh s to ra 2 phn t DNA con ging ht nhau. S tng hp DNA ch xy ra mt giai on trong chu trnh t bo, l pha S. nm nm men c 3 protein cn cho lp rp ca replisome. l phc hp DNA polymerase phi hp hot ng ch ba sao chp. Phc hp nhn bit im xut pht (Origin recognition complex ORC) s gn vo trnh t xut pht ca nm men nh DnaA protein ca E. coli. Nhng phc tng t c tm thy tt c cc eukaryote. S c mt ca ORC lm b sung thm 2 protein khc, Cdc6 v Cdt. C 2 protein ny v ORC lm kch hot helicase v nhng thnh phn khc ca replisome. S gn vo ca helicase c xem l s xc nhn (license) cho im xut pht, gip lp rp replisome v bt u tng hp DNA.
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Trong s cc gene m ho protein, intron ch c khong 4-5% tt c cc gene ca nm men (276 gene cha mt intron n v 7 gene cha 2 intron ring r), kch thc trung bnh ca intron khong 2000 nucleotide. Tn s thp ca intron nm men c l lin quan vi tn s thp ca cc gene gi (pseudogene) ging nh intron, ph bin eukaryote bc cao. Gene gi cha trnh t m ho, nhng v thiu intron v promoter phin m nn trnh t m ho khng c biu hin. Gene m ho protein khng ch l nhng dng gene chc nng. Genome ca nm men cha s ln gen to ra RNA khng m ho, bao gm cc gene lp li m ho cho rRNA, 274 gene ca tRNA, trong c 80 gene cha nhm intron c bit, 71 RNA nhn nh (smRNA) tham gia chc nng ch bin rRNA, 5 smRNA tham gia ch bin intron, mt vi RNA cha bit chc nng v 3 RNA nh l cc tiu n v chc nng ca enzyme Rnase, endoribonuclease v telomer. 4. Nhng hiu bit mi v ADN ty th ca nm men DNA ty th nm men di 4 ln hn DNA ty th ca ngi v nhng ng vt khc. Hai yu t trn DNA ty th nm men c cho l c kch thc ln hn so vi cc i tng khc: trnh t gia cc gen (intergenic) v intron. Trnh t di, giu A-T ca vng m spacer tch bit vi cc gene ca mtDNA. Hu ht DNA ca spacer u c dch m v mt s trong chng c duy tr trn mRNA nh u 5 v 3 ko di, khng dch m. Yu t th hai l intron, chim khong 25% genome ty th nm men v n c xem l to ra s khc nhau v kch thc gia mt DNA ca nm men v ngi.
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RNA ti t hp ln
RNA ti t hp nh
Hnh 9.8 DNA ty th nm men
Cu hi v Bi tp
1. Hy trnh by qu trnh sinh sn v tnh ca to Chlamydomonas reihardii. 2. Hy cho bit cc kiu dung hp vi nm. 3. S xc nh gii tnh vi nm nh th no? Cho v d. 4. Cc kiu b bn no c to ra do dng nm men lng bi c kiu gene AB/ab, nu A v B lin kt hon ton? 5. Trong 100 chu trnh gim nhim ca Neurospora theo cch bnh thng c bao nhiu bo t c to thnh? 6. ngha ca phn tch b bn trong nghin cu di truyn. 7. Hy trnh by cu to nhim sc th nhn to ca nm men v ng dng ca chng. 8. Mt chng khng khng sinh ca nm men c phn lp, cho kt cp vi mt chng hoang di nhy cm vi khng sinh to th lng bi. Sau khi sinh sn mt vi th h, chng c kch thch sinh bo t. Kt qu thu c b bn nguyn phn cha 8 bo t gm 4 bo t khng khng sinh v 4 bo t nhy cm khng sinh. Hy kt lun v s di truyn ca tnh khng khng sinh.
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Ti liu Tham kho
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 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. Cann AJ. 2001. Priciple of molecular virolory. Academic Press. London, UK. Flint SJ, Enquist LW, Krug RM, Racaniello VR, Skalka AM. 2000. Principles of Virology. Molecular Biology, Pathogenesis, and Control. ASM Press, Washington DC. Printed in the United States of America. Harlt D.L., Jones E.W. 1998. Genetics - Principle and analysis. Jone and Bartlett Publshers, Toronto, Canada. Hartwell et al. 2003. Genetics: From genes to genomes, Second editor. The McGraw-Hill Companies. Old RW & Primrose SB. 1989. Principles of gene manipulation. Blackwell Scientific Publication. Stansfield W.D. 1991. Schaums outline of theory and problems of 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. Benjamine Cummings, San Francisco, United States of America.
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Chng 10
Tai lieu chia se tai: wWw.SinhHoc.edu.vn Di truyn T bo cht
Mc tiu ca chng
Gii thiu DNA ca cc bo quan ty th, lp th v s di truyn do cc gene trong t bo cht quy inh.
S tit: 3 Ni dung I. S di truyn t bo cht
Hnh 10.1 Cu trc t bo
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. Tai hai b m c thnh phn nguyn liu di truyn trong t bo cht Nu lieu chia se tai: wWw.SinhHoc.edu.vn 180
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 chlorophylle.
Hnh 10.2 Th khm m l
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 hoa 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 Tai lieu chia se tai: wWw.SinhHoc.edu.vn 181
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.
Hnh 10.3 S di truyn cc gene lp th
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 lai l m v 30% l xanh lc.
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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 ti 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 Tai lieu chia se tai: wWw.SinhHoc.edu.vn 183
thy c s di truyn ngoi nhn t bo v mt s c s di truyn theo mt cha m. 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.
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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.
Hnh 10.4 S di truyn cc gen ca ty th trong hnh thnh khun lc petite
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
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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 ti 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 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, 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...
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Hnh 10.5 S th nghim chng minh s di truyn theo h m ca bt th c
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 ST T 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 phn) hng tt tt tt (ht
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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 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.
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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 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.
Hnh 10.6 Hiu qu dng m ln chiu xon v c
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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 lp th v ty 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 streptomycine 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: sm-r mt+ sm-s mt- tt c th h con u sm-r vi t l 1 mt+ : 1 mt-. sm-s mt+ sm-r mt- tt c th h con u sm-s vi t l 1 mt+ : 1 mtNh vy y khi c s hon i cha m trong lai, th h con u c kiu hnh streptomycine ca mt+. S truyn th tnh trng ny c gi l s
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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.
Hnh 10.7 Bn vng trn ca cpDNA Chlamydomonas
Hnh 10.8 Bn DNA chloroplast ca Marchantia polymorpha IRA v IRB l nhng trnh t o ngc (theo K. Umesono v H. Ozeki, 1987)
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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). 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 erySspiS erySspiR eryRspiS 63 b bn 48 b bn 7 b bn 1 b bn
Cc kiu gene erySspiR 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, ant R 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 restriction enzyme: cc restriction enzyme l cng c hu hiu mi phn tch di truyn. N c s dng khng Tai lieu chia se tai: wWw.SinhHoc.edu.vn 192
nhng phn tch mtDNA ca nm men, m c mtDNA ca bt k sinh vt no min chit tch v tinh sch c DNA di truyn. * 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 - mtDNA ca ngi rt t d tha
Hnh10.9 Bn mtDNA ca ngi (Theo Larson N.G v Clayton D.A, 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
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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 Eukaryota nhng ging vi b my sinh tng hp protein ca Prokaryota. 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. 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.
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2. Cc b gene ty th (mtDNA)
Bo quan ti th c tt c cc t bo ca Eukaryote. B gene ca ti th c k hiu l mtDNA (Mitochodrial DNA). mtDNA m ha cho s tng hp nhiu thnh phn ca ti th nh h thng 2 loi rRNA, 22-25 loi tRNA v nhiu loi protein c trong thnh phn mng bn trong ti th. Trong khi , phn ln protein ca ribosom ca ti th th do cc gene trong nhn xc nh. B gene ca ti 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 ti th. Nh vy, vic nghin cu cc gene ca ti 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 n 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.
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7. HyTai lieu chiat bin petite nm men. phn bit cc loi se tai: wWw.SinhHoc.edu.vn 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 nucleotid ca 1 ty thr trong thi gian 1.500 n 3.000 nm. DNA ty th ngi c khong 16.500 nucleotid. Hi t l bin i ca 1 nucleotid trong 106 nm l bao nhiu?
Ti liu Tham kho

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. 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 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, 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, United States of America.
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Chng 11
Tai lieu chia se tai: wWw.SinhHoc.edu.vn S iu ha biu hin ca gene
Mc tiu ca chng
Gii thiu v cc qu trnh iu ha trong c th sinh vt. S iu ha ca gen c thc hin cc mc khc nhau. Hot ng theo kiu operon c trng cho iu ha Prokaryote. Eukaryote c cc c ch iu ha phc tp.
S tit: 3 Ni dung 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
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Hnh 11.1 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.
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- 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.
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 dng tnh (Hnh 11.1). Trong h thng iu ha m tnh (Hnh 11.1A) 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 11.1B), 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.
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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 11.2). 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 gene (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 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. 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 ngn cn phin m.
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Hnh 11.2. 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
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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.
Hnh 11.3 Cu trc ca cAMP
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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 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.
Tng hp ca mRNA lac khng Repressor khng Phc hp cAMP-CRP
C Phin m khng
Hnh 11.4 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 11.4). 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
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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
Hnh 11.5 iu ha ca operon trp E. coli A. Protein aporepressor khng bm c vo operator, phin m xy ra. 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.
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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 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 5 giai on, 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 gene. 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 to tryptophan. (Hnh 11.5.). 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. 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
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base xy ra s kt thc c gi 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: - 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 11.6).
Hnh 11.6 A. S phin m ca leader trp B. Chi tit cu trc ca 2 codon trp vng 1-2
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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 11.6B). 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 11.7). Khi vng leader c phin m, s dch m leader polypeptid cng bt u. V c 2 codon trptophan 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 11.7B). 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.
trp codons
B
Kt thc phin m
S kt cp trong RNA nng thp ca tryptophan
RNA polymerase
Phin m tip tc
S kt cp trong mRNA
S kt cp trong RNA nng cao ca tryptophan
Hnh 11.7 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
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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 operon leucine, isoleucine, phenylalanine, histidine) cng c iu ha nh attenuator vi chc nng to ra vng kt cp bin i bn 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. 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 gene (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. prokaryote, mt vi protein c mt trn nhim sc th b gp np, cn li hu ht DNA trn. 208
- 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
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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 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 (diffrentiation) 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.
Hnh 11.8 S t chc cc gene in hnh Eukaryote bc cao
Qua s hnh 11.8 cho thy nhiu yu t di truyn c tm thy trong gene ca eukaryote in hnh. Phc hp phin m bm vo promotor
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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 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-boxbinding 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 factor) = 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 histon 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
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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.
Hnh 11.9 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
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 loi t bo, cng
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mt bn phin m s cp (primary transcript) c tng hp, nhng c hai qu trnh ch bin khc nhau (Hnh 11.9). 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.
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 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

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.
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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.
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Chng 12.
t bin gene, ti t hp v cc yu t di truyn di ng

Mc tiu ca chng
Gii thiu cc kiu t bin gen, c ch pht sinh v hu qu ca chng. C ch sa cha cc t bin lm gim t l t bin, duy tr tnh n nh ca vt liu di truyn. Ngoi t bin gene, yu t di truyn vn ng cng l nhn t lm tng tn s t bin
S tit: 3 Ni dung 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 nhin (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
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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 delection) Cc t bin ny c th pht sinh do nh hng ca mi trng nh nh hng ca cc tc nhn gy t bin. 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 baz 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
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Tai lieupurine) se tai: wWw.SinhHoc.edu.vn chia (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 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).
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Tai lieu chia12.1 t bin im mc phn t se tai: wWw.SinhHoc.edu.vn Bng

Kiu t bin Kt qu v v d Purine c thay th bng mt purine khc, pyrimidine c thay th bng mt pyrimidine khc: A.T G.C, G.C A.T, C.G T.A, T.A C.G Transversion Purrin c thay th bng mt pyrimidine hoc mt pyrimidine c thay th bng mt purine: A.T C.G, A.T T.A, G.CT.A, G.CC.G T.AG.C, T.A A.T, C.G A.T, C.GG.C 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 DNA
Transition
mc protein
Codon c bit m ho cho cng mt acid amin: AGG CGG Arg Arg Codon to thnh m ho cho amino acid khc M ho cho acid amin c cng bn cht ho hc: AAA AGA Lys (kim) Arg (kim)
Synonymous mutation Missense mutation Loi bo th
Loi khng bo th
M ho cho amino acid khc v bn cht ho hc: UUU UCU Phenylalanin k nc Serine Phn cc CAG UAG Gln Stop
Nonsense mutation Frameshift mutation
Codon kt thc chui: Thm vo mt cp base:
AAG ACT CCT AAG AGC TCC T... Mt mt cp base: AAG ACT CCT AAA CTC CT...
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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.
Gen 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 12.1 Hu qu ca t bin im trong gene. Codon 1-4 nm trong vng m ha ca gene
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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 12.1). 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 12.1). 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. 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.
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2. C ch gy t bin im
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. 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 12.2), 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. 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 -CH 3 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 Tai lieu chia se tai: wWw.SinhHoc.edu.vn 221
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.
Hnh 12.2 Chng minh mt vi kt cp nhm c th xy ra do kt qu ca s thay i 1 tautomer thnh 1 tautomer khc
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)
Hnh 12.3 S kt cp nhm chuyn bit do t bin cm ng alkyl ho
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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 12.3). 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 nitrogen base 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 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. * 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: depurination v deamination, trong depurination 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
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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. 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 12.4). Qu trnh sao chp to ra t bin ng hon chuyn C thnh T. 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.
Hnh 12.4 Deamination ca Cytosine (a) v 5-methylcytosine
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.
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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

1. C ch sa sai sinh hc T bo sng c hng lot h thng sai hng DNA theo nhiu cch 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. 1.1. Quang phc hot (photoreactivation) hay sa sai nh nh sng (light repair) 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 12.5).
Hnh 12.5 S to thnh v s loi b dimer thymine
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1.2. 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: + Ct cc base (base excision repair) 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 Nglycosilic 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 12.6). 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 exinuclease (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.
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Hnh 12.6 Sa sai bng ct b nucleotide
+ c sa i vi cc base bt cp sai C ch c sa i vi cc base bt cp sai (proofreading for base-pair 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)
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Hnh 12.7 M hnh b gy si i nh trao i cho
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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 12.7): 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. 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 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,
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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.
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Bng 12.2. Mt vi trnh t xen vo v kch thc ca chng

Trnh t xen vo IS1 IS2 S bn sao trong E. coli 5-8 bn sao trn nhim sc th 5 bn sao trn nhim sc th, 1 bn sao trn plasmid IS3 5 bn sao trn nhim sc th, 2 bn sao trn plasmid IS4 IS5 1-2 bn sao trn nhim sc th, Cha bit 1400 1250 16-18 Ngn 1400 32-38 Chiu di (bp) 768 1327

on lp li o ngc (bp) 18-23 32-41
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:
Hnh 12.8 c trng v cu trc ca transposon hn hp (composite transposon) v transsposon n gin (simple transposon)
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Transposon hn hp (composite transposon) cha nhiu gene nm gia 2 trnh t IS gn nhau, c hng ngc nhau to ra tnh 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. 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 12.8). 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 12.9). 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)
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Hnh 12.9. S nhn i on trnh t DNA ngn im xen vo (insertion site)
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.
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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 bn sao ca yu t xen on gi l Ty1 genome ca nm men. 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 12.10)
Hnh 12.10 S chuyn v nh retrotransposition
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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. 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. 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 McClintok 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
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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.. 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.
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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 n 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. 7. Cc trnh t o ngc c vai tr g trong transposition? 8. Cho mt chui trnh t nucleotid 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 nucleotid do kt cp nhm nh sau: 5' AGCTGCCTT 3'
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Tai lieu chia 5' (mch khun) se tai: wWw.SinhHoc.edu.vn 3' ACGATGGAA
mRNA Hy cho bit acid amin no s c tm thy codon c nucleotid b thay i nh trn? 10. bp, tn s t bin ca locus R (mu cy) rt co: 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

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 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, 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. Benjamine Cummings, San Francisco, United States of America.
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Chng 13
Tai lieu chia se tai: wWw.SinhHoc.edu.vn t bin nhim sc th
Mc tiu ca chng
Gii thiu cac loai t bin cu truc nhim sc th, bn cht ca vt cht di truyn l DNA, thnh phn, cu trc ca phn t DNA, dng DNA khc nhau trong t bo.
S tit: 3 Ni dung
I. t bin cu truc nhim sc th

Cc t bin cu trc NST hay cn gi l sai hnh NST (chromosome structure) hay cu trc li NST (chromosome rearrangement) c pht hin bng phng php t bo hc. Cc t bin loi ny thc cht l sp xp li cc gen hoc gim hay tng liu lng gen.
Hnh 13.1 C ch pht sinh mt s t bin cu trc nhim st th
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Hinh 13.2 Cac dang t bin nhim sc th
Cc sai hnh NST c th chia thnh 2 loi: Bn trong NST: mt on, o on, tng on Gia cc NST: chuyn on 1. Bin i cu trc trn mt NST: 1.1. S pht sinh cc t bin cu trc trn NST Sai hnh NST lin quan n s t on ca NST. C khi 1 NST b t ra qu 2 on v sau c ni li nhng thng khng gi cu trc c. iu dn n nhiu kiu t bin cu trc NST khc nhau. Cc on vng trn khng tm ng thng b mt i trong phn bo. C th xy ra trng hp 2 on c tm ng ni nhau, khi phn bo s b ko cng ra 2 u thnh cu chromatid v sau b t ra khng u to ra mt ci mt on v ci kia tng on. 1.2. Mt on S thiu mt on NST gm 2 loi: mt on (deletion) gia NST v mt nh (deficiency). on NST b mt nu nh c th mang 1 gen hoc mt phn gen. Trong trng hp ny hiu qu kiu hnh c th ging nh xut hin alen t bin locus . Cc mt on khng c t bin nghch, bi
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v on NST b mt kh ngu nhin c gn tr li do t bin. Nh mt on c th phn bit vi t bin gen. S mt mt on di NST thng gy cht do s mt cn bng di truyn ca b gen.
Hnh 13.3 S m t hin tng "gi tri"
S mt nh ca on NST mang gen tri A cho php alen ln a c biu hin kiu hnh. Khi mt sinh vt d hp t (Aa), s mt on c A th alen ln a trn NST kia c biu hin kiu hnh. Hin tng ny gi l "gi tri" (Pseudodominant), tht ra locus tng ng trng thi bn d hp t (Hemizygote). Tip hp gim phn I khi c mt on S mt on c th d hp c th pht hin k trc ca gim phn I khi cc NST tng ng bt cp. Nu c mt on s thy xut hin mt vng trn do khng c on NST tng ng. V d v t bin mt on ngi: khi mt vai ngn ca NST s 5, karyotype 46,XY,del(5p) dn n hi chng mo ku (Cri du chat). Tr s sinh b hi chng ny c ting khc nh mo ku. Bnh c gp vi tn s 1/50.000 tr, biu hin chm tr, u nh v him khi sng c ti lc trng thnh. S mt mt phn vai di ca NST s 22 (c gi l NST Philadelphia, ly tn thnh ph ni pht hin ra u tin). N c tm thy t bo ty xng (cng vi cc t bo c NST bnh thng) ca 90%
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nhng ngi bnh bch huyt myelocyt kinh nin (mt dng ung th). Thng on b mt c chuyn n mt NST di hn (thng l NST s 9). 1.3. Lp on (tng on - Duplication) Cc lp on NST c th tng ln bng nhiu cch khc nhau. Ni chung s lp on khng gy hu qu nng n nh mt on, thm ch mt s lp on c li cho tin ha l to vt liu di truyn mi. Lp on c th cnh nhau, xa nhau trn cng mt NST hay vo cc NST khc. Nh lp on c th nghin cu nh hng ca s lng v v tr khc mc bnh thng ca mt on NST hay gen. Kiu hnh ca lp on c khi tri, c khi ln hay trung gian hoc c tc ng tch ly. Trng hp in hnh v lp on l t bin tri mt thi Bar (B) nm trn NST X ca Drosophila. Trng hp tng mt on, d hp t +/Bar th mt b hn bnh thng mt t, hp cnh nn c dng ko di. Rui ng hp BB c mt nh hn. Nu lp on i, tng hn bnh thng 2 on s l t bin Bar kp, c kiu hnh mt nh hn na nn gi l "thi kp". S on lp li c th n 7 on thnh "siu Bar" mt nh nht. Gen mt thi B c tc ng gia tng theo chiu gim kch thc mt, s on lp cng nhiu, mt cng b. C trng hp khc, lp on tc ng theo hng ngc li, s on cng tng th kiu hnh cng tr v bnh thng hn. Cc kiu gen hoang di, Bar v Bar kp tng ng vi cc on trn NST khng l S tng on Bar nh mt nhn t tri v mt di truyn. Khi nui cc rui Bar ng hp t BB nhn thy cc rui hoang di xut hin rui con vi tn s1/1.600 v cc rui Bar kp cng xut hin vi tn s tng t. S xut hin cc kiu hnh bt thng c th gii thch bng trao i cho khng cn bng khi tip hp gim nhim I. 1.4. o on (Inversion) o on xy ra lc on trong t i quay 1800 ri c ni li.
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Tai s trnhchia se tai: ca on NST l 1-2-3-4-5-6, hai ch b lieu t bnh thng wWw.SinhHoc.edu.vn Gi
t xy ra vng 2-3 v 5-6 v oanh b t ni o ngc. Nh vy NST c on 1-2-5-4-3-6
Hnh 13.4 Ngun gc ca o on
o on mang tm ng (Pericentric inversion) Tm ng nm bn trong on b o. Trong gim nhim I cc NST tng ng khi tip hp s to vng trn kp. Nu trao i cho xy ra gia 2 si NST n trong vng o on th 2 chromatid ca mi NST thng c chiu di khng cn bng nhau. Trong trng hp ny, mt na sn phm ca gim phn va c lp on li c mt on nn mt sc sng. Na khc ca cc giao t (khng c trao i cho) c sc sng bnh thng gm 1/4 c on vi trnh t gen bnh thng v 1/4 c o on. V d d hp t c o on xy ra trao i cho vng 3-4. Cc NST ti t hp c on trng on en u lm giao t mt sc sng v c gen tha, c gen thiu. + NST en trng bn tri c cc gen (6-3-4-56) (2 gen 6, thiu gen 12) + NST en trng bn phi c cc gen (1-2-5-4-3-2-1) (2 gen 1-2, li thiu gen 6)
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Hnh 13.5 Trao i cho xy ra on o
Hinh 13.6 Cp nhim sc th di hp do ao oan hinh thanh vong trong giam phn (a) S ca s tao vong (b) Anh chup hin vi in t qua trinh tao vong
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o on khng mang tm ng (Paracentric inversion)
Hinh 13.7. Trao i cheo xay ra oan bi ao
Hinh 13.8 San phm giam phn do kt qua trao i cheo n vong ao oan khng mang tm ng
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Tai lieu nm ngoi tai: wWw.SinhHoc.edu.vn trong chia se on b o. Trao i cho xy ra bn Tm ng

on o to NST hng tm (c 2 tm ng - dcntric chromosome) v trong k sau I s to nn cu ni, ni 2 cc t bo. Cu ni s b t bt k ch no to ra cc on khng cn bng cha lp on hoc mt on. V d trng hp xy ra trao i cho gia 4-5 Trao i cho xy ra on khng mang tm ng Cc NST khng c trao i cho (trng c hay en c) to giao t c sc sng, s khc to giao t mt sc sng v khng cn bng di truyn. on khng tm ng (acentric fragment) to ra s b mt v khng di chuyn c v cc. Mt na sn phm ca gim phn s mt sc sng v do tha v thiu gen, 1/4 c sc sng bnh thng v 1/4 c sc sng vi NST c o on. Bin i cu trc gia cc NST 1.5. Chuyn on (Translocation) Chuyn on l s trao i cc on gia cc NST khng tng ng. Trao i on c th xy ra trong i NST tng ng (thng khc chc nng) nh gia X v Y hoc gia cc NST khc i. S chuyn on thun nghch (reciprocal) xy ra do s tao i cc on gia 2 NST khng tng ng. Trong gim phn, cc NST c chuyn on tip hp vi nhau to nn hnh cho. Tip theo khi cc NST y nhau v cc cc, s c 2 trng hp: + Bn NST vo cui k trc I y nhau to nn vng trn. S phn ly trong trng hp ny s to nn cc giao t khng sc sng v mang mt s NST c d hoc thiu gen. V d: 1-4-3-4 thiu 2 v 1-2-2-3 thiu 4. + S hnh thnh s 8 do y cho nhau gia cc NST. Trong trng hp ny cc giao t c to nn c sc sng v c cn bng gen (mi giao t u c 1-2-3-4). Hai trng hp trn xy ra vi xc sut nh nhau nn cc dng c chuyn on thng na bt dcc (50% giao t cht). Tiu chun th hai pht hin cc chuyn on l c s thay i nhm lin kt gen. Mt s gen ca mt nhm lin kt gen c th chuyn sang nhm lin kt gen khc. Ngoi cc h qu di truyn trn, chuyn on c th gy hiu qu v tr
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(position effect). Cc gen khi di ch c th c biu hin khc, v d t vng ng nhim sc (euchromatin) chuyn sang vng d nhim sc (heterochromatin) t c hot tnh hn.
Hinh 13.9 Qua trinh giam phn xay ra th di hp chuyn oan
S hnh thnh chuyn on v s tip hp ca chng trong gim phn I * Nhim sc th u (Isochromosome) Cc NST c hai vai di khng u nhau c th chuyn thnh NST u vi 2 vai bng nhau v chiu di v tng ng vi nhau v mt di truyn nh s phn chia tm ng khc thng vung gc vi s tch tm ng bnh thng. NST X tm mt ca Drosophila c th chuyn thnh dng"X dnh" do s phn chia tm ng theo chiu vung gc vi bnh thng. Do s phn chia khc thng , 2 chromatid thay v phn li v 2 cu li dnh nhau, c on b mt.
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* Chuyn on Robertson (Robertsonian translocation)
Mt chuyn on c bit c gi l Robertson. y l trng hp hnh thnh NST tm gia do s ni li ca 2 NST. Chuyn on thun nghch c thc hin gia 2 NST tm u A v B, khi A b t pha di tm ng to vai di mt tm ng, cn B b t u mt ngn trn tm ng, 2 on ni nhau to NST tm u mang tm ng ca B. on c tm ng A vi vai ngn ni vi on ngn ca B hnh thnh NST con c tm ng A. NST con mi c nhiu chtss d nhim sc khng quan trng nn thng mt i. Chuyn on Robertson c hu qu lm gim s lng NST.
Hinh 13.10 Chuyn oan Roberson
S hnh thnh NST tm gia do s ni li ca 2 NST tm u (chuyn on Robertson) Ngi c 46 NST, cc vn ngi (hc tinh tinh, kh t, i i) c 48 NST. NST th hai ca ngi gm hai on ging 2 NST khc nhau ca cc vn ngi. Rt c th t t tin chung, mt chuyn on Robertson to nn loi ngi do s ni li ca 2 NST khc nhau, lm gim s lng cn 46 thay v 48 nh cc loi vn ngi.
II. t bin s lng NST.

a bi th (polyploidy): hiu theo ngha rng l s thay i s lng NST. S thay i s lng NST c nhiu kiu: a bi nguyn (euploidy), a bi lai (alloploidy) v a bi lch (aneuploidy) 1. a bi nguyn
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Taitng nguyn lnse tai: wWw.SinhHoc.edu.vn a bi lieu chia b NST n bi ca mt loi, c gi l S

th nguyn hay a bi th thun. y l a bi hiu theo ngha hp, nu c c th 2n NST th dng 3n, 4n, 5n ... l cc dng a bi th. - Th n bi (Monoploid): mt s sinh vt Eukaryote bc thpnh vi nm, vi to c nhn dn bi. Cc c th n bi sinh vt bc cao thng t hn v c sc sng km hn dng lng bi bnh thng. Cc thc vt n bi c tm thy nhng thng bt thi. Mt s t ng vt tn ti dng on bi. Mt ngoi l ng lu l ong c v ong v v. - Th tam bi (Triploid): tam bi NST (3n) c th c to nn do s kt hp gia cc giao t n bi vi giao t lng bi. B NST on bi th ba ca th tam nhim thng phn b vo cc t bo sinh dc vi nhiu loi t hp khc nhau, to nn cc giao t mt cn bng di truyn. Cc th tam bi c bt th cao nn trong thin nhin, chng thng dng sinh sn v tnh nh cy chui. - Th t bi (Tetraploid): t bi NST (4n) c th xut hin trong cc t bo c th do s tng i s NST ca t bo soma. S tng i s NST c th xy ra nh tc ng ca alkaloid colchicine vo t bo hoc do s hp nht ca cc giao t 2n. Trong c th lng bi, t bo mt s m chuyn bit tr thnh a bi. V d mt s t bo gan ca ngi l th a bi, ni nh ca ht nhiu loi thc vt l th tam bi.
Hinh 13.11 Th lng bi (phia trai) va th t bi (phia phai) cua nho
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2. a bi th lai: cn gi l th d bi a bi th lai c c khi c 2 b NST ca 2 loi khc nhau cng ng chung trong mt t bo (2nA + 2nB).
Hnh 13.12 Th a bi lai la m
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Hinh 13.13 Th a bi lai tao thanh khi lai gia hai loai Raphanus vi Brassica
3. a bi lch hay a nhim S thay i s lng NST ch lin quan n mt cp hoc mt s cp NST c gi l a bi th lch. Cc dng a bi th lch: + Th n nhim hay th mt (2n - 1) + Th tam nhim hay th ba (2n + 1) + Th t nhim hay th bn (2n + 2) + Th tam nhim kp (2n + 1 + 1) + Th v nhim hay th khng (2n - 2)
Hinh 13.14 C ch hinh thanh cac giao t tha hoc thiu nhim sc th do s khng chia ly cua nhim sc th trong giam phn
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Cc th a bi lch ngi:
ngi nhiu hi chng di truyn do cc th a bi lch lm thay i s lng cp NST gii tnh, a n cc dng: XXX (siu n), XXY (Klinefelter), OX (Turner), OY (cht) + Hi chng Turner do Henry Turner m t u tin ngi n mt mt NST X (OX), c cng thc 2n - 1 = 45. Hi chng c nhiu biu hin c trng nh ln (chiu cao < 1,5 m), c quan sinh dc km pht trin (khng dy th), km thng minh ...
Hnh 13.15 c im hi chng Turner (XO)
+ Hi chng Klinefelter do Henry Klinefelter m t nhng ngi nm d 1 NST X (XXY), cng thc 2n + 1 = 47. Hi chng c nhng biu hin c trng nh bt th, ngn tay, chn di, pht trin ngc, c tnh n v suy gim tr tu.
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Tai lieu chia (XXX)_ do d mt NST X, b gen 2n + 1 = 47, se tai: wWw.SinhHoc.edu.vn + Ngi siu n
thoi ha, suy gim tr tu. + Hi chng Down do Langdon Down pht hin, thng l tam nhim cp NST s 21 ca ngi. T l xut hin khong 1/600 tr s sinh. Ngi bnh c mt s biu hin c trng nh: thoi ha tr tu, mt ging mt ngi Mng c. C mi lin h thun gia s tr sinh ra mc bnh Down v tui ca cc b m. T l l 1/500 cc b m 20 - 30 tui, 1/300 cc b m 40-45 tui v 1/60 cc b m ln hn 45 tui. Tui cha hu nh khng nh hng. ngi cc n nhim t thy hn, c l do mang nhiu gen ln nguy him, nn trng thi bn hp t kh sng.
Hnh 13.16 c im hi chng Clinefelter (XXY)
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Hinh 13.16 Ngun gc Hi chng Down
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Hnh 13.17 c im hi chng Down
III. t bin gy to hay cm ng

1. Tc ng gy t bin ca bc x ion ha Tia X, cc tia phng x , , , cc neutron v c tia t ngoi u l cc tc nhn gy t bin. Tr tia t ngoi c kh nng xuyn thu yu nn ch tc ng ln cc sinh vt n bo v giao t, cc tia khc u c tc dng gy t bin ln tt c cc dng sinh vt. Tc dng gy t bin ca phng x c 2 c im: - Khng c ngng tc dng, tc khng c liu v hi - S lng t bin t l thun vi liu lng phng x, khng ph thuc cng v thi gian chiu x 1.1. Bc x ion ha nh sng nhn thy ch l mt phn rt nh ca ph sng in t. Sng c bc sng cng ngn th cha nng lng cng ln v kh nng xuyn thu cng mnh. So vi nh sng nhn thy (bc sng khong 10-4 m), cc tia X, tia , tia v tr c bc sng t 1 nm v ngn hn, c gi l bc x ion ha. Cc bc x ny c to ra nh cc my chiu tia X, proton, neutron v c pht ra t cc ngun phng x nh radium, cobalt 60, ... to cc tia anpha, beta v gamma 1.2. nh hng ca liu lng (dose) v cng bc x (radiation intensity) Cc th nghim sau nm 1927 vi bc x nng lng cao cho thy cc t bin gy to (t bin cm ng) ph thuc rt ln vo liu lng, liu cng ln tn s t bin cng cao. Khi liu lng qu cao, s ph thuc c phc tp hn, c th do nhiu t bo b cht. im ng lu , nhiu nghin cu cho thy cc bc x ion ha c hiu qu gy t bin tt c cc sinh vt v khng c liu lng ngng, c ngha l d liu lng thp vn c kh nng gy t bin. 2. Tc ng ca tia t ngoi
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Tait ngoi c bc sng di (10 -10 cm) nn kh to ion, c l lieu chia se tai: wWw.SinhHoc.edu.vn Tia
-5 -6
ch tc ng n nhng cht hp thu n trc tip. Trong t bo cc cht hu c mch vng ch yu nh purin v pyrimidin hp thu trc tip tia t ngoi. Mi lin quan cht ch gia tia t ngoi v cc cu phn ADN c chng minh. ADN hp thu tia t ngoi mnh nht bc sng 2537 , y chnh l bc sng lm tng tn s t bin ht phn cy bp. Di tc dng ca tia t ngoi, cytosine gn thm phn t nc vo lin kt C=C ca mch vng v thymine b t lin kt C=C mch vng ni 2 phn t thnh dimer thymine. 3. Cc tc nhn gy t bin ha cht C nhiu ha cht gy bin d di truyn, n nay tm ra nhng ha cht cho hiu qu t bin cao hn phng x. Cc ha cht gy t bin c c im l ch c th gy hiu qu t bin i vi mt s t i tng. Cc tc nhn gy t bin ha hc c th chia thnh cc nhm sau: Nhm 1: Cc cht c ch tng hp baz nit trong cu trc ADN nh cofein, ethyl uretan ... Nhm 2: cc cht ng ng vi baz nit nh cofein, 5-bromuracil, cc cht ny gn ging vi baz nit nn ADN gn nhm khi tng hp. Nhm 3: Cc cht alkyl ha lm t mch ADN nh ethyl methanesulfonate (EMS), methyl methanesulfonate (MMS), ethylene imine (EI) ... Nhm 4: Cc cht khc nh cht oxy ha - kh nh HNO2, hydroxygenlamine (H2NOH). Nhm 5: Cc cht chm vo ADN gm proflavin, cht mu acridin. Tt c tc nhn gy t bin u l tc nhn gy ung th, nhng cc tc nhn gy ung th khng phi u gy t bin. Hin nay nhiu tc nhn gy t bin c s dng trong chn ging nhm tng ngun bin d.
Cu hi v Bi tp
!. Bn cht v hu ca ca t gy v ni li ca nhim sc th. 2. Hu qu ca o on.
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3. Cc hnh dng quan st c trong gim nhim ca ng hp chuyn on. 4. Hu qu ca trao i cho n qu trnh hnh thnh b bn th d hp chuyn on l g? 5. M t s kin di truyn dn n s hnh thnh ngi nam XYY. 6. S khng phn ly ca nhim sc th gii tnh xy ra ngi n trong ln gim phn th hai to ra nhng loi trng no? 7. Gii thch s tng hu th th lai khc loi khi c s nhn i s lng nhim sc th ca chng.
Ti liu Tham kho

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 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, 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. Benjamine Cummings, San Francisco, United States of America.
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Bai Giang Di Truyen - Truong Thi Bich Phuong

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Bn cht ca vt cht di truyn

S tit: 6 Ni dung I. DNA l vt cht di truyn

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Tai lieu chia se tai: wWw.SinhHoc.edu.vn u - Tt c cc t bo dinh dng ca bt k mt loi sinh vt no

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Hnh 1.1 Th nghim bin np chut

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Hnh 1.2 Vt cht di truyn ca phage l DNA

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Hinh 1.3 S xm nhp DNA cua virus vao vi khun

II. Thnh phn v cu to ha hc ca acid nucleic

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Tai lieu chia se tai: wWw.SinhHoc.edu.vn - ng desoxyribose (DNA ), ribose ( RNA)

Trong nucleotide, base purin s gn vi C1 ca ng N9. Nu l pyrimidin th s gn vi C1 ca ng N3. C5 ca ng gn vi nhm phosphate.

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Hnh 1.5 S bt cp b sung ca cc base ca hai mch n

Trn c s cc nghin cu ca mnh, Chargaff (1951) a ra kt lun: + S lng A = T, G = C

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Hnh 1.6. Mi lin kt hydro gia A-T v G-C

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Hnh 1.7 Chui xon kp DNA

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Hnh 1.9 Cc dng thng, vng trn v xiu xon ca DNA

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Hnh 1.11 S tho xon DNA trong t bo vi khun

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Hnh 1.12 rRNA cu to nn ribosom

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Hnh 1.13 Cu trc ca tRNA

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