DNA Fingerprinting: A Review of the Controversy Author(s): Kathryn Roeder Reviewed work(s): Source: Statistical Science, Vol. 9, No.

2 (May, 1994), pp. 222-247 Published by: Institute of Mathematical Statistics Stable URL: http://www.jstor.org/stable/2246327 . Accessed: 13/03/2012 11:54
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Statistical Science 1994, Vol. 9, No, 2, 222-278

A DNA Fingerprinting: Review of the Controversy

Roeder Kathryn
have used genetic material(DNA) as evAbstract. Forensicscientists idence in criminalcases such as rape and murdersince the middleof of scientist's interpretation the evidence, the last decade. The forensic whenit involves especially has however, been subjectto somecriticism, in relevantareas ofpopulation genetics the issues (including statistical method sumof These issues includethe appropriate realmofstatistics). of error, independence eventsin a data subjectto measurement marizing of of characterization heterogeneity populations; or DNA pattern profile; reference to databases;and probamethods develop sampling appropriate reference of underuncertainty appropriate of evaluation evidence bilistic themaccessible to the theseissues,with goalofmaking database. I review is mostcases, community. thesisin thisarticle that,for My thestatistical amongindividualsobviatesconcern the tremendous geneticvariability of minor violations modeling assumptions. arisingfrom forensic population inference, Key wordsand phrases: DNA profiling, hetpopulation legal inference, equilibrium, Hardy-Weinberg genetics, erogeneity.
1. INTRODUCTION

thathavebeen techniques molecular used todescribe to scientists draw inferences by employed forensic at found crime materials and fluids other from bodily of scenes.The culpability a suspectis based,in part, to of on the similarity his DNA profile thatobtained at the scene ofthe crime. Berry(1991) introduced aspectsofthistopictoreaders someofthestatistical a ofStatisticalScience. In his articlehe presented of for newmethod assessingtheweight theevidence used to thismethod thosecurrently in and compared surthe courts. He also alluded to the controversy the the rounding subjectat thattime.In thisarticle withemwill of history thecontroversy be reviewed, features the data and of phasis on the confounding issues. statistical thepertinent occurred One ofthe earliestuses ofthistechnique during 1987 in Narborough,England (Shapiro, boy 1991). A seventeen-year-old was accusedofthe rape and murderoftwo girls,one in 1983 and the evidenceand his own in other 1987. Circumstantial indicatedthat he couldhave been previoushistory
Kathryn Roeder is Associate Professorof Statistics Box 208290, Yale Station, New at Yale University, Haven, Connecticut08520.
222

or DNA fingerprinting DNA profiling are terms

he Duringhis confession requesteda the murderer. of the bloodtest. By coincidence, laboratory noted Alec Jeffreys locatedwithin was molecular biologist methods pio6 milesofthevillage.Usingmolecular Wilsonand Thein(1985a, b), the neeredbyJeffreys, to suspect'sDNA was compared the spermsamples It thatboth on girls found thevictims. was concluded but wererapedbythe same individual, the boywas nottheperpetrator. can any maSuch DNA profiles be obtainedfrom terial that containsnucleatedcells: blood,semen, consists skin,hair rootsand so on. A DNA profile of a set of measurements discreterandomvariof ables, measuredwitherror.The randomvariables in each parent.Typioccur pairs,oneinherited from variables different pairsofrandom callythree five to if are measured.Forensic scientists declarea match to the profiles from two samples are considered be similar.Two samplesfrom same inthe sufficiently while error, dividualdiffer due to measurement only match. rarely different individuals samplesfrom If the samples fromthe suspect and the crime then the case does not go to trial unless criterion, the nonmatch immaterialin light of othereviis thereis a possibility false exdence. Although of this has not been the focusofcurrent declusions, bate. The controversy arises when the samplesdo
scene (evidentiarysample) do not meet the match

DNA FINGERPRINTING:A REVIEW OF THE CONTROVERSY

223

matchand some measure ofthe weightofthis evtheyare to idence is presented thejury. Typically of withan estimateofthe probability obpresented selected from randomly a profile taininga matching selectedpopuindividualfromsome appropriately population. This prolation, called the reference is fileprobability usually obtainedby multiplying for probability each comthe estimatedmatching ponent of the profile-thatis, by assumingindethe procomposing pendence of the observations of file. The estimatesof the probability matching are of foreach component the profile based on the thathave been of distribution profiles individuals of testinglaboratories.Samples by collected forensic are available foreach of the major ethnicgroups (races). were ignited The firstflamesof the controversy by the claim that therewere likelyto be grossvio(Lander, of lationsofthe assumption independence 1989; Cohen,1990). Subsequentstudiesofthe data by numerousauthorsrefutedthese initial claims 1990,199la; Chakraborty (Devlin,Rischand Roeder, and and Kidd, 1991; Chakraborty Jin, 1992; Weir, subdid 1992a,b),yetthecontroversy notcompletely side. concerned apthe key Another pointofcontention population(Weir propriatechoice of the reference and Evett, 1992; Lewontin,1993), as well as the populaadequacy of the samples of the reference stratitions. These databases do not constitute of fiedrandomsamples ofthe populations interest, but ratherare convenience samples(Geisser,1992). It has been arguedthat individualstend to marry religionand ethnicgroup withintheirown region, the general populationconsists and consequently of of subpopulations individualswithradicallydifleads to ferent probabilities.The argument profile rare profiles the conclusionthat some apparently in of be might common the context the propersub(Lewontinand Hartl, 1991). This arpopulation as gumentseems incompatible, manyauthorshave that profile probabilinoted,with the observation across majorethnic substantially not differ ties do even 1992a,b) and differ (Evett,1992a; Weir, groups withinan ethnicgroup less across subpopulations (Devlin and Risch 1992b;Devlin,Rischand Roeder, 1994). CounA study by sponsored theNationalResearch to examinethese issues, and precil (NRC, 1992) has to sumably quell thecontroversy, insteadfanned from thosewho genthe flames,drawingcriticism scientists' the forensic interpretation erallysupport the endorsed ofDNA evidence:yetthe NRC report of use of DNA profiling.Indeed a flurry forensic the NRC report articleshave appeared critiquing (Budowle and Monson, 1992; Cohen, 1992; Weir, 1992c,1993;Balazs, 1993;Devlin,Rischand Roeder,

1993a; Evett,Scranageand Pinchin,1993; Morton, Collinsand Balazs, 1993). Although manyofthe arguments forth the put by criticsof current methodsof evaluatingDNA evidence are theoretically correct, conclusions my are thatthe data do not support theirclaims. The concernaboutbothindependence the components of of theprofile thechoiceofreference and population are based on the assumption extreme of populationheterogeneity. Such extreme heterogeneity could only occurif individualswithina population(say, Caucasians) tend to marryotherindividualsfrom the same subpopulation (say, Irish, Italian, German, etc.) and these subpopulations have verydifferent profile probabilities; population geneticists woulddescribe situation extreme the as population substructure.Thereis littledoubtthatsomepopulation heterogeneity exists,although is notextreme the it for major ethnicgroupsconstituting U.S. populathe tion. Moreover, because thereis such a tremendous amountofvariability amongDNA profiles within a this subpopulation, heterogeneity oflittlepractiis in cal import mostcases. Claimstothecontrary, supdeviations modelassumptions, of ported apparent by have been based on incorrect analyses ofthe data, and hypothetical conjectures grossviolations of have notbeen supported empirical by evidence. In Section2 the data are described, and a simand the asple probability modelforDNA profiles sociated measurement errorsis presented. From theprobability model, methods summarizing the for of in are weight the evidence first developed Section 2 and expandedin Section6. Due to measurement a consists continuous of measurements error, profile ofdiscrete characters.A discrete model probability will be the focusof this articlebecause the methin ods currently use discretize the data. Methods it the forsummarizing data without discretizing are discussedin Section6. In Section 3 the genetic model (heterogeneity thatis mostcommonly assumed among populations) is to be thebasis for violations independence preof Hetand are sented, testsofindependence reviewed. is erogeneity amongpopulations also the reasonfor and aboutthechoiceofreference concern population the qualityofthe existing nonrandom samples.The reference to appropriate population evaluatetheevidencefora givencrimeis discussedin Section4. that allow forvarious levels of Statisticalmethods relatednessbetweenthe suspect and donorof the in evidentiary sample are also presented Section4. This discussioncoverscorrections that accountfor The population heterogeneity. adequacyofstandard is reference populations discussedin Section5. In Section7, issues surrounding some open questions are outlined. Finally, Section8, I contrast conin my clusionswiththosedrawnbytheNRC panel.

224

K. ROEDER

ANDTHE 2. DNA PROFILES: THE DATA EVIDENCE of A VNTR (variablenumber tandemrepeats)loby favored forenpresently cus, the geneticmarker locationof the genome is sic scientists, a specific is wherea coresequenceofnucleotides repeatedin and White,1980; times(Wyman tandemnumerous a Baird et al., 1986). DNA from VNTR locus oftwo in differ the generally randomly chosenindividuals numberofthese repeats,and hencein length. For are the eachlocus (location), data onVNTRlength obFirst, techniques. tainedbya sequenceofmolecular piecesusinga restriction theDNA is cutintosmaller thatcutsoutside(usually)theVNTRregion. enzyme are Next,fragments separatedbysize usinggel elecinto are The trophoresis. fragments thendenatured A ontoa membrane. rasinglestrandsand blotted dioactiveprobe,designedto attach to the core seis quence (the repeatingsegment), applied. When the film, radioactive the gel is exposedto an X-ray of sites appear as darkbands (Figure1). The length the is from distance the each DNA fragment inferred markers DNA has traveledon the gel. The genetic discussedare designedto yielda pair offragments each parent)at each locus. from (one inherited obtainedat a Considerthe pair ofmeasurements of givenlocus. Because ofthe large number alleles in of typesorlengths DNA) segregating the (distinct (two mostindividualsare heterozygous population, alleles at the locus) and generatebands of distinct two distinct lengths(Figure la). A singleband is at sometimes generated a locus (Figurelb); single(two banded patternsmay3bedue to homozygosity in copies of the same allele), to difficulties distinof guishingfragments similarlengthsor to an allele too small to be measured. See Devlin, Risch and Roeder (1990) and Devlin and Risch (1992a) Thompson forstatisticalanalysis and Steinberger, demonstration and Hartmann(1993) formolecular ofthesephenomena. the modelfor This section describes independence DNA profilesand reviewsthe calculationswhich to the presented summarize weightofthe evidence a jury. In Section 2.1 a modelis presentedfora can be obsimplercase in whichthe DNA profile error.The weightof servedwithoutmeasurement in of the evidenceis summarized the form a likeerroris lihoodratio. In Section2.2 measurement the introduced.Withmeasurement error, discrete set to is DNA profile transformed a continuous of to randomvariables. In an effort mimicthe methods developedfordiscretedata, a methodwas deconfor veloped,called match/binning, discretizing in is This method presented tinuousDNA profiles. Section2.4 reviewssomeofthe Section2.3. Finally, conmade bytheNRC committee recommendations

~-

~~~
(a)

I~~

(b)
are thefirst and secondlanes (columns) each autoradiograph on lanes thesuspect and evidentiary samples;thethirdand fourth In lane,the third are victim autoradiograph's samples. thesecond or twobandsblurred together coalesced. of of FIG. 1. Schematic autoradiographs twoloci (top,bottom):

laid out in this the calculations cerning probability section. 2.1 A Probability ModelforDiscreteData a individual A multilocusgenotype9 for particular eachof from consists unordered of pairsoffragments Lloci:
9 = {(A1,A2)e), = 1,... ,L}.

At each locus,Ai is a discrete variablethat random

takes on values, (alleles) {a(k), k = 1,.. .,m} with

on probabilities {y(k),k = 1,. ., m} thatdepend fand thatA1 is indethepopulation interest. of Provided pendentofA2 (Hardy-Weinbergequilibrium, herethe of afterH-W),the probability observing single-

DNA FINGERPRINTING:A REVIEW OF THE CONTROVERSY

225

{a(i), a(j)} can be calculatedas locus genotype Pr ( a(i)) a(j)l

(1)

f i 22y(i),y(j),/lj(heterozygotes),
-y'(i)2,

i =j (homozygotes).

two hybetween competing is objective todistinguish potheses: different from Ho: the sampleswereobtained individuals; sampleswere H1: the suspectand evidentiary the same individual. from obtained hypotheof Noticethatneither thesecomplementary ses containsan evaluationofguilt. In fact,formuguilt and innocenceare misleadlations involving even a ing: like dermalfingerprints,DNA profile, if unique, can onlyplace the suspect'sDNA at the crimescene. was thedonor UnderH1, becausethesame person sample,Pr(98= for boththe suspectand evidentiary when9s = 9e.Let us use 9 to itiesis onlyofinterest and genotype let Pr(9) denote denotethis matching the genotype of theprobability observing multilocus a population 9 in a randomdrawfrom hypothetical sample. This ofpotentialdonorsofthe evidentiary Unas population. is population known thereference der Ho, assumingthat the suspectand evidentiary from reference the drawn samplesare independently population, Pr(98 = 9e = 9) = Pr(9)2 Under these for the modelassumptions, evidence a crimecan be ratio: likelihood in summarized thefollowing
_

that obtained fromthe evidentiarysample

are the genotypes indepenprovided Furthermore, thenthemuldentacrossloci(linkageequilibrium), by can probability be obtained multilocusgenotype of acrossloci. The assumption independence tiplying whichwillbe discussed is a keypointofcontention, in further Section3. Assumethe geneticevidenceconsistsofthe multhe suspectand 95 tilocusgenotype obtainedfrom

9e. The

9e)= 1. Clearly,the cailculationofgenotypeprobabil-

to this point,it suffices note that all of the major possesslargedatabasesthatare laboratories testing populations.These sampleshave used as reference from menandwomen the for beenobtained, example, cases (see Section5.2). paternity testedin disputed is crimethe objective to choose For any particular of a database that is representative the genotypes in thatwe wouldexpectto find thepool ofpotential sample. For example,if donorsofthe evidentiary and the on a crimeoccurred a Navajo reservation was the of indicate perpetrator particulars thecrime would population Navajo, thena suitablereference sampleofNavajos. be a random it It has also been arguedthat frequently is not reasonableto assume that the suspectand evidenthe tiarysamplesare randomdrawsfrom reference underHo. For suchcases the modelforpopulation, mulation can be expandedto allow the evidentiary closely sampleand suspectsampleto be drawnfrom a or relatedindividuals individualsfrom clusterin thepopulation. = 1/Z2Z Pr(9) is preSuppose 2R = 106;typically as sentedto thejuryand interpreted theprobability drawfrom population. the ofobserving in a random 9 becausethevalue can Thispresentation be confusing be largerthanthenumber off9Zmight considerably of donors theevidenofpeoplein theset ofpotential is interpretation not tiarysample. The appropriate ratio: the at as a probability all, but as a likelihood is timesmorelikely have arisen to evidence a million by ifthecrime wereleft thedefendant scenematerial than if it were leftby some unrelatedperson. Anthe otherway to interpret data is via culprit-based on sampling. Let us condition the suspect'sgenotype, UnderH1, if9, = 9e = 9, thenthelikelihood 9g. ofobserving is 1; whileunderHo, the evidentiary 9 a sampleis obtainedas a randomdrawfrom hypothe thetical reference (excluding suspect) population a genotype of and thelikelihood observing matching is Pr(9): 1/Z2Z = Pr(9e I 9,,H0) = Pr(9), provided of donorsofthe evto do withthe number potential for identiary sample. If one wereto correct a finite perpetrators sample,thena small pool ofpotential if of increasesthe probability H1. Moreover, DNA were unique, then Pr(9) = 0 forany-sized profiles
referencepopulation, and Z9Z= oo.
?JR Multiplying by the priorodds ofH1 (assessed evidenceapartfrom on thebasis ofall thepertinent odds that the the DNA profile) yieldsthe posterior was measuredtwice, same individual
Se =

9,

9. Once again, this argument has nothing

Pr(9s,9e

H1)
_

?/R (2)
)

Pr (98s9e Ho) (Pr()xl

= {Pr(9)2

-Pr(9)'

9s ~~~~~f 9e

=9,

O,

if 9s 9e.

assumptions is Thiscalculation based onmodeling of thefocus somedebate.Theseissues thathavebeen of 4. in willbe discussed Section The choice reference At the mostcontroversial. populationis probably

(3)

odds(Hl)

Pr(Hl),GR.

was of oddsin the courts The presentation posterior againstby by (1991) and cautioned arguedfor Berry

226

K. ROEDER

Kaye (1991), who notes that outsideof civil suits, of Bayesianmethods havenotgainedmuch a foothold of in thecourts (see also Geisser, 1990). Fora review thelegal issues see Kaye (1988, 1991,1993).
2.2 A ProbabilityModel forContinuous Data

With conventional geneticmarkers(e.g., blood techniques groups,serumproteins), laboratory the are accurateenoughthat observations usually can alleles and (2) is presented be classified distinct to as for theweight the evidence H1. of a of Although VNTR allele can be thought as a catby egorical random variable,distinguished thenumit coresequences, is usuber oftandemly repeating of measureally thought as a discretequantitative of ment, defined itslength.Observations a pairof by measuring VNTR alleles are obtainedby indirectly thelengths a pairofalleles,usinggelelectrophoreof sis and autoradiography. VNTR's,becausethere For m is an enormous number alleles(typically > 100), of error makesit evena smallamount measurement of the into impossible directly to classify fragments alleles (Balazs et al., 1989); thatis, the unobservable are which discrete random pairoffragments (A1,A2), observyielding variables,are measuredwitherror, of able pairsofmeasurements alleles(X1,X2)at locus ? fora randomly chosenindividual:
(4 X1 = A1 + e1,
X2

a)
CD

::: ........./

a)

Sorter Alele
FIG.2. Aportion the of two-dimensional ofallelepairs(grid) space two with measurement relative error bottom) different for loci(top, totheallelespacing:thebivariate normal distribution measureof ment error a givenallelepair is superimposed thespaceof on for possiblesingle-locus Notetheincreased correlation in genotypes. allelepairsofsimilarsize.

A2 + 62,

a?), where ai = c x a(j). From experimental N(01 data, thenormality assumption appearsreasonable. and The value ofc is determined experimentally is known be laboratory to dependent (Devlin,Rischand Evettand Pinchin,1992). In Roeder,1991b; Berry, in the laboratories involved DNA testing, however, as thestandarderror is ofthesamemagnitude the cj difference betweenadjacentalleles; la(j) - a(j - 1)1. A2) the assumedto WVhile alleles(A1, arecommonly the causes be independent, molecularmethodology errors 62) to be correthe pairs ofmeasurement (E1, is which a function lated(Figure2). Thiscorrelation, can ofthe allele sizes and percent difference, be esof timatedfrom repeatedmeasurements the same function be decan the alleles. In brief, correlation that it A1 scribed follows: is 1.0 for = A2,ensuring as X1 = X2 (a homozygote always appears as a single and scienband on an autoradiograph, the forensic for tistrecords same measurement bothalleles); the but the correlation decreasesas IAi - A21increases, pairsthan thisdecreaseis slower larger for fragment forsmallerfragment pairs. [See Devlin,Rischand

A = a(j), it is commonly assumed that e is distributed

errors. ranThe are wheree1ande2 themeasurement of domerror is a function the allele size A. Given E

Roeder(1992) for moredetails.] Given(A1,,A2)= (a(i), a(j)), (Xl, X2) are assumed a to follow bivariatenormaldistribution withmean .mined themean. The corresponding by evaldensity uated at (x1, will be denotedby qi$(x1,x2). (Note x2) thatwhenA1 = A2, the distribution to degenerates a univariate Let density.) -y(i, denotetheprobabilj) thatthemarginal disj) -y(i, is givenin (1). It follows tribution (X1,X2) is thatofa normalmixture of with density
(5)
f(x1, x2)
= i<j

(a(i), a(j))

and variance-covariance matrix deter-

ityofsampling the genotype{a(i), a(j)};

under H-W,

7 (i, j)

ij(Xl, X2).

Because fragments visualized on an autoraare the bands have substantial diograph, corresponding width. This introduces complication A1 and A2 a if are verysimilarbut notidenticalin length.In this case, the bands may be indistinguishable because they blurtogether onlyone length - (xl +x2)/2 and z

DNA FINGERPRINTING:A REVIEW OF THE CONTROVERSY 6 of The probability this eventis a function ofthe t mean z and the difference = Ix1 - x21/2 ofthe al8(t,z)can be lele sizes. The coalescenceprobability the from data (Devlin,Rischand Roeder, estimated 1990). Coalescencewill not be discussedin detail to reader is referred Devlin, here. The interested Rischand Roeder(1990, 1991a, 1992). the Figure3 illustrates estimateofthe allele distribution {y(k), k = 1,..., m} fortwo loci commonly laboratories. (These allele distriused by forensic Corporation's Lifecodes from butionsare estimated Caucasian database; Lifecodesis an independent expotestinglaboratory.See Section6 forfurther used to obtainthe estimate.) sitionon the methods of Due to innate properties these two VNTR loci (Devlin,Risch and Roeder,1991b),the distribution with substantial on the top (D17S79) is estimated on (D2S44) whilethe estimator thebottom accuracy, variance.NoticethatD17S79 is not has substantial it although possesses about especiallyinformative: 53 alleles with y(k)> 0, fourofthese alleles make up about 60% of the probability.D2S44 is much it moreinformative: possess about 172 alleles with the and none ofthemdominates distribu-y(k) 0, > do the Furthermore, estimateddistributions tion. (race)(Devlin group by substantially ethnic notdiffer and Risch,1992b). ratioforcontinuous The idea ofusinga likelihood in of theweight evidence a to measurements assess was (1977). by proposed Lindley forensic setting first for reviewofmethods summaa In thisarticle, brief the discretizing data is rizingthe evidencewithout reviewof in presented Section6. For an extensive for information used to summarize genetic methods and cases,see Devlin(1993). bothpaternity criminal Methods 2.3 Match/Binning determineif 9e is observed. This phenomenon is called coalescence.

227

D17S79
cmJ
0 0

a)

_D

aI)

2nd 2 l t
00

(t

tpbD2S44

a)
0-

Alleles
estimates theD17S79 locus(top) FIG. 3. Thealleledistribution of the and theD2S44 locus(bottom): probabilities 98 allelesfor of axis D17S79 and 329 forD2S44 are estimated. The horizontal is units. thenumber repeating of

we variables, first random To apply(2) to discrete

=

in popthis genotype the reference ityofobserving of ulation. There is no obviousextension this simVNTR data. Because for ple method the continuous have forensicscientistsand the legal community withdiscrete markers, genetic decadesofexperience the that mimicked theycreateda method however, discrete approach. random To apply analogues of (2) to continuous thatclasa to it variables, is necessary construct rule of as sifiesa pair ofprofiles potentialobservations or not (an exclusion). (a the same genotype match) of the Whena matchis declared, probability observcalledbina method ing a matchis calculatedusing are binning ning. These methods knownas match/ because ofthe twostagesoftheprocedure. methods To illustratean approachused in the courts(prior

9,; if so, we calculate the probabil-

used the to the NRC report) us consider method let If Corporation. the DNA ofthe suspect byLifecodes similar, and evidentiary samplesappear sufficiently speakthe samplesare declareda match. Roughly are ing, if any fragments separatedby morethan threestandarddeviations (SD) ofthe measurement 1T2 theprofiles declarednonmatching, = 0 are error, and the suspectis excludedas a possible donorof because the meathe evidentiary sample. However, errorsare knownto have positivecorresurement exercisesomejudgment the experts lations, forensic near misses in theirdeclarations, declaring possibly as matches(whichmay or may not be acceptedby the court)and rulingout apparentmatchesdue to error.(The term of unlikely patterns measurement a is misnomer; match "match" actuallya convenient to is actuallya failure exclude. On rare occasionsa to locusis declared be inconclusive.) to is Because the standarderror proportional the comparesband lengthofthe allele, one frequently

228

K. ROEDER

in sizes to evaluate "matching" termsof a percent matchcriterion error. For example,the Lifecodes to is referred as a 1.8% matchwindowbe(3 SD) is cause theirstandarddeviation ay = 0.006y. Confor window mayoccurbecause an equivalent fusion the ForensicScience Service (a testinglaboratory larger in Great Britain)wouldrequirea somewhat techniques theirlaboratory matchwindowbecause lead to largererrors. A floatingbin methodis used to obtain"allele" by is probabilities.This probability estimated the population in offragments the reference proportion {zlj, z2j, j = 1,.. .,r} withinthree standarddeviasample: tionsofthe evidentiary Y -2 E ElI Ir
2

for methods calculating The NRC panel dismissed (1991) andothers, 12Z basedon(5),espousedbyBerry step (see Section6) on whichbypassthe matching the basis that theyare too complicated.They also in judgment thedeclaration the opposed use ofexpert methods. onlyobjective endorsing ofa match, for The NRC panel proposeda novelmethod calTheir suggestion, "probabilities." culatinggenotype ge15-20 "relatively from individuals 100 unrelated withexamples populations, homogeneous" netically Russians,Navajos,Puerto beingEnglish,Germans, amongothers.One would Ricansand WestAfricans, these populations from estimateallele probabilities Then used forensics. the for VNTRlocicommonly for one DNA profile, wouldchoosethe for particular any foundamongthe study allele probability maximum theyadd the (the ceiling). In addition, populations thatno allele probability shouldbe below condition 10% (the floor).Untilthese samples are obtained, an method. ceiling theyrecommended interim conby was The committee motivated thefollowing of the siderations. Strictly speaking, assumption independencedependson the absence of population in an heterogeneity, issue discussedfurther Section inferred that"in a popu3. The committee correctly allele eachwithdifferent groups lationthatcontains the [probabilities], presenceof one allele in a perof can expectation son'sgenotype alterthestatistical the Although comtheother allelesin thegenotype." no studieshave detected mittee notesthatempirical within acrossloci,they or violations independence of for population a chose"toprovide method estimating in a mannerthatwould adequatelyacfrequencies heterogeneity]." for count [population exWhen considerable populationheterogeneity has population a sigists,thechoiceofthereference Thereof on nificant impact theweight theevidence. of "the recommends approaches makfore, committee of thatare independent therace ingsoundestimates Theyclaim"theceilor ethnic groupofthe subject." eliminatesthe need forinvestigating ing principle because it yieldsan uptheperpetrator population, that boundtothe [probability] wouldbe obtained per bythatapproach." The NRC panel suggesteda second calculation, rule. That is, whichtheydubbedthe "one-on-N" database is reference population ifthe appropriate of size N, and if no one in the database matches the evidentiary sample, then 1/N should be presentedas an upperboundon Pr(9e). This calculato tionwouldbe presented thejuryalongwithorincalculation. As noted stead ofthe ceilingprinciple rule seems the by the panel, however, "one-on-N" to be at odds with analyses of existingdatabases: DNA proof "pairwisecomparisons all five-locus filesin the FBI database showedno exactmatches;
dubbed the ceiling principle, is to obtain samples of

j=1 z=1

Y-zij l < 3ay}. ly

is probability obtainedby multiThe multilocus plicationwithina locus and betweenloci withone maybe due to pattern exception.[A single-banded fragin to homozygosity, difficulties distinguishing mentsofsimilarlengthsor to an allele too smallto does not occur be measured. The secondproblem are techniques used. To aclaboratory whencertain whichmayhave the countfor twophysicalartifacts is the adjustment made: replace occurred, following emor -(y)2 with 2%2(y) 2-(y)2 if the methodology makesthe secondtechnical ployedin thelaboratory in unlikely.As mentioned Berry(1991), difficulty for morethan compensates the disthisadjustment is (2), mimicking ?/R calculated. Finally, turbance.] relieson a technique match/binning A competing apor fixedbin (Budowle et al., 1991ib) histogram is proachto calculate /R. The histogram formed the which define fixed boundaries based on arbitrary are adjustments made bins. Certain conservative withthis method:forexample,if any bin contains data from reference the observations thanfive fewer set, then adjacent bins are pooleduntilthis lower limitis achieved. largenumhave sampled laboratories The forensic each majorethnicgroup from bers ofDNA profiles (Caucasians,African populations to use as reference Hispanics,Asians,etc.;see Section5.2). Americans, 12Jis calculatedformost,or all, ofthesereference are and usually all ofthe calculations populations, to presented thejury. of 2.4 Recommendations the NRC Report (NRC, 1992) made manyrecomThe NRC report one DNA profiling, including mendations concerning of interpretation the evion the statistical chapter dence. This sectionwill exploresome ofthe statisthe that have affected ticallyrelevantsuggestions of JR. calculation

DNA FINGERPRINTING:A REVIEW OF THE CONTROVERSY

229

match the closest matchwas a single three-locus Thosestudcomparisons. pairwise among7.6 million thatmultiplication as ies are interpreted indicating across loci does not lead to of gene [probabilities] major inaccuraciesin the calculationof genotype
." [probabilities]

3.1 The Model

3. THE QUESTION OF INDEPENDENCE assume approximate typically Forensicscientists loci. and within between of independence allelesboth mostofthe initialcontrostirred This assumption (e.g. Caucasians) group or A versy. population ethnic (Irish,Italian, French, subpopulations composedof distributions allele probability etc.)havingdifferent heterogeneous.The mostlikelyviois considered hetpopulation resultfrom lationsofindependence of causes dependencies alheterogeneity Population loci and between (Li, 1969). Severalauleles within heterogeneity thatpopulation thorshave suggested of lead to a seriousunderestimate the probacould matching (Lander,1989, two DNA profiles bilityof 1991a, b; Cohen, 1990; Cohen, Lynchand Taylor, have counand 1991). Othergeneticists statisticians while the argumentthat heterogenetered that, hucorrect, ity causes dependenceis theoretically enoughheterogenerarelyexhibit man populations calculaimpacton forensic ityto have a substantial 1990; Chakraborty and Roeder, tions(Devlin,Risch and and Kidd, 1991; Chakraborty Jin, 1992). Exocbut these exceptions ceptionsexist,theyargue, such as a few isolatedpopulations cur in extremely tribes. Amerindian modelforpopulation In Section3.1, a probability an This modelpredicts is heterogeneity developed. claimthefirst In paper excessofhomozygotes. fact, based thisclaimon an of ingviolations independence In apparentexcessofhomozygotes. Section3.2,this the resultofa physical claimis shownto have been subsections, artifact (coalescence).In theremaining are various tests ofindependence described.Valid the find independence (approximately) pretestsfor of a largenumber when of dictednumber rejections Tests forindependence testshave been performed. artifacts (coalescence thatdo notmodelthephysical measurement error)have routinely and correlated Of of rejections thenullhypothesis. spurious yielded size increases,even minute course,as the sample lead to a will violationsofindependence eventually In hypothesis. Section of rejection theindependence the illustrates neg3.6, a MonteCarlo experiment when observed probabilities on profile ligibleeffect a pair oflociis ignored. between the dependence
erogeneity(also known as population substructure).

that allele distribution the effect To understand probahas on the calculationofgenotype variation case. The model bilities,considerthe single-locus assubstructure assumesindependent ofpopulation (random of sortment alleles withina subpopulation mating)and limitedmatingsbetween subpopulamodelis probsubstructure tions. This population abilistically equivalentto assuming that the vecfor torofallele probabilities a givensubpopulation on ulationand that,conditional G, an individual's For pair ofalleles is sampledindependently. examdisallele probability ple,in Figure4 the estimated at tributions D4S139 and D1OS28 are depictedfor of foursubpopulations Asians: Chinese, Koreans, the Japanese and Vietnamese. Ignoring nonneglithe in error theseallele distributions, giblesampling from genotype a of probability observing particular a Japanesepersoncan be calculatedbymultiplying theJapaneseallele probabilities (6) Pr ({a(i),a(j)})
=

G = (G(1), G(2),.. ., G(m)) possibly varies by subpop-

j { G(iG)2

ifi -j.

the Comparing resultofthis calculationto a simifor lar calculation a Koreanpersonyieldsessentially for probabilities locus D4S139, identicalgenotype for results D1OS28. (Muchof different butsomewhat data couldbe due to samplingerror; thisdifference Coroner's from office.) obtained OrangeCounty to of Supposetheperpetrator a crimeis known be is Asian,buthis subpopulation unknown.If an adis database foreach subpopulation equate reference can probability be calculated available,thegenotype as a weighted averageoverthe various subpopulations:
Pr ({a(i),a(j)})
(7)

2 E w(k)Gk()Gk(j),
lE

if i =/j,

w(k)Gk(i)21
k

if i = j,

of wherew(k)is the relativefrequency the kthsubThis calculation in yields population thepopulation. of {a(i), a(j)} thetrueprobability drawing genotype H-Wholdsin the provided the from Asianpopulation is defined subpopulations.If no information availin the able concerning allele probabilities the subscientistmightmake his the populations, forensic based on themixedAsian reference popcalculation in H-Wholds(approximately) the assuming ulation, probability is If mixedpopulation. ny(.) the marginal thentheprobabila(*) ofobserving in thepopulation,

230

K. ROEDER
BINNED FREQUENCY
CHINESE, JAPANESE, KOREAN & VIETNAMESE

A
0.25 0.20.150.1

DATA - D4S139

to assuming thereis no heterogeneity thepopulain tion: in otherwords, discarding secondtermin the bothcases. Clearly thisleads to an underestimate of theprobability wheni =j, and it willusuallylead to an overestimate wheni /j. A geneticmodel, based on evolutionary theory, leads toa one-parameter modelfor variancesand the in covariances (8),
E [G(i)]
=

(i), -Y(O)Y(i)

0.05 -zz
0

z
6 8 10 12 14 l| lW 16 18 20 22

z~
24 26 l 28 30

(9)

var [G(i)] =Os y(i)[1 - y(i)], cov [G(i), G(j)]

=

.,,,,,,,,,, 2 4

CHI

M JAP

1KOR

_ VIE

(see,e.g.,Weir, 1990). In genetic parlance, is analOs model ogousto FST ofWright (1951). A parametric forG withthe same moments theDirichlet is
G
=

(G(1), G(2), ... , G(m)) -(2),.. Dirichlet(Qy(1), , Y(m);Os)

B
0.16

BINNED FREQUENCY DATA D1OS28

CHINESE, JAPANESE, KOREAN,VIETNAMESE

3.2 AnExcess ofHomozygotes?

0.12

0.0 0.02
2 4 6 8 10 12 14 16 18 20 22 24 26 28 30

CHI

JAP

KOR

VIE

FIG. 4. Fixed bin distribution (histogram) twoloci and four for Asian subpopulations (used withpermission fromJohnHartmann):theboundaries the30 bins(vertical of axis)aredetermined binsare notofequal length. bytheFBI; these Samplesizes(numKorean and Vietnamese bers individuals) Chinese, of for Japanese,

axis bins forD10S28. Thehorizontal is thebinnumber; are notof equal length.

are 103, 125, 93 and 215 for D4S139 and 120, 137, 100 and 193

An obviousconsequence (8) is that population of in leads to an excess ofhomozygotes heterogeneity the mixedpopulation.This resultis well knownto over geneticists.Indeed,the controversy indepenwas denceassumptions ignited a claimthatan apby indicateda "spectacuparentexcessofhomozygotes lar deviation from H-W"(Lander,1989). Specifically, an excessof9 and 13%homozygotes claimedfor was D17S79 and D2S44, respectively. obtaininsight To intotheextreme heterogeneity impliedbythesefigof ures,examineFigure5. Considera mixture two one constructed drawing populations: population by the and pairs ofalleles from upperdistribution the otherconstructed drawingpairs of alleles from by of thehanging A distribution. population composed a of 50-50mixture thesetwoextremely disparatepopleads toonly 5% excessofhomozygotes! a In ulations fact, relevant no have shown amount the populations ofdifferentiation in illustrated Figure5.
3.2.1 A physical artifactmasquerading as population substructure

the ityofobserving genotype {a(i), a(j)} is calculated using(1). substructure the In general,assuming population the genotype of model, the probability observing is a {a(i),a(j)} in a randomdraw from population calculatedas correctly Pr ({a(i),a(j)}) (8)

f2-y(i)-y(j)2cov[G(i),G(j)], +
_y(i)2 var[G(i)], +

ifi =j.

ifi Ij,

is Assuming H-Win the:ntirepopulation equivalent

The data Landerbased his claimuponwerefrom LifecodesCorporation. Devlin, Risch and Roeder thesedata, in largepartbecause (1990) reexamined sucha hugeexcessofhomozygotes wouldbe unusual fortwo reasons: (i) extremeheterogeneity would rarelylead to such an excess; and (ii) relevanthuman populationsare not very heterogeneous (see Mourant, Kopec and Domainewska-Sobczak, 1976; Nei and Roychoudhury, 1982). In the absence of measurement it error, would be simpleto construct test to determine there a if are significantly homozygotes thepopulation more in

DNA FINGERPRINTING:A REVIEW OF THE CONTROVERSY

231

CDa
0
13

4'4

(16

image (hanging distribution). The horizontal axis is the number of repeating units.

a used allele FIG.n~~~~~~~~ distributions tocreate mixed 5. Twvo population: and thedistribution D17S79 (upperdistribution) its mirror for

than we would expect based on (8) and (9) (Levene, 1949). Let us consider a simple extension,which allows forcontinuous measurement error.Let
tE

,VvaiZ(O - ~EY

OE0 EE

Rischand Roeder,1990). The mostlikelyexplanathis tionfor phenomenon coalescence is (Section 2.2). Withsome effort, coalescencefunction be the can estimated from data using natural generalizathe tionsof(10) and (11); a smooth logistic curvefits the data. Fore largeenoughthattheprobability coaof lescenceis less than 0.01, t6 is no longersignificant for data setsexamined the (Devlin,Rischand Roeder, 1990). Therefore apparent the excessofhomozygotes can be explained closeheterozygotes by masquerading as homozygotes, ratherthan a seriousviolation ofmodelassumptions. It is important bear in mindthatthiscomposite to test is not a complete test ofH-W.Nevertheless, it has reasonable powerto detect population substructure. To demonstrate factempirically, this Devlin, Rischand Roeder (1991a) created mixedpopulations byrandomly sampling from Lifecodes African American and Caucasian databases. For such mixtures of 1000 profiles from each ethnicgroup, theyfound nearly 100% powerto detectmixture at least for one ofthe threeloci (D17S79, D2S44 and D14S13). On the other hand,Devlin and Risch(1992b) found suchmixtures induced in smallerrors only relatively estimates.These experiments genotype probability suggestthat the amountofpopulation heterogeneity withinthe forensic databases is substantially less thantheamount variability of between observed Caucasians and African-Americans. weakness One ofthistest,however, thatit can be affected coris by related measurement error (Greenand Lander1991; Devlin,Rischand Roeder, 1991a) and so mustbe interpreted carefully.
3.2.2 A Bayesian analysis of the data

of violations theindependence Slight assumptions in are to be expected anyhumanpopulation. Ideally (10) OE =-El It zlj - Z2j I < El we wouldliketo obtaina posterior of distribution Os j=1 thatwouldindicate variability G oversubpopthe of ulations.Based ontheposterior distribution, adjustof number e-homozygotes is the observed (fragrnents ments 2R indicated (8) couldbe madethatrely to by One can eswhich are separated by no more than m). on the covariance in structure indicated (9). Roeder under of number (-homozygotes timatete expected et al. (1993) have obtaineda resultofthis typeusH-94) usinga U-statistic ing a hierarchical Bayes approach.Theirmodelhas fivelevels; each level is supported theory andlor by 2r data: experimental (11)~~ -zj I < El, E- 2r - 1 1: I{lzj
j

where

<j

i wherefzi,

fromthe population of interest, ignoring the pair-

of 2r} is thecollection fragments

one to normal, ings. Ift, is largerelative a standard For thereis an excessofhomozygotes. can conclude = for e 0.0001, t. is highlysignificant several loci t6 and severalpopulations.For example, = 84.5 for t6 theCaucasians at D2S44; butif? iS increased, de(Devlin, ceases to be significant creases and quickly

1. (X1,X2) appear as (X1+ X2)/2withprobability determined the coalescence function. by as 2. (X1,X2), are given(A1,A2), distributed a biwithmean,varianceand covarivariatenormal ance determined (A1,A2). by 3. (A1,A2), givenG, are independent samplesfrom G. 4. G, given (y,Os), is distributed a Dirichlet as (y;Os).

232

K. ROEDER

5. A prior ay obtained experimental data, for is from for and a conservative'-prior Os,based on previis ous studies, beta(1,49). distribuIn their analysis theyobtainposterior near tionsofOswithmodes(and upperpercentiles) 0. For example,in D17S79, D2S44, D14S13 and for mode(95thpercentile) CauD18S28 theposterior 0.0015 (0.007). This indicasians is approximately in cates thatthereis almostno variability the allele It of distributions Caucasian subpopulations. would an of be simpletoincorporate estimate OsintocorrecFor assuming tionsto the X2R calculations. example, structure (9) is approximately in thatthecovariance Pr({a(i), a(j)}) can obcorrect that Osis known, and (9) tainedbysubstituting into(8) to obtain Pr (9e,79IHI) (12)

imizethe teststatistic.Not surprisingly, contradictory resultswereobtained. Presumably to circumventthese difficulties, Geisser and Johnson(1992) recentlyproposeda quantilex2test forH-W.The steps ofthe test are as follows: (i) Order the 2r fragmentsby size z(l) < howmanyquan(ii) Decide a priori Z(2) < * <Z(2r). tileswillbe used; call thisnumber (iii) Choosebin q. boundaries . . ,bq- thatdividethe ordered varib1,, ates intoq subsets, each with = 2r/qmembers. f (iv) Since zli < Z26 in twodimensions q boundaries the dividethe space intoq(q + 1)/2 bins. The number offragments in falling each bin is called Oij. Define if Ei = r/q2 i = j and Eij = 2r/q2if i / j. (v) Underreasonablechoiceofq, the Pearson'sx2 statistic x2 obtained from thisprocedure distributed with is q(q - 1) degreesoffreedom underthe H-WhypotheGeisserand Johnson (1992) claimthattheonlyasof sumption theirtest is bivariateexchangeability. This claimis challenged Devlinand Risch(1993), by whoshowvia simulation thatphysicalartifacts confound testofH-W. the Theirarguments based on are thecomplications introduced coalescence and corby related measurement error thatarenotallowed in for Geisserand Johnson's test. Coalesencecauses an excess ofmass in thebinsonthediagonaland a dearth ofmass in the adjacentoff-diagonal bins. The effect is ofcorrelated errors morecomplicated, it although is clearthatthepotential confounding present for is from (4). The goal is to assess violationsof indethe pendencein (A1,A2);however, test is based on whichare clearly (X1,X2) correlated through(61,62). The testis moresensitive thiseffect to whenthe allele distribution very is witha few comuneven, very in monalleles creating "ridges" thetwo-dimensional surface (Figure2). Weir(1992a) also examinesthe questionofindebins pendence usingbinneddata. He uses the fixed set by the FBI, discarding the bins on the diagonal to removethe effect coalescence. (Weircorof out is rectly points thatthere noneedtobe concerned about the H-W assumption homozygotes, for using the FBI's method, because H-W is not assumedfor homozygotes onlyone allele is used in the calcua lation.) He forms test statisticusing the likelihoodratiotest. Because thedata are sparse,he uses a bootstrap the to resampling procedure determine null distribution the teststatistic.Unfortunately of and cothistestis also sensitive correlated to errors alescencebecause ofthe dearthofmass in the offeven withthis disturbance diagonalcells. Notably, in thedata,Weir showsmost and mostdatabases loci In conform H-W expectations. a similaranalysis to ofthe Lifecodes database,he obtainsresultsgenerally supporting H-Wand linkageequilibrium (Weir, 1992b).
SiS.

Y(i)2+ Osy(j)[1 - y(i)],

2y(i)'y(j)(1 - Os),

ifi =j, ifi =Ij.

A fullBayesian correction involves integrating (12) of to overthe posterior distribution O, Corrections are population heterogeneity devel(2) thatallowfor in opedfurther Section4.

3.3 ClassicalTestsofIndependence
is mixture subpopulations nottheonly of Ofcourse, and of possibleviolation theH-Wassumption, efforts of for violations theinhavebeenmadetocheck1 other test assumption.Perhapsthe simplest dependence relevantto VNTR data is Fisher'sintraclasscorrefor lation. This test is equivalentto testing correin lationin the set ofpairs offragments the reference population{(z1j,Z2j),(Z2j,Z1j),J = 1, ... ,r*} and r* j = r*,. .. , r}, wherethe first measure{(Zlj,Z2j), Such analysesrementsdenotethe heterozygotes. if between veal little, any, paternaland relationship (Budowleet al., 1991a; Berry, maternalfragments Evettand Pinchin,1992; Weir, 1992a; Chakraborty, Srinivasanand de Andrade, 1993). An advantageof is to theintraclasscorrelation its insensitivity some discussedin Secofthe electrophoretic phenomena below. tion2.2, unlikeothermethods Testing the assumptionof H-W for a populafor tion is oftenstraightforward classical genetic markerdata. These tests measure the difference number each of and expected betweenthe observed the population in distinct genotype a sample from to 1989). Initialefforts testH(Hernandezand Weir, to standardx2methods binneddata W by applying ad At were plagued by difficulties. first, hoc techthe of niqueswereappliedinwhich number binsand to or theposition binswereselected maximize mmnof

DNA FINGERPRINTING:A REVIEW OF THE CONTROVERSY 3.4 Tests of Linkage Equilibrium

233

as Mixtureof subpopulations, well as evolutionmayinduceassociations suchas selection, aryforces loci. betweenalleles at different Weir(1992a,b), usabove,has thoring testssimilarto thosedescribed oughlyanalyzedthe VNTR databases forviolation Againhis analysesrevealno oflinkageequilibrium. independence. from largedeviations
3.5 Composite Tests of Independence between Loci

causes an association Population substructure According those to amongalleles in VNTR profiles. evaluationofthe scientists' criticalof the forensic If can this DNA evidence, association be substantial. would someVNTR profiles is the association strong, in database moreoften themixed occursubstantially underindependence.For than would be predicted for data, a classicaltestofindependence two discrete of tablewith the locirequires construction a two-way for loof rowsconsisting possiblegenotypes thefirst of for consisting possiblegenotypes cus and columns approach the secondlocus. Using a nonparametric large,sparse table to a that reducesthis extremely 2 x 2 table, Risch and Devlin (1992a, b) examined databases to deterboththe FBI and the Lifecodes in occurs thedatabases. mineifan excessofmatching for loci, matchprobabilities individual To estimate of theymade all r(r- 1)/2possiblecomparisons the r individualsin each database. A matchwas dediffered measurements clared if the corresponding Thisis an standarddeviations. byno morethanfour that a random, innocent estimateofthe probability samplewouldbe declared suspectand an evidentiary a matchbychance. the occurassumption, Under the independence at renceofgenotypes pairsoflocishouldbe indepenthat the dent.Therefore, probability twoindividuals at have matching genotypes a pair ofloci shouldbe matchprobabilities. the productofthe single-locus violations pairwiseindependence, of they To testfor the 2 constructed x 2 tablesfrom r(r- 1)/2comparlocus being isons,withmatch-nomatchat the first matchat the secondlothe tworowsand match-no values forthe cus beingthe columns.The expected the of from product thesingle-locus cellsare obtained the matchprobabilities. they Although teststatistic of used has the form Pearson'sx2, it does not folBeunderthenullhypothesis. low a x2 distribution the cause the entriesin the table are U-statistics, variancethan a classicaltestofintesthas greater to dependence. Using the methodofbootstrapping of obtainthenull distribution theteststatistic, they of violations indid notfindevidenceforsignificant dependence. See Herrin(1993) forsimilarresults usingdifferent databases.

Under the populationsubstructure hypothesis, morematches expected are thanare predicted inby dependence, providedthe different subpopulations actuallyhave different allele probability distributions.The analysessuggestthat,whatever disequilibrium existsamongloci,it has littleeffect the on probability tworandom of individuals havingmatchinggenotypes. Rischand Devlinexplaintheir results as indicating thatsubpopulations notdiffer do much in theirallele distributions, least forthe ethnic at groupstheystudied. In fact,theyargue (see also Devlin,Risch and Roeder,1993a, b) that the genotypeprobabilities differ morebetween ethnic groups than withinethnicgroups-contrary the arguto mentsofLewontin and Hartl (Lewontinand Hartl, resultssupport 1991;Lewontin, 1993). Indeedother this supposition (see Section5.1). For instance,in mixed databasesformed randomly by selecting equal numbers African of American and Caucasian singlelocus profiles (500 and 1000 each), a greaternumber of two-and three-locus matches are observed usuthanare predicted theindependence by model, ally significantly greater (Devlin,Rischand Roeder, 1994). To evaluatethe powerofthistestto detectpopulationsubstructure, Devlin,Rischand Roeder(1994) again createartificial populations mixingequal by proportions Lifecodes of African and CauAmerican casian profiles (see Section3.2). For each subpopulation, they randomly sampledand combined singlein locusprofiles, thereby ensuring equilibrium each Wheneach subpopulation consisted subpopulation. of500 individuals, powerto detectmixture the was 69, 61 and 58% forthe locus pairs D2S44-D17S79, D2S44-D14S13 and D14S13-D17S79, and 33% for thethreeloci. For 1000 individuals each subpopin 95% for each pairoflociand ulation, powerexceeded the was 81% for triplet. It is important recalltwofactsregarding to these results: (i) such mixture does not cause large (relative) errorsin genotype probabilities (Devlin and Risch,1992b);and (ii) Rischand Devlin (1992a) detectedno violationsof independence the actual in Lifecodes data for theseloci,consisting over3000 of Caucasians and 2000 African Americans.(Unfortunatelythistest,liketheothercomposite test,can be affected correlated measurement by error.)
3.6 Sensitivityof AYktoAssumptions

The implicit assumption requiredformultiplying across loci is eitherhomogegenotype probabilities or neous populations randommating.Criticsargue that of are correctly thepopulations interest neither nor homogeneous randomly and thenargue mating, thatit mustbe wrong multiply to probabilities. As Evett,Scranageand Pinchin(1993) pointout,clas-

234

K. ROEDER

do sical tests of significance not address the issue ofinterestdirectly:tests may fail to rejectthe inbecause theylack poweror, hypothesis dependence the hand,theymayreject independence ontheother consethereare no practical eventhough hypothesis of quencesofthefailure the assumption. Evett, Scranage and Pinchin(1993) Therefore, to a performed Monte Carlo experiment examine violations. of significance independence thepractical ScienceLaboratory PoliceForensic The Metropolitan eachwitha of of databaseconsists a file r individuals, (D1S7, D7S21, D12S11). For any profile three-locus for )YR, calculated underHO, all possible twoloci,they [i.e.,r(r- 1)/2 1.2 x 106] for pairwisecomparisons as(dependence twosettings:(i) the database itself by sumed)and (ii) a database constructed randomly of the reassigning profiles one locus (independence of is certain).The expectation thatthevast majority zero undereither(i) or the Z9Z'swill be essentially largerfor(i) under willbe stochastically (ii), but 12R modelbecause,ifthere substructure the population alleles in a subpopulation, between is an association in a comparison persons thesame subpopubetween values ofLkR. lationshouldlead to inflated they In the three between-locus comparisons, distribetween found difference onlyone significant thispair ofloci butions(D1S7, D7S21), but evenfor to did thesedistributions notdiffer a degreedeemed significant.For example,the observed practically an of frequency reporting IYRin excess of 1000 is withan exabout 3.7 cases per 100,000,compared pectedrate of2.7 cases per 100,000. of See also Brookfield (1992) fora discussion the at subdivision a singlelocus. effect population of 4. REFERENCE POPULATIONS issues thatoneofthethorniest doubt Thereis little debateis thatofselecting in theDNA fingerprinting reference an appropriate population.A basic questionis treatedin Section4.1: Shouldthe reference of consistofindividuals the same ethnic population that an innocent groupas the suspect? Assuming suspectis unrelatedto the donorofthe evidentiary is sample,the answeris no,his ethnicity irrelevant In unlesshis guiltis presupposed. somecases it can shouldbe weakened, be arguedthatthisassumption between for allowing variousdegreesofrelatedness thatthe from and the suspect, the culprit assuming of culpritand suspectare members the same suband suspect to population assumingthatthe culprit It are brothers. is possibleto adjust CZ to allowfor For theseweakerassumptions. reasonsofgrammatithe to cal ease, I refer theindividual donating evidenthis throughout section, tiarysampleas the culprit, In although thisis legallyincorrect. Section4.2 the the suspectis assumedto be from same subpopula-

tionas the culprit, in Section4.3 the suspectis and assumedto be a closerelativeofthe culprit. The conclusions thissection be summarized of can as follows.The ethnicity the suspectis not releof vant,unlessthe suspectand culprit assumedto are be from same subpopulation.Because usually the littleis knownabout the culprit, is generally it assumedthatthe suspectand culprit possibly, are but not necessarily, from the same subpopulation (unrelated). Some people argue that they should be assumed to be from same subpopulation all the in cases (Nicholsand Balding,1991). This distinction is notas important onemight as initially expect.The correction thesuspectand culprit for beingfrom the same subpopulation littleeffect theweight has on of the evidence, unless the heterogeneity consideris ablylargerthan that observed mostforensically in important populations.Whenthe suspectand culpritare close relatives,the correction may have a largeimpact.Brothers considerably are morelikely inDNA profiles tohavematching thanareunrelated dividuals. Ignoring relatedness first of cousinsalso leads to an inflation the weightofthe evidence; of it however, is notdramatic.
4.1 Whose EthnicityMatters?

In Vermont, the defensesucceeded in blocking the admissionof DNA evidenceby demonstrating that the suspectwas ofmixedAmerindian, Italian and Frenchancestry thenarguing and thatthe FBI lacked an appropriate reference for population this case becauseitdidnothave a database ofindividuals mix(Weirand Evett,1992). Was this ofthisethnic based on fallacious ruling thinking? In orderto clarify the key issues, assume that erin without the genotypes (2) can be ascertained ror. A question arises: is Pr(9) to be calculated of based on a reference population composed individmixas the suspect(suspectuals ofthe same ethnic based sampling) individuals or whocouldhave committed the crimeby virtueofhavingaccess to the and so crimescene, fitting eyewitness description states on (culprit-based The NRC report sampling)? out have that"Somelegalcommentators pointed that of be should based onthepopulation posfrequencies to ratherthan on the population sibleperpetrators, this whicha particular suspectbelongs. Although often is argument formally correct, practicalities preof cludeuse ofthatapproach." Regardless any"pracit thatthelegal system ticalities," is critical giveseto reference riousconsideration theappropriate popthe case. To clarify issues, ulationin anyparticular let us lookat theformal logicputforth Evettand by Weir(1992),whichsupports culprit-based sampling. The argument based on twokeyassumptions is that have beenthesubjectofdebate.

DNA FINGERPRINTING:A REVIEW OF THE CONTROVERSY

235

relevant information aboutthe Let Seand J, denote such culprit and suspect,respectively, as the ethnic is The objective to calculatethe likelibackground. hoodratio
(13) z I H1 Pr (9e X9s XSe, Xs) Pr (9e7 9s IHo Je,as)

about ASSUMPTION 1. The relevantinformation about withthe information is the culprit consistent the suspect:ae C :Js. is of The consequence thisassumption thattheinsuch mustnotbe contradictory, as thesusformation is pect is whiteand the culprit knownto be black, of because thenthe probability H1 is 0. Takingthe write )2/as of sampling, viewpoint suspect-based (9s IH1iieifJs) (14) Pr (9e I 9s,Ho, Je7 Js) Pr (9s IH0i Jei Js)
jJe4Js) Pr Pr(9e 19s, Hi,

from same subthe the same family necessarily nor a population. Occasionally goodcase can be madefor between suspectandthe the somesortofrelatedness culprit underHo. For example,supposea crimeocin are curred Seneca,Kansas, wheremostresidents ofGerman and and thesusdescent, boththevictim of pectare Senecans. Ifthecircumstances thecrime is indicate thattheculprit a local,chancesare fairly is highthattheculprit ofGermandescent. substrucof The statistical properties population described Wright by (1951), and furturewerefirst (1969, 1972); these therelaboratedby Cockerham used to have beenrecently theoretical developments extendthe calculationof )2R to allow forsome relatedness(Nicholsand Balding 1991; Balding and 1992;Weir, 1994). Nichols, 1994;Morton, and ASSUMPTION Affinal 3. model.The culprit susthe pectderivefrom same subpopulation. reference the Undertheaffinal model, appropriate howis of population the subpopulation the suspect; the laboratory possessesan inever, typically, crime amountofdata forthis approach.Neversufficient can theless,calculations be based on the largerreferencepopulation.We illustrate these ideas using a one locus marker.Assume 9e = 9s = {a(i), a(j)} = the and calculate1/2CR Pr(9eI9,7Ho) byextending used to obtain(9), reasoning
Pr (9e I 9s7Ho) 2 [Os + (1
- 8)Oy(i)] [Os + (1 - 0s)Y(j)]

as can 2CR be equivalently represented

(15)

Pr (9O Pr (9O

9e,H1i iei Js) Pr(9e 9e,HO, Je

I Hi iJeiJs)

Js)Pr(9e IHII0JeiJs)

from convenient which representation maybe a more of theviewpoint culprit-based sampling. of then9e is independent 9s and as;furthermore, 9s of is independent 9e and ae. 2, By Assumption if 9e = 9s, then (14) and (15) to simplify (16) and
(17)
ASSUMPTION

model.IfHo holds, 2. Independence

+ ~~~(1 Os)(1 + 20s)

(18)
I

ifi /&j,
[30s [20s+ (1 - Os)-y(i)] + (1 - Os)y(i)] ~~(1 +Os)(1 +20s) ifi=j.

Pr (9s I Hi, Se Js) X Pr Pr (9s I Js) (9e I Je)

Pr Pr (9e I Je)) (9s Ias)

Pr (9e I Hi,Jei Js)

respectively.Because (14) and (15) are identical, Pr(9s I Hi, Je4 Js) = Pr(9e I H1, Jej Js). FromAssumpinto comes in tion1 thelackofsymmetry theproblem to of play-the numerators bothequationssimplify = that )2R 1/Pr(9eI Je) the We Pr(9s I Js). conclude cancelsout aboutthesuspect's information ethnicity was oftheequation.The court's reasoning fallacious, undertheseassumptions.
4.2 Subpopulations

are 2, By Assumption the suspectand culprit assumed to be unrelated,that is, theyare not from

based onthemoments Theseformulas be derived can whichhappento agree withevoluofthe Dirichlet, tionary theory (Baldingand Nichols,1994); similar evolutionfrom formulas have been derived directly arytheory Weir(1994). by If Osis bigger than 0, thenthis calculation yields model. less evidenceforH1 than the independence However,as noted in Section 3, for Caucasians see for Os 0.0015. Thissmallestimate Osis typical; a from valuesofOsobtained Morton (1992)for tableof humanpopulainformation concerning demographic tionsthatdo notincludeU.S. populations.U.S. ethnic groups,being a melting pot of subpopulations, are expected have smallervalues ofOs. See also to and Chakraborty Jin (1992). The resultsofthese as studies,and others, can be summarized follows: some majorethnicgroupsin the UnitedStates ex-

236

K ROEDER
TABLE 1

Alleledistribution Polesand Italians,obtained for from Lewontin Hartl(1991;LH) and Chakraborty Kidd (1991; CK) MGP = and and Pr(5),assuming independence (H-W)and population substructure (True) LH Locus Rh Kell ABO MGP MGP Allele cDe Cde K k A B H-W True Poles 0.047 0.044 0.058 0.942 0.370 0.220 3.69 x 10-6 1.19 x 10-6 Italians 0.006 0.015 0.015 0.985 0.370 0.070 Poles 0.042 0.030 0.043 0.957 0.259 0.145 5.24 x 10-6 5.69 x 10-6 CK Italians 0.033 0.011 0.049 0.951 0.239 0.142

Americans, (African hibit almost no heterogeneity amount heteroof a Caucasians), someexhibit minor hetenough (Hispanics),whilesomeexhibit geneity of on to erogeneity have an impact thecalculation Z22 (Amerindians). For the latter,separate databases isothatare largely keptfor tribes the are generally lated,such as theNavajos. a highlight logical in The calculations thissection of made bycritics the DNA methodflawcommonly ology(e.g., Lewontinand Hartl, 1991; Hartl and the positionthat Lewontin,1993). Arguingfrom reference popis a subpopulation the "appropriate" ulation,theytake the ratio ofthe allele probabilito population those reference ties in the appropriate calculations. This rainduced by typicalforensic tio is not relevantbecause it is a generaldatabase, that is used by composedof manysubpopulations, the scientists. Therefore errorin calculaforensic tion is the ratio of a calculationlike (6) to (1), not of allele probabilities subpopthe ratioofparticular by ulations. Take the examplepresented Lewontin and by and Hartl (1991) and rebutted Chakraborty for Kidd (1991). Allele probabilities Poles and Italfor ians are presented severalbloodgrouploci (see and HartlexpressconLewontin Table 1). Although probability cernthattheratioofthePolishgenotype is probability 247, the apto the Italian genotype of probability is comparison the genotype propriate obprobability Poles (7.4 x 10-5) to the genotype tained assumingH-W in the mixed Polish-Italian In difference. (3.7 x 10-5), onlya 2.0-fold population this a numberofthismagnitude, is hardlyan error ofpracticalimportance.In factthe data presented in Lewontinand Hartl are flawed. [Thesedata are and includetytaken froman outdatedreference and Kidd, 1991; pographicalerrors(Chakraborty Morton,Collins and Balazs, 1993). Repeatingthe with data,thereexperiment thefullsetofpublished
in another subpopulation as a measure of the error

The sultschangedramatically. multilocus genotype probabilities 5.74 x 10-6, 4.73 x 10-6, 5.24 x lo-6 are and 5.69 x 10-6 forthe Polish, Italian, H-W and (Chakraborty truemixedprobabilities, respectively Collins and Balazs and Kidd, 1991). See Morton, thereis (1993) forfurther discussion. Apparently usinga general littleharmin assumingH-Wand/or mixed thana subpopulation this in population rather instance.] In general, theappropriate reference population if and onlyan estimate is a particular subpopulation of Os is available,thenthe magnitudeofthe error a of can be obtainedfrom comparison Pr(9e19s,Ho) calculated using(1) versus(18).

4.3 Relatives

A more "the is seriousconcern based onthedefense was mybrother" culprit (Evett,1992b). Usingstan?/R dard genetic principles, can be calculatedwhen is of theculprit assumedtobe a relative thesuspect. locus, identicaltwins For example,at a particular from shareboth allelesidentical descent by (inherited have a the same parent);fullsibs (regular brothers) bothalleles,oneal25, 50 and 25% chanceofsharing by respectively. lele and no alleles identical descent, which can Ofcourse they also shareallelesbychance, is called identicalbystate. Fromthis we can infer how the thatnomatter polymorphic genetic markers, thereis at least a (0.25)L chancethat an individual at matcheshis brother L loci [theexactprobability
+ forfullsibs is [1 + 2Ek'y(k)2

(Weir, 1993)].

2(Eky(k)2)2

Yky(k)]

/4

is ASSUMPTION 4. Cognatemodel.The culprit a relativeof the suspectwith probability of havcp 1940) ingp alleles identical descent(Cotterman, by of and genotypes the parents of the suspect are

DNA FINGERPRINTING:A REVIEW OF THE CONTROVERSY

237

in a region wherethevast majority thepeoplebeof longto a subpopulation (e.g.,German ancestry) an of If 9e = 9s = {a(i), a(j)}, then ethnic group(e.g.,Caucasian), the forensic scientist evaluates the evidencebased on the ethnicgroup, Pr(9e I 9s7HO) notthe subpopulation. justify To this approachtwo C2 + c 1y(i) + Coy7(i)2, arguments made: (i) individualsof othersubare if i =j, J (19) had access to the crimescene;(ii) there populations C2 + C1 [y(i)+ y(j)] /2+ 2coy(i)y(j), is littledifference between subgroup the and ethnic i zlj. t ~~~~~~~~~~if group profile probabilities, thisdifference miand is nor relativeto theirconservative evaluationofthe is from calculation consider- evidence. this Clearly 2R obtained in ablylargerthanthatobtained (2) whentheculprit It is true that binningmethodsgenerallyyield (for relatedas a brother full is allowedtobe as closely smaller2R's than the statistical methods(see Secsibs c2 = 1/4, c1 = 1/2, co = 1/4). For individuals as tion6). Nevertheless, from statistical the perspecis cousins,the effect already closelyrelatedas first tive, the forensic scientist'sargument invitestwo relativelyunimportantas c2 = 0 and c1 = 1/4. questions: Are the differences among subgroups two wantto entertain nullhySupposethe courts small relativeto the variationamong individuals potheses: within subgroups a (known be vast) and thevarito ationamonggroups(known be relatively to small)? from unrelated Hoo: the sampleswereobtained Are the reference databases a reasonablyaccurate individuals; reflection the ethnicgroup?These questionswill of be addressed Sections5.1 and 5.2, respectively. in from brothers. Ho,: the sampleswereobtained One basic conclusion be drawnfrom can this section. Despite concernabout heterogeneity among odds ofH1 no longer In this situationthe posterior the subpopulations, data show DNA profile probof factor in (3),hencetheprobability thecompeting as in intothecalculation a meaningful abilities are quite similar across subpopulations: enter hypotheses the dominating source of geneticdiversity can be way, attributed differences to amongindividualswithin a subpopulation. The relevantliteraturedemonodds (H1) stratesdiversity is amongsubpopulations less than Pr(H1) Pr (OS) IH1) 9e diversity among ethnic groups. Because of the + Pr(Hoo) Pr (9s 9eIHOO) Pr (Ho,) Pr (9S7 9elHol)' tremendous amount genetic of variability amonginhas little dividuals, variability amongethnic groups Twolegal avenueshavebeenused bytheprosecution practicalimpacton the calculationof DNA profile whererelativesofthe suspectare also in situations for probabilities mostcases. Moreover, variabilthis that all near is undersuspicion. The first to verify and reported. itycan be observed Variability among theirDNA relativeseitherhave a solid alibi and/or has thanvariability subpopulations evenless effect does notmatch.Ifthisavenueis notviable,thenthe amongethnicgroups. Resultsofa studythat purwith2R's calculatedunderthetwo juryis presented portsto have shownotherwise explainedby a are separately. competing hypotheses bias in thestatistical did the methodology; study not for -, account sampling error. Concern aboutthequality reference of populations 5. GENETICDIVERSITYAND SAMPLINGISSUES obtainedby convenience samplingcan be eased by DNA profiles, the the same reasoning.Obviously, reasonableeffort a matching For a trial involving attormustbe takento obtaina representative the and forensic scientist, prosecuting defense sampleof the it withconveying unrelatedindividuals;however, appears that a neysand thejudge are charged of experiment notyieldresultsthat may significance the matchto thejurors. The signif- well-designed that differ population(s) measurablyfroma reasonable convenience icance dependson the reference a sample.Thispointis illustrated examining histo by are appropriate the case. The initialdecisionon from a obtained is theproper reference database; allele probabilities population madebytheforen- torical similarto randomsampleare remarkably others can stratified sic scientist theprosecuting and attorney; from convenience a resultsobtained sample. be advancedbythedefense less frequently, the by or, scientists of judge. For the majority cases, forensic refis believethegeneral population theappropriate 5.1 PartitioningDiversity the probability erencepopulation, evaluating profile Fromtheexisting for reference populations thathave in each ofseveralethnicdatabases gathered this is evenifthe crime committed been classifiedby major ethnic group (e.g., Caupurpose.Frequently,
-

unknown.

238

K ROEDER

it American), is apparcasian,Hispanicand African inbetween variability entthatthereis tremendous varidividualswithinan ethnicgroupand limited ationbetweenethnicgroups.In factthevariability thattheprobability is group so great within ethnic an is individuals matching vanishingly oftwounrelated small (Rischand Devlin,1992a). One wouldlike to popufrom thatthechoiceofreference this conclude of The importance. relevance thisrelationis oflittle if is however, there substantially sultis questionable, within betweensubpopulations greatervariability than the diversity) an ethnicgroup(subpopulation diversity). betweenethnicgroups(ethnic variability of Underthisscenariothereexistclusters individutwo Hence,although als withsimilarDNA profiles. from mixedpoputhe individuals pickedat random to lationmaybe unlikely match,twopeoplepicked morelikely to the from clustermaybe considerably match. base theirrecomThe authorsofthe NRC report on by espoused Lewontin mendations thisconjecture, by and Hartl(1991) and based onresearch Lewontin on has (1972). Muchattention focused thehistorical which have suchas bloodantigens of records markers groupand subpopulabeen classified bothethnic by to are tion.Theseresults relevant thedebatebecause and demographic charthe theresultsreflect mating ofhuman populations. The analyses of acteristics databases, as well as somemodern these historical VNTR databases,are discussedbelow. some notation: let Let us start by establishing withinethnicgroups,j = j index subpopulations i 1,... ,J; let i indexethnic groups, = 1,..., I; and let withinsubpopulation and j c index sampledalleles of ethnicgroupi, c = 1,... ,2C. For simplicity noC of tation,assume an equal number individuals is and sampledper subpopulation, likewise randomly J an equal numberof subpopulations is randomly group. sampledper ethnic be Forthecthallele,let Wijc(k) 1 ifthealleleis a(k) is Randommating assumedwithin and 0 otherwise. so a subpopulation thereis no need to distinguish or individuals. betweenalleles within between = Within (i,j)th level,the probability the Wijc(k) 1 variesover As is -yiu(k). in Section3.1,I assume yiu(k) and expectation the subpopulations has conditional (k) W - -.k(k . 'yi. and variance yiy.(k)(1Yi ))Os Suchvariabilof in ityinducescorrelation thegenesofindividuals a common group:
E [Wijc(k) yi.(k)]= Vi(k), I
E [WijckWlYijc' I Vi ( (k) W]

induces correlation betweenalleles sampled from the same ethnicgroupwithparameterSE denoting coancestry alleles in common of ethnicgroups, but different subpopulations,

E [Wij,(k) .. (k)] =(k), I

E [Wijc (k) () (k)Wijlc, WIy. = an (k)2+ ..(k)(1 - y..(k))OE. Lewontin (1972) proposeda partition diversity of based on a hierarchical application the Shannon of Information criterion. measureindividual To diverLewontin sity, suggested
=

01

1= -IJ E i
i

tYij(k) log-lij(k).

To measuresubpopulation diversity, suggested he

-I~ Evi-.
i k

(k)log'yi.(k) 01=

02 - 01

Finally,to measure populationdiversity, sughe gested

-

En..(k)logn..(k)
k

- 02 = 03 - 02-

comBecause each levelofthispartition a convex is diversities bination thelevelbefore, estimated of the mustbe nonnegative. of to of Ofcourse, obtainestimates thecomponents the diversity, 02 and q3 are obtained replacing by X1, allele probabilities theircorresponding unknown by of estimates.To studythe effect using estimatesof rather thanthetruevalues,we use allelefrequencies a Taylor to seriesexpansion 5(k)about-1(k), obtain of theexpected value ofy(k):
E [y(k)log '(k)]

(20)11

var log (y(k) y(k) + - -y(k) ['y(k)]. 2

+ = yi.(k)2 yi.(k)(1- yi.(k))Os.

to the Following same patternwe allow -yi.(k) vary 'y..(k). This over ethnic groups with expectation

It follows from the approximation (20) that 01,02 of and q3 are biased estimates.Because thenumber estimates (k), vi.(k) alleles sampledto obtainthe the increasesrapidly, variancesdecrease and y..(k) effect thatthesubpopulation is The rapidly. ultimate estimate tendsto possess a strong diversity positive Rischand Roeder,1993b,1994). This bias (Devlin, for bias dependson Osand SE and is reduced largeC. this to Applying method small samplesofsubpoparoundtheworld, ulationsfrom including groupsas remoteas Pygmies, Lewontinobtainedthe following breakdown: ethnicdiversity subpopulation and

DNA FINGERPRINTING:A REVIEW OF THE CONTROVERSY

239

of for accounted 6.3 and 8.3%,respectively, diversity 85.4%was atwhiletheremaining thetotaldiversity, same ofthe individuals among to tributable variation subpopulations. resultwas In the 21 years since this surprising varifor published,standardmethods partitioning 1969, 1972) (Cockerham, ance have been developed exists(Smouse, results of and a largebody consistent Spielman and Park, 1982; Nei and Roychoudhury, Collins and 1982; Chakraborty Jin, 1992; Morton, and Balazs, 1993). These resultsindicatethatsubby is populationdiversity dominated ethnicdiversity. Even a study(Latter,1980) using Lewontin's and populations loci,but as methods, well as similar that5.6% of largersamplesfound withsubstantially between to was thediversity attributable differences amongethand subpopulations 10.4%to differences nic groups. nor Latter'sresultsare comNeitherLewontin's likethe societies applicableto industrialized pletely to UnitedStates because theygive as muchweight small isolated populations(e.g., tribesofPygmies) thathave popas to the large open subpopulations ulated the United States. In this regard,Nei and resultsare moreapplicable. They Roychoudhury's also foundthat ethnicgroupsaccountedforabout but 10% ofthe diversity, only0.5% or less was atand Germans to amongEnglish, tributed differences societieslike the United Italians. In industrialized based on variance States, the estimateofdiversity is amongsubpopulations ofVNTR allele frequencies 0.1% (Morton, usually quite small-approximately Collins and Balazs, 1993; see also Budowleet al., 1994). resultspresented The calculationsand empirical thatLewontin's contradictory in thissection suggest results can be explained,in part, by samplingerfails diversity to acfor ror.His method partitioning countforsamplingerrorand henceleads to biased 1969, methods (e.g.,Cockerham, results.Competing 1984) are based on stan1972;Weirand Cockerham, for of dardpartitioning varianceand do account samplingerror.
5.2 Construction of Reference Databases

the perspective, construction Fromthe statistical database (say,U.S. Caucasians) is a of a reference colif simply straightforwardonerousproposition: Caucasians random samplefrom.U.S. lecta stratified of and obtainthe genotypes that sample. Human scientists less are and geneticists forensic population a To fastidious. construct Caucasian database,they collectand typesamples that are convegenerally bloodbanksandlaw enforcefrom for nient; example, and for mentofficers theFBI database,and mothers cases forthe Lifepaternity from putativefathers

scientists (and human codesdatabase. The forensic based in partonresults geneticists general)argue, in section, thatthereis little presented theprevious in random sampleand a difference between stratified a convenience samplefor theirpurposes.Statisticians are without knowledge humangenetics naturally of skeptical thisclaim. of to Thereare reasons, however, believethisclaimis for the of correct; instance, consider implications the diversity the previous in observations aboutgenetic subsection. Thereare also data thatbear directly on thisissue,inparticular, results a stratified of ranthe geneticmarkers(DHEW domsampleoftraditional below. 1980),whichare described A studythat obtaineda stratified randomsample oftraditional geneticmarkers(ABO; RH-C, D, and was E; Secretor status;haptoglobin; transferrin) of sponsored the Department Health,Education by and Welfare the during years1967-1970. The study to Amerstratified according ethnicgroup(African ican, Caucasian), sex, geographicregion (Northeast, Midwest,South and West),incomeand edufor cation. Justification the studywas that,while there existed numerousstudies of these markers in Kopecand from U.S. samples(compiled Mourant, 1976), "nonehad been ranDomainewska-Sobczak, and dom or systematic, none had been systematic Inrepresentative samples ofthe U.S. population." is but perhaps deed,thestatement true, theauthors the overstate need fortheirstudy(especiallygiven theirresults)whentheyarguethatpublishedallele couldnot"beconsidered representative a frequencies region." sampleoftheU.S. or anyU.S. geographic What is striking about the results of this study is how littlevariability thereis amonggeographic regions.See Table 2 forthe regionaldata forCauin casians. None ofthe regionaldifferences allele smaller have a probability occurrence of frequencies than 0.05 foreitherethnicgroup. There are also similarities between resultsofthestratthe striking ifiedrandomsample and the studies publishedin (1976). Mourant, Kopec and Domainewska-Sobczak Gilbert As an example, one such study(Niederman, a from samand Spiro,1962) examines twomarkers all ple of1000Yale students, Caucasian males. The resultsofthis studyare givenin Table 3. Apparthatthereis not muchgeentlyone mustconclude or in neticheterogeneity U.S. Caucasian populations a thatYale was doingan excellent ofobtaining job the representative sampleofU.S. Caucasians during years1958-1959,orboth. there the Regarding VNTR databases themselves, similarities betweenallele distriare again striking different butionsfrom regionsofthe UnitedStates forall major ethnicgroups(Budowle et al., 1994), despitethe factthat samplingerrormustbe large forthese relatively small databases. Chakraborty

240

K ROEDER
TABLE2

Genotype distributions Caucasianpopulation, locality for by [NE=Northeast = 1428),MW=Midwest = 1582),S=South (n = 1206), (n (n W=West = 1519);U/nd=Unsatisfactory/not (n done] Locus ABO Genotype 0 A1 NE 0.430 0.356 0.060 0.114 0.029 0.011 0.850 0.147 0.003 0.180 0.495 0.325 0.031 0.254 0.714 0.762 0.202 0.037 0.150 0.460 0.350 0.024 0.959 0.007 0.005 0.002 0.028 MW 0.410 0.358 0.071 0.115 0.032 0.012 0.859 0.141 0.000 0.175 0.510 0.315 0.030 0.259 0.711 0.780 0.203 0.017 0.179 0.470 0.325 0.010 0.967 0.020 0.003 0.000 0.010 S 0.463 0.334 0.081 0.093 0.016 0.012 0.829 0.167 0.004 0.165 0.484 0.350 0.037 0.266 0.696 0.719 0.249 0.031 0.152 0.464 0.321 0.035 0.947 0.011 0.007 0.001 0.034 W 0.474 0.353 0.062 0.083 0.019 0.008 0.846 0.152 0.002 0.188 0.512 0.300 0.027 0.294 0.679 0.754 0.225 0.021 0.171 0.475 0.320 0.018 0.966 0.011 0.005 0.000 0.018

B A1B A2B Rh-D

A2

D+ DCc cc EE Ee ee
CC

DU Rh-C

Rh-E

Secretor status

Se+ SeU/nd 1-1 2-1 2-2 U/nd CC BC DC Other U/nd

Haptoglobin

Transferrin

TABLE 3 the random distributions Yale Caucasian malestudents = 1000)versus stratified Genotype for (n sampleofCaucasianpopulation

Locus ABO

Genotype 0 A B AB

Yale 0.431 0.422 0.110 0.037

NE 0.430 0.416 0.114 0.040

MW 0.410 0.431 0.115 0.044

0.793 0.207

S 0.463 0.415 0.093 0.038

W 0.474 0.415 0.083 0.027

0.770 0.230

Secretor status

Se+ Se-

0.773 0.227

0.791 0.209

0.743 0.257

(1993), who analyzed these regionaldata using a that does not account diversity method partition to foundthat only0.4% ofthe diforsamplingerror, amonglocalitieswithinan ethnic versity occurred group. Contrastthis with Lewontinand Hartl's of of (1991) characterization the similarity the rein gional data: "vague claims ofthe similarity the
'shape' ofthe VNTR distribution... are irrelevant."

The FBI's database has been subjectto the most in criticism, large part because it is reputedto be of composedpredominantly FBI agents. (In fact,

about25% oftheCaucasian samplesare FBI agents.) It has been arguedthatanalysesdemonstrating the rarity DNA profiles of matches(Risch and Devlin, 1992a) were meaningless because theyinvolvethe FBI database. Thesecriticisms werebased onthebelief thatthereare large(genetic) differences between Caucasian FBI agents and the average Caucasian American (Geisser,1992). An analysisoftheVNTR data suggests otherwise. Comparing FBI agents the to the remainder the Caucasian database (blood of bank samples),no locus demonstrates significant a

DNA FINGERPRINTING:A REVIEW OF THE CONTROVERSY

241
0

allele distributions. between fixed-bin the difference for Figure6 plotsthe allele probabilities FBI agents two samplefor loci,D2S44 and againsttheremaining D4S139. the are It appearsthathumangeneticists correct: are sampling by databases constructed convenience randomsamples. reasonable proxiesforstratified Does this mean thatthe evaluationofDNA profiles Of considerations? from statistical couldnotbenefit coursenot. The regionaldatabases are-small and of subjectto substantialeffects sampling therefore differences. regional inherent as error, well as minor for It would seem that this is an ideal setting apBayes methods.A empirical plicationofideas from in scientist Minnesotamaywishto use her forensic from numerthe Minnesotadata, yetdrawstrength With aroundthe country. ous otherdatabases from of an estimate Osand an estimate thethesampling of of Bayes estimates allele frequencies error, empircal available. are directly

LOo W C) 7m-

~~~~0
o

<) ED

~~0
0 0

0 0

C)
Ur_ Or

0.0

0.05 0.10 0.15 Other Caucasians

C\J
'7-

~~~~~0
0 0 0

co
al)

<0) CD0 0D
0

0 00 00 inte tegop

remanin

6. CALCULATING I2kWITHOUT DECLARING A MATCH

CDuain

0.0

Other Caucasians

0.04

0.08

0.12

a Berry(1991) introduced methodforobtaining ?/JZ obviatesthe need to declare a match. In that on literature this Section6.1, I reviewthe current difa somewhat it motivating from perspective topic, of Methods thistypebypassthe from ferent Berry's. thereby method, stepofthematch/binning matching in a avoiding greatdeal ofargument the potentially Z9R in courts.Although, theory, : 0 forany profile, between in practice, whenthereare largedifferences Z2 fragments, R 0. Methodsbased on comparable of ratioenjoy some versions thelikelihood continuous in use in the United Kingdom. Unfortunately, the to calUnitedStates,theiruse is limited theoretical culationsand comparisons.
6.1 The Likelihood Ratio

FIG. 6. A plot of thefixed-binallele probabilities of D2S44 (top) and D4S139 (bottom) for a partition of the FBI's Caucasian database: this partition is all FBI agents in one group, and the remaining Caucasians in the othergroup.

and is population hencethelikelihood (21) lik(x7,x27yl IHo) = f(xl,x2) f( Yl,Y2). y2 UnderH1 the samplesmustbe from same allethe error les; theymaydiffer to measurement due only. Therefore
lik(x1,X2,y1,Y2jHi)

(22) the consider sinfor To deriveO2R VNTR data,first ofexposition, ignore gle locus case. For simplicity introduced coalescence. From the complications by that of the physicalproperties the data, it is known < A2,thenX1 < X2. Thisholds(approximately) ifA1 in the bivariatenormalmodel,too,because the correlationis large foralleles of similarsize. When X1 high probability < X2 (as in Figure2). Hencetake forth, convention, X1 to be thesmallerofthe by measurements. two and ( Y1,Y2)denotethe suspectand the Let (x1,x2) samples, respectively.Under Ho, the evidentiary the samples are obtainedas a randomdraw from
(X1,X2) are measurements of a(i) < a( j), then with

'y(i, j)q$ij(X1,X2)q5ij(yl,

Y2).

i?,j

Finally,
(23) C,R= lik(x1,X2,Y1,Y2HO) Pr(9e)

it is thanzero, is no error greater whenmeasurement clearwhether notthesampleshave matchor longer zero. and inggenotypes hence?2Zis neverprecisely the genotype To calculate ?1Z an estimateof -y, for is probability distribution, required. A method approximating likelihoodratio was pioneered the by Gjertson al. (1988) forpaternity cases using et

as the measurement errorgoes to zero. Notice that,

242

K ROEDER

VNTR's.A fewyearslatertheideas werefurther developedin threearticles(Berry, 1991; Berry, Evett and Pinchin,1992; and Devlin, Risch and Roeder, 1992). Devlin, Risch and Roeder (1992, subsequently DRR) take a direct modeling approach obtainthe to estimateof the genotype dismaximumlikelihood tribution, .). An approximatioin the likelihood -y(., to (,.) into(5) ratiois then obtainedby substituting and (22). Because theyassumethe alleles are independent, it suffices estimatethe allele distribution into and voke (1). This method requiresan estimateofthe location of the grid of alleles {a(k), k = 1,... ,m} k and the associated weights {-y(k), = 1,... ,m}. For the the VNTR'stheystudied, distancebetween supports a(k) - a(k - 1) is a known quantity, hence the supportcan be estimatedwithgreat accuracy. assume the supports For the purposeofexposition, {a(k), k = 1,... ,m} are known quantities. the r orLet (zlj < z2j), j = 1,... , r, represent of in deredpairs ofobservations fragment lengths a of reference population size r. Recall from that (4) of these measurements comprised allele pairs are errors E2)which with measurement are convolved (61, distributed. H-W assumedto be normally Assuming the measurement error and ignoring correlated (for -y of the purposeofestimating only),the likelihood is the data in thereference population thatofa normal mixture,
lik(y) = flfl Zy(k)
j=1 i=1 k=1

population witha bivariate normal kernel, obtaining a continuous estimateofthe genotype distribution. The genotype distribution estimated is by
H(u, V)=

E N (u zi

( (bc)z2

whereb is a smoothing parameter. The authors suggest that settingb = 1 accountsformeasurement error whilesetting > 1 accounts sampling b for variationas well [butsee Chernoff (1991) and DRRI. Berry, Evettand Pinchin (1992,BEP) estimate (21) with

ff q(Xx1, X2)dH(u, v)
U<V

2
U<V

q$uv(yl,y2)dH(u, v)

and (22) with 2

U<V Obuv(X1,X2)Ouv(Yi,

Y2)dH(u,v)

By assumingindependence acrossloci,the multilocus ZCR be obtainedby multiplying single can the locus?/Js obtained from either method.
6.2 Comparison and Performance

*exp - ~-2( [Zij- a(k)]2}. estimate -y uniqueand for is likelihood The maximum of are consistent.The properties this estimator exploredin Devlin, Risch and Roeder(1991b). For a of whatis theeffect estimating given genotype, CR(-y) that with CRQ(-)?As one wouldexpect,DRR found bethevarianceincreasedas the observed genotype the came morerare. Specifically, varianceincreased of as almostlinearly a function UJ(Q).Thishad little as interpracticaleffect, however, a 95% confidence to was continued be large if 2RQ(5) val about 04RQ5y) large. The DRR approachcouldalso be used to obtainan without assumdistribution estimate thegenotype of the of ingindependence alleles;however, varianceof increased,perhapsto (, ) would be substantially thepointofhavingpractical impact. Evett and Pinchin(1992) obtaina smooth Berry, estimateofthejoint distribution (A1,A2)by conof volvingthe pairs of observations the reference in

This subsection examinesthe performance the of ?/k. Bevariousstatistical methods calculating for cause ofthe tremendous in variability the populaof tion,?JR 10-15in thevast majority cases when < the DNA profiles tworandomly of selectedindividuals are compared, evenwithas fewas twoloci. For example,using the BEP methodand a three-locus system, Evett,Scranage and Pinchin(1993) found that,underHo, ?/ > 0 in onlyeightcases out ofa million while, underH1, ?JR typically largeas a is as million often largeas a billion.Similarresults and as wereobtained other for twoand three-locus systems Evett and Pinchin,1992; Devlin,Rischand (Berry, Roeder, 1992). The BEP and DRR methodsperform similarly, eventhough theyare mathematically quitedifferent in theirformulation. Whiletechnically is correct it to deconvolve (DRR) ratherthan convolve (BEP) to obtainan estimateof y, the DRR methodhas the of disadvantage havinga largervarianceand being morecomplicated than the BEP method.The BEP on method, the otherhand, reducesits varianceat the expenseofintroducing slightbias: it overestia of for matestheweight theevidence common phenotypesand underestimates weight theevidence the of for rarephenotypes.

DNA FINGERPRINTING:A REVIEW OF THE CONTROVERSY

243

In principlethe methodsdesignedfor continubetweenthe ous data are betterat discriminating than the match/binning hypotheses two competing of because theyavoidthe ambiguity declarmethod inga matchandhencehavezerochanceoffalsenegathe whenH1 holds, match/binning tives.In addition, one that is typically to leads to an estimateof ?JR smallerthanthevalue severalordersofmagnitude Evettand Pinchin, using(23) (Berry, obtained of?/R 1992;Evett,Scran1992; Devlin,Rischand Roeder, to age and Pinchin,1993). It is difficult compare methto method the continuous the match/binning use scientists ods when Ho holds because forensic to criteria declarematches. and objective subjective of to In an experiment assess the probability false of the tounderscore inadvisability the (and negatives objective to recommendation use strict NRC report's Evett,Scranage and Pinchin(1993) found criteria), witha matchwindowofthreestanmethod that a for declaresan exclusion 6% falsely dard deviations of the cases. Under Ho, theyalso foundthat the than methodwas less conservative match/binning matchcriobjective whena strictly the BEP method terionwas implemented:27 and 9 cases out of a and millionobtainedZ9/> 1 forthe match/binning criteria Usingsubjective respectively. BEP methods, from wouldbe removed manyofthesefalsepositives theNRC (Evett,1993). Unfortunately, consideration the denying matchcriteria, calls forobjective report judgment.In the absenceofexpert value ofexpert method an unnecesis the judgment, match/binning tool. sarilycrudestatistical

persons).Thisinvites unrelated related(henceforth, of a Whatconstitutesproof uniqueness? thequestion, by This questionis partlymotivated the suggesrule use tionthatthe courts the"one-on-N" (Lewontin and Hartl,1991); thatis, ifthe suspect'sprofile in does not matchany ofthe N profiles the appropresent thenthe courts population, priatereference thisarbehind 1/Ninsteadof1/02. The motivation Of goes as follows. theN possiblegenotypes gument the thathave beenobserved, suspectdoesnotmatch of the any ofthem;therefore, probability observing the in drawfrom population thisgenotype a random this as estimated 1/N. Contrast apis conservatively Supposewe know extreme. withtheopposite proach and that they that thereare n possiblegenotypes probare all equallyprobable.Thenthe appropriate by of any ability drawing givenprofile chancewould of in factbe 1/n. If profiles unrelatedpersonsare unique,thenn -* oo. have beenmadeto esSomepreliminary attempts are genotypes possiblefor timatehowmanydistinct of a givenbattery loci and how one mightevaluate the of an upperboundfor probability the mostcomIf of mongenotype. the number possiblegenotypes is enormous relativeto the populationand if none then abundant, is ofthe genotypes overwhelmingly near uniquenessamongunthis evidencesupports workin this area relatedindividuals.The original appears to be due to Risch and Devlin (1992a) and by study Herrin(1993). by was supported a careful in described Section3.5, Risch Using techniques of and Devlin(1992a) arguedthatthe number fivewas so large that the locus genotype-equivalents small. was vanishingly of probability a chancematch 7. OPEN ISSUES dependson theirchoiceof genotype-equivalent [The expanded rule-2.4%. Theysubsequently matching thathavenot a topics I In thissection, describe few rule to 5% (Risch and Devlin, 1992b) the matching These in coverage theliterature. extensive received and reachedthe same conclusion.]Whenindepencan topicsincludethe issue ofwhen DNA profiles acrossloci is assumed, denceofmatchprobabilities unique genomes,database be assumed to identify matchfor ofa five-locus probability theyestimated error. and laboratory to searching findsuspects, each oftheracial groupsstudieswas approximately as 10-12. If one were to considergenotypes dis7.1 Uniqueness of different genotypes crete entities,the number No twopeoplehave thesame set ofdermalfinger- must be at least as great as the inverse of the numberof genominimum matchprobability-the is by Thisfact relieduponroutinely thecourts prints. are the genotypes all are technically typeswouldoccuronlywhen despitethefactthatfingerprints only the to Another approach determining equallylikely. is of uniqueifa largeportion thepattern measured. whichdoes numberofdifferent patterns, genotype of (a In realityonlya small fraction the pattern set across loci, is to use the not relyon independence no is Likewise, twopeople of number points) verified. is This approach of genotypes. have the same genome(withthe possibleexception distribution observed ofunseen the ofidenticaltwins). Parallelingdermalfingerprints, similarto that ofestimating number and Corbet Williams, 1943)and gives species(Fisher, sequencingthe entiregenomeforany givencrime whichis 0(10)11. Fromthese analyses, an estimate someloci are is notfeasibleor necessary.Although easof it appearsthatthenumber possiblegenotypes than others(Devlin, moreinformative considerably size. Theyalso ilyexceedsthe totalU.S. population Risch and Roeder,1992), much evidencesuggests to the mostcommon obtaineda crudeupperbound to maybe variableenough aplocusprofiles thatfive 10-6. of genotype approximately proachuniquenessforpersonswho are not closely

244

K ROEDER

issues I have now covered manyofthe statistical in use inherent theforensic ofDNA. As I summarized of in Section2.4, a committee theNationalResearch discussedmanyofthe same Council(NRC) recently there 1992report. Unfortunately were issuesintheir a on even no statisticians thecommittee, though main of was statistical nature.The jor focus thereport minor werenumerous of consequences thisomission and statistical and majorerrors theory inis an open question. regarding whichare of results, genetic terpretation population nowhavingan impacton thejudicial process(Har7.2 Laboratory Error the mon,1993). I willsummarize keyissues covered of inthisreview contrasting interpretationthe my by errorto have ocHere we considera laboratory voiced with interpretation the data andtheliterature two samplesto deof comparing curredif,instead bytheNRC panel. if termine theymatch,the same sample was accibased dismissesthe statistically The NRC report case, inanalyzedtwice. For a particular dentally of likelihoodratio methods(Section 6) as Bayesian the is formation available thataffects probability to that wouldbe unacceptable the courts, documentation, methods a handlingerror: chain of custody devised binning methods insteadthematch favoring analyzed,variousconprofiles numberof different (Section 2.3). Thereport byforensic scientists nmisses information. trolsand otherbiological

of portions thisexperiment (1993) repeated Herrin analyzedthe efwithotherdatabases. He carefully allowingit to extendup fectofthe matchwindow, of to 20%. The effect this was a drasticincreasein he of the probability matches. Nevertheless, estiis mated that the numberof genotype-equivalents large. extremely open remains of of The question a proof uniqueness of on and dependsstrongly thecomplications relatedness amongindividuals.The analysesofRischand (1993) are ofunrelated Devlin(1992a, b) and Herrin only. individuals discussedin Secthe On a relatedtopic, methods based on tion2 applywhenthe suspectwas selected if is By evidence. contrast, a suspect idennongenetic a evidenceobtainedfrom DNA tified onlythrough of data bank,wherea multitude individuals profile on have theirDNA profiles file(analogousto dermal issues arise. Bedata fingerprint banks),additional unique,the are cause DNA profiles not considered carefully. data mustbe interpreted court cases,for Similarissues have arisenin other instance,the Collinscase; fordetails,see Solomon solely (1982). In this case, a suspectwas identified based on the factthat he had a numberof charwiththe culprit(e.g., model in acteristics common This situation differs from and colorofautomobile.) cases wherethe DNA is foundto match,afterthe usingotherevidence.It suspecthas been identified in probability this has been arguedthattherelevant of a is not the probability observing suspect case due to as withthe same characteristics the culprit is calculation the appropriate chancealone. Rather, exone moreindividual that theprobability atleast whohas the characists in the reference population has ofthe culprit, giventhatan individual teristics withthosecharacteristics. alreadybeen observed has Instanceswherea database ofDNA profiles arisen havealready to beensearched obtaina suspect In IllinoisandVirginia. theMinnesota in Minnesota, used to searchthedatabase the DNA evidence case, was not enteredinto court. This approach,while by conservative (and recommended theNRC report), The fulluse ofthe information. apdoes not make to solution thistypeofproblem statistical propriate

researchon Therehas been verylittlestatistical errorrates. The emphasishas been on laboratory thereis littleinformatesting.Actually proficiency testing, and what littleexistsis tionon proficiency For example,consider misinterpreted. frequently the error ratesfor California the data on laboratory AssociDirectors tests(California CrimeLaboratory 1988). Based Directors, ationofCrimeLaboratory thatone laborasuggested on thesetests,it is often error rate is 1/50 = 0.02 (e.g.,Geisser,1992). tory's It is true that 50 samples were sent to each testhad and inglaboratory, thatonelaboratory onefalse the so however, testswerestructured thatthe match; for had laboratory to drawan inference all possible of pairwisecomparisons the50 samples.Even ignorto of difficulty thesetests,compared ingthe greater thislab ratefor thestandard forensic case,theerror indeed wouldbe 1/1225 < 0.0008 ifthe laboratory made all possiblecomparisons. testingis I believethis emphasison proficiency conmisplaced. A greatdeal ofusefulinformation rates understandardconditions laboratory cerning suit of is availableintheform paternity data. In situto testing ationswhereitis impossible do proficiency methods of disaster), (e.g.,probability a spaceshuttle relatederror for have been developed incorporating (e.g.,Hartigan1990). Preratesintothe calculation incouldbe constructed which a by sumably method from error ratesin paternity testing, proformation to and specific the case testing, information ficiency of to probability a couldbe combined form posterior for case. error a particular a handling REMARKS:CONTRASTING 8. CONCLUDING OF THE VIEWPOINTS A STATISTICIAN ANDTHE NRC PANEL

DNA FINGERPRINTING:A REVIEW OF THE CONTROVERSY

245

methods simply yielddisthepointthatthebinning ratio(Section to cretized approximations a likelihood (Section6.2). 2.1) that are somewhatless efficient matching is a sourceofcontention rule The arbitrary that in mostcases that cometo trial. I recommend vera the courtsmovetowardadopting continuous about argument sionofZUR as toavoidunnecessary so matching. DNA proof To evaluatethesignificance matching the a principle, the recommends ceiling files, report of methoddesignedto be independent the heritage ofthe suspect (Section2.4). This is not a satisfyproblem.If the suspect to ing solution this complex and evidentiary samplecan be assumedto be drawn of then independently, it is the population possible theheritage the suspect, of thatis not perpetrators, relevant(Section4.1). Even ifthe suspectand culthereare better ways pritare assumedtobe related, to adjust the calculationthan the ceilingprinciple (Sections4.2 and 4.3). of for The othermotivation the ceilingprinciple In fact, is heterogeneity. match/binning population has populationheterogeneity been the crux ofthe the about quantifying weightofthe eviarguments of heterogeneity dence. One consequence population amongeventscomis that it leads to dependencies con(Section4.2). Another prisinga VNTR profile will sequence is that some DNA profiles tendto be than morecommon theircognatesubpopulation in in the mixedpopulation (Sections3.1 and 4.2). the reheterogeneity, report population Regarding of lies on onlyone study.Based on the findings this claimedthatthereare larger the study, NRC report betweenindividualsof British, geneticdifferences thanthereare between Frenchand Italian heritage Caucasian and OriAmerican, individuals African of about human ental heritage. This curiousfinding resultsis based on a 1972 studythatused genetics thatdid not a method partition to geneticdiversity and is inherently biased accountforsamplingerror sucha result (Section 5.1). Moreretoward providing the is centstudiesdemonstrate opposite true:there Cauis greaterdiversity Americans, amongAfrican is but casians and Orientals, this diversity dwarfed (Section5.1). The conseby individualvariability threeor obtainedfrom quence is that DNA profiles moreloci are rare in all ethnicgroups.Exactlyhow rare depends somewhaton the choiceof reference population. For instance,the range may span one but such a rangewill to two ordersof magnitude, as have littlepracticalimpacton ?LJ's large as several million. of also are indicative Violationsofindependence populationheterogeneity.Tests of independence from (Secindependence detect deviations any rarely signifiwhenstatistically tions3.2-3.5). Moreover, do theyfrequently not cant deviations observed, are

lead to deviationsof practicalimportance (Section 3.6). The reportargues,based on a two-allelelocus,thatstatistical testsofindependence power lack to detectdependencies inducedby populationsubstructure. fact, In such tests(Sections3.2 and 3.5), whilenot sensitive weak dependencies, powto are erful mixture if inducesmeaningful differences between truegenotype frequencies thoseestimated and assuming independence. Finally, statistical methods accountforany exto istingheterogeneity readily are developed spring and from naturally population genetictheory (Sections 3.1 and 4.2). I recommend that corrections, when be necessary, based onpopulation genetic and statistical theory. hoc corrections Ad such as the ceiling are principle difficult justifyand sometimes to obtheneed for scure sensiblecorrections such as those in described Section4.3 wherethe suspectand culpritare assumedto be closerelatives. It is myhope that this reviewhas informed the readeraboutthemajorstatistical issues in thisarea, as well as theresults.Open statistical issues on the forensic ofDNA exist(Section7), and others use will becomeobviousas the technologies and databases to continue evolve. ACKNOWLEDGMENTS I would like to thank Bernie Devlin, Ian Evett, Jay Kadane, JohnHartigan and the Editor,Rob on of comments a previous draft the Kass, for helpful John manuscript; Ivan Balazs and Bruce Hartmann, Budowleforthe use oftheirdata; and Ivan Balazs, BruceBudowle and Rockne Harmon comments for on of a draft myrejoinder. This research was supported and DMS-92-57006. byNSF GrantsDMS-92-01211 REFERENCES
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