Comprehensive mutation analysis of 17 Y-chromosomal short tandem repeat polymorphisms included in the AmpFlSTR® Yfiler® PCR amplification kit

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  Comprehensive mutation analysis of 17 Y-chromosomal short tandem repeat polymorphisms included in the AmpFlSTR® Yfiler® PCR amplification kit
  ORIGINAL ARTICLE Comprehensive mutation analysis of 17 Y-chromosomalshort tandem repeat polymorphisms includedin the AmpF l  STR® Yfiler® PCR amplification kit Miriam Goedbloed  &  Mark Vermeulen  &  Rixun N. Fang  &  Maria Lembring  & Andreas Wollstein  &  Kaye Ballantyne  &  Oscar Lao  &  Silke Brauer  &  Carmen Krüger  & Lutz Roewer  &  Rüdiger Lessig  &  Rafal Ploski  &  Tadeusz Dobosz  &  Lotte Henke  & Jürgen Henke  &  Manohar R. Furtado  &  Manfred Kayser Received: 13 August 2008 /Accepted: 13 March 2009 /Published online: 26 March 2009 # The Author(s) 2009. This article is published with open access at Abstract  The Y-chromosomal short tandem repeat (Y-STR) polymorphisms included in the AmpF l  STR® Yfiler® polymerase chain reaction amplification kit have becomewidely used for forensic and evolutionary applicationswhere a reliable knowledge on mutation properties isnecessary for correct data interpretation. Therefore, weinvestigated the 17 Yfiler Y-STRs in 1,730  –  1,764 DNA-confirmed father   –  son pairs per locus and found 84sequence-confirmed mutations among the 29,792 meiotictransfers covered. Of the 84 mutations, 83 (98.8%) weresingle-repeat changes and one (1.2%) was a double-repeat change (ratio, 1:0.01), as well as 43 (51.2%) were repeat gains and 41 (48.8%) repeat losses (ratio, 1:0.95). Mediansfrom Bayesian estimation of locus-specific mutation rates Int J Legal Med (2009) 123:471  –  482DOI 10.1007/s00414-009-0342-y Electronic supplementary material  The online version of this article(doi:10.1007/s00414-009-0342-y) contains supplementary material,which is available to authorized users.M. Goedbloed :  M. Vermeulen : M. Lembring : A. Wollstein : K. Ballantyne :  O. Lao :  S. Brauer  :  M. Kayser ( * )Department of Forensic Molecular Biology,Erasmus University Medical Center Rotterdam,PO Box 2040, 3000 CA Rotterdam, The Netherlandse-mail: m.kayser@erasmusmc.nlR. N. Fang : M. R. FurtadoResearch Division of Applied Markets, Applied Biosystems, Inc.,Foster City, USAM. LembringBiology Education Centre, Uppsala University,Uppsala, SwedenA. WollsteinCologne Center for Genomics and Institute of Genetics,University of Cologne,Cologne, GermanyS. Brauer The Netherlands Forensic Institute,Den Haag, The NetherlandsC. Krüger  : L. Roewer Abteilung für Forensische Genetik, Institut für Rechtsmedizin undForensische Wissenschaften, Charité  –  Universitätsmedizin Berlin,Berlin, GermanyR. LessigInstitut für Rechtsmedizin, Universität Leipzig,Leipzig, GermanyR. PloskiDepartment of Medical Genetics, Medical University Warsaw,Warsaw, PolandR. PloskiDepartment of Forensic Medicine, Medical University Warsaw,Warsaw, PolandT. DoboszDepartment of Forensic Medicine, Wroclaw Medical University,Wroclaw, PolandL. Henke :  J. HenkeInstitut für Blutgruppenforschung LGC GmbH,Köln, Germany  Present Address: M. LembringDepartment of Genetics and Pathology, Rudbeck Laboratory,Uppsala University,Uppsala, Sweden  ranged from 0.0003 for DYS448 to 0.0074 for DYS458,with a median rate across all 17 Y-STRs of 0.0025. Themean age (at the time of son ’ s birth) of fathers withmutations was with 34.40 (±11.63) years higher than that of fathers without ones at 30.32 (±10.22) years, a differencethat is highly statistically significant (  p <0.001). A Poisson- based modeling revealed that the Y-STR mutation rateincreased with increasing father  ’ s age on a statisticallysignificant level ( α =0.0294, 2.5% quantile=0.0001). Fromcombining our data with those previously published,considering all together 135,212 meiotic events and 331mutations, we conclude for the Yfiler Y-STRs that (1) nonehad a mutation rate of >1%, 12 had mutation rates of >0.1%and four of <0.1%, (2) single-repeat changes were stronglyfavored over multiple-repeat ones for all loci but 1 and (3)considerable variation existed among loci in the ratio of repeat gains versus losses. Our finding of three Y-STR mutations in one father   –  son pair (and two pairs with twomutations each) has consequences for determining thethreshold of allelic differences to conclude exclusionconstellations in future applications of Y-STRs in paternitytesting and pedigree analyses. Keywords  Y-STR .Mutation.Microsatellites.Y-chromosome.AmpFlSTRYFilerkit  Introduction A reliable knowledge of the particular Y-chromosomalshort tandem repeat (Y-STR) polymorphisms used in theforensic context is essential for the correct interpretation of the resulting profiles. Over the last years, 17 Y-STRsincluded in the commercially available AmpF l  STR®Yfiler® polymerase chain reaction (PCR) amplification kit (Applied Biosystems, Inc., Foster City, CA, USA) have become widely used in the forensic genetic community aswell as for evolutionary anthropological studies. Establishinga reliable knowledge on the mutation rates and characteristicsofthese particular17Y-STRsincludedinthe kit are important for particular forensic and anthropological applications. Inforensics,mutation rates are neededwhenSTRs are applied to paternity testing, and Y-STRs are especially powerful indeficiency cases of disputed paternity involving male off-spring where the alleged father is not available for DNAanalysis but is replaced by any of his male paternal relatives.In such applications, the knowledge on Y-STR mutation ratesneeds to be considered in the paternity probabilities, andmutations are more likely the more generations the son isseparated from its putative male paternal relative [1]. There are also other forensic applications where Y-STR mutationrates have to be considered, i.e., all those that includedifferent members of the same male lineage. In evolutionaryanthropological studies, Y-STRs are usually applied to unveilthe local and temporal origin of a given Y-SNP basedhaplogroup, and Y-STR mutation rates are used for timeestimations as well as (often) for weighted network con-structions [2]. In addition, Y-STRs are useful in genealogical studies where mutation data are needed as well [3]. There are several approaches to establish Y-STR mutation rates including genotyping father   –  son pairs fromtrio cases of autosomal DNA confirmed paternity [4], malesfrom deep-rooted pedigrees [5], single sperm cells or small  pools of sperm cells [6], or using Y-STR population data in combination with known historical events for time calibration[7]. Of these, studying DNA-confirmed father   –  son pairs isthe most reliable approach but only if the number of father   –  son pairs investigated is large enough to reveal reliablemutation rate estimates. This is because mutation rates of STRs, including Y-STRs, are expected to be small (about one mutation in 1,000 generations per locus). It is thereforeimportant to further increase the number of father   –  son pairstyped for the specific Y-STR loci intended to be applied for forensic and evolutionary analyses to provide more reliableknowledge about their mutability and thus to further gaincertainty in Y-STR data interpretation.Several studies have investigated mutation rates andcharacteristics of Y-STR loci widely used in forensic,genealogical, and evolutionary studies [4,5,8  –  23]. However,the mutation information for some of the Y-STRs included inthe Yfiler kit is still very limited as most of the Y-STR mutation rate studies so far were conducted on a subset of markers included in Yfiler kit (e.g., the nine Y-STRs definingthe so-called minimal haplotype). Only six previous studiesinvestigated the complete set of 16 Yfiler Y-STR loci(DYS385a/b was considered jointly) in father   –  son pair analyses covering all together only 1,624 meiotic transfers per single locus [16,18,19,21  –  23]. In this paper, we report mutation data for the 17 Y-STRs included in theAmpF l  STR® Yfiler® PCR amplification kit from analyzing1,730  –  1,764 father   –  son pairs per locus, comprising a total of 29,792 meiotic transfers (mutations at DYS385a andDYS385b were analyzed separately) and representing thelargest single Yfiler mutation study available thus far. Weadditionally provide summarized mutation data from our study and previously published data for the same 16 Y-STR loci(DYS385a/b considered ascombinedsystem) comprising3,531  –  11,900meiotictransfers per eachoftheY-STRloci(alltogether 135,212 meiotic transfers). Materials and methods Father   –  son pair samples used in this study were confirmedin their family relationship by DNA analysis using varioussets of DNA markers before this study, and all had paternity 472 Int J Legal Med (2009) 123:471  –  482   probabilities of >99.9%. Samples came from five samplingregions: Cologne, Leipzig, and Berlin in Germany as wellas Warsaw and Wroclaw in Poland. Individuals came fromthe named cities as well as their surrounding regions, i.e., provinces/counties these cities are part of. Although thevast majority will have originated from the respectivegeographic regions, we cannot exclude some migrants fromother regions. If known, individuals of origin fromcountries other than those considered in the respectiveregional sample sets were excluded from the study. There isno sample overlap between the present study and our  previously published mutation study [4]. Because of verylow DNA quantities available for the Leipzig samples, awhole genome amplification procedure was performed before Yfiler PCR analysis using the GenomiPhi DNAAmplification Kit (GE Healthcare, Little Chalfont, UK).One or 5 µl (depending on DNA concentration) genomicDNA were added to 9 µl of sample buffer and denatured at 95°C for 3 min, then cooled on ice. Subsequently, 9-µlreaction buffer plus 1 µl of enzyme mix were added to thecooled sample and incubated at 30°C for 16  –  18 h, then heat inactivated at 65°C for 10 min. Afterwards, the whole-genome-amplified DNA was purified using Invisorb® 96Filter Microplates (Invitek GmbH, Berlin, Germany).The Y-STRs included in the AmpF l  STR® Yfiler® PCR amplification kit (Applied Biosystems, Inc.): DYS19,DYS389I, DYS389II, DYS390, DYS391, DYS392,DYS393, DYS385a/b, DYS437, DYS348, DYS439,DYS448, DYS456, DYS458, DYS635, and Y-GATA-H4were genotyped according to the instructions provided by themanufacturer and using a gold-plated silver block GeneAmp®PCR System 9700 (Applied Biosystems, Inc.).All PCRs, except for the Berlin samples, were carried out at the Department of Forensic Molecular Biology, Erasmus MCRotterdam (The Netherlands), and after quality control, PCR  products were shipped on dry ice to Applied Biosystems at Foster City (USA), where fragment length analyses was performed using the 3130  xl   genetic analyzer according to theguidelines in the AmpF l  STR® Yfiler® PCR amplification kit user manual.Yfilerprofiles were generatedusingGenemapper ID v3.2 software (Applied Biosystems Inc.), and generated profiles were manually inspected by experienced techniciansin Rotterdam for quality control. The Berlin samples weregenotyped at the Abteilung für Forensische Genetik, Institut für Rechtsmedizin und Forensische Wissenschaften, Charité(Germany) according to the manufacturer  ’ s instructions.Genotype differences between respective fathers and sonswere identified using in-house developed MATLAB®-scriptsusing version (The MathWorks, Inc., Natick, MA,USA).All mutations were confirmed by DNA sequenceanalysis of the respective father and son DNA sample at the respective Y-STR locus in Rotterdam. Mutations at the DYS385a/b system were sequenced separately for DYS385a and DYS385b as described elsewhere [24]. Before DNA sequence analysis, PCR was carried out usingthefollowingconditions:10  –  20nggenomicDNAwasusedina total volume of 20  μ  l PCR reaction. Final concentrationswere 1× PCR GeneAmp PCR gold buffer and 0.5  –  1 unit AmpliTaq Gold (Applied Biosystems Inc.), 1 mM deoxyri- bonucleotide triphosphates (dNTPs; Roche DiagnosticsGmbH, Mannheim, Germany), 250 nM of each primer (seeSupplementary Table S1 for primer sequences used for sequencing as well as for PCR before sequence analysis)and 1.5  –  2.5 mM MgCl 2  depending on the marker. DYS393,DYS439 (2.5 mM MgCl 2 ), GATA-H4, DYS385a, andDYS385b (1.5 mM MgCl 2 ) were amplified using a 60  –  50-touchdown protocol: 95°C 10 min, ten cycles, 94°C 30 s,60  –  1°C 30 s, 72°C 45 s; 25 cycles, 94°C 30 s, 50°C 30 s,72°C 45 s, and final extension at 72°C 10 min. Thecombined DYS389I/II fragment was amplified using a 60  –  55 touchdown protocol: 95°C 10 min, five cycles, 94°C 30 s,60  –  1°C 30 s, 72°C 45 s; 30 cycles, 94°C 30 s, 55°C 30 s,72°C 45 s, and final extension at 72°C 10 min. DYS437,DYS392, DYS438, DYS19, DYS456 (all 2.0 mM MgCl 2 ),and DYS390 (2.5 mM MgCl 2 ) were amplified with a 65  –  50touchdown protocol; 95°C 10 min, 15 cycles, 94°C 30 s, 65  –  1°C 30 s, 72°C 45 s; 20 cycles 94°C 30 s, 50°C 30 s, 72°C45 s, and final extension at 72°C 10 min. DYS635 (1.5 mMMgCl 2 ) and DYS391 (2.0 mM MgCl 2 ) were amplified usinga 70  –  50 touchdown protocol: 95°C 10 min, 20 cycles, 94°C30 s, 70  –  1°C 45 s, 72°C 1 min; 15 cycles, 94°C 30 s, 50°C45 s, 72°C 1 min, and a final extension at 72°C 10 min.DYS458 (1.5 mM MgCl 2 ) was amplified using a fixedannealing temperature of 60°C; 95°C 10 min, 35 cycles,94°C 30 s, 60°C 30 s, 72°C 45 s, then a final extension at 72°C 10 min. DYS385a and DYS385b were amplifiedseparately as described elsewhere [24]. Excess of PCR   primers and dNTP was removed via enzymatic treatment of exonuclease I (Exo) and shrimp alkaline phosphatase (SAP)using the ExoSAP-IT ™  Kit (USB Corporation, Cleveland,OH, USA) where 5  μ  l PCR product was incubated with 2  μ  lExoSap-IT mix for 15 min at 37°C and inactivated at 80°Cfor 15 min, then cooled to 15°C for 5 min. DNA sequenceanalysis was performed via cycle sequencing in a totalvolume of 10  μ  l using the BigDye Terminator CycleSequencing Ready Reaction kit (Applied Biosystems Inc.)and the following conditions: 1  μ  l ExoSAP-IT-treated PCR  product, 1.5  μ  l sequencing buffer (Applied Biosystems Inc.),1.0  μ  l BigDyeTerminator v1.1 (Applied Biosystems Inc.),5 pmol of sequencing primer (see Supplementary Table S1for sequences) and LiChrosolv water (Merck KGaA,Darmstadt, Germany). The cycle sequencing was performedin an MJ-Research PTC-200 (Bio-Rad, Hercules, CA, USA) by heating to 96°C for 1 min, then 25 cycles of 96°C 10 s,50°C for 5 s and 60°C for 4 min and subsequent cooling to Int J Legal Med (2009) 123:471  –  482 473  15°C. The sequencing products were purified using 96-wellmultiscreen plates (Millipore, Billerica, MA) filled withSephadex G-50 superfine (GE Healthcare Bio-Sciences AB,Uppsala, Sweden) absorbed with LiChrosolv water (Merck KGaA). After spinning the column for 5 min at 2900 rpm,10  μ  l sequencing product was added to the column andcollected in a clean 96-well PCR plate after centrifugationfor 5 min at 2900 rpm. To the purified product, 5  μ  l HiDiformamide (Applied Biosystems Inc.) was added and loadedon the ABI 3100 Genetic Analyzer (Applied BiosystemsInc.). Separation of the purified sequencing products was performed using capillary electrophoresis under standardconditions. DNA sequences were aligned using the DNAstar software (DNASTAR, Inc., Madison, WI, USA). Since Y-STR typing was performed by Yfiler chemistry using labeled primers and therefore DNA sequencing was performed froman independent PCR reaction, our confirmation procedurethus included two independent analyses: one Yfiler fragment-length analysis and one sequence analysis. Y-STR mutations were only accepted as such if the repeat countsfrom the DNA sequence analysis matched the repeat-basedallele nomenclature of the Yfiler fragment length analysis.For additional confirmation, we included for all Y-STRssequenced control DNA samples that had known size andrepeat-based alleles from multiple Yfiler fragment lengthanalyses as well as known repeat counts from multiplesequence analyses as performed previously.Mutation rates were estimated by means of two different approaches: a frequentist approach and a Bayesian ap- proach. Frequentist estimation of the mutation rates wasconducted by dividing the number of sequence-confirmedmutations by the number of father   –  son pairs for every Y-STR locus and for every sampling region separately. Ninety-five percent confidence intervals of the mutationrates were established by using a binomial model given thetotal number of working father   –  son pairs and the estimatedmutation rate and obtained via the website To test for locus-specific differences in themean of the mutation rates between sampling regions(Cologne, Leipzig, Berlin, Warsaw, and Wroclaw), a permutation analysis was carried out. In each iteration,each father   –  son pair was assigned at random to eachsampling region, keeping the original population samplesize. The average mutation rate computed for the permu-tated populations was then compared with the observedrate, and the number of times that the permutated averagedmutation rate was larger than the observed one wasrecorded. The one tail  p  value was obtained by dividingsuch numbers by the 100,000 iterations that were conductedfor each locus. Overall mutation rate distributions collectedfrom the present as well as previous studies were estimated by means of a binomial hierarchical Bayesian model [25]  by using the Marcov Chain Monte Carlo (MCMC) Gibbssampling implemented in WinBUGS [26]. A non- informative prior normal distribution ( μ =0,  σ =1.0E − 06)was specified to estimate the logit of the overall mutationrate and a prior gamma distribution with parameters  α =1.0E − 5, and  β  =1.0E − 5 for the parameter tau as suggestedin WinBUGS. Three different Gibbs MCMC chains weregenerated when estimating the mutation rate for each locus,and 100,000 runs were performed for each chain. Mean,median, and 95% credible intervals (CI) were estimatedfrom the three chains after discarding the first 50,000 runsand performing a thinning of 15 in order to reduce theamount of autocorrelation (representing a final number of 9,999 retained runs). Bayesian estimations of DYS385a andDYS385b separately (as only available from our ownstudy) were performed by using a binomial model with auniform prior, which led to a posterior Beta distribution[25] with parameters  α = m +1 and  β  = n +1, where  m  is thenumber of mutant father   –  son pairs and  n  is the number of non-mutant father   –  son pairs. The ratio of repeat gainsversus losses and the ratio of single- versus multi-repeat changes were estimated using a multinomial-logisticBayesian model. For the individual studies, the relativelylow number of observed counts of each class required usinginformative priors, which highly skewed the posterior distributions towards the prior distributions, and credibleintervals tended to be large, including the 1:1 ratio (resultsnot shown). Therefore, we did not use the Bayesianapproach for such estimations. The ages (at the time of son ’ s birth) of fathers with and without mutations werecompared with a Mann  –  Whitney  U   test. The estimation of the effect on the mutation rate of the age of the father wascalculated by means of a Bayesian approach. Mutation ratewas modeled as a function of each age class using aPoisson distribution:  p y j q  ð Þ¼ Y nt  ¼ 1 1  y i !  x i q  ð Þ  y i e   x i q  where  θ  is the mutation rate,  y i  is the number of mutations,and  x i  is the number of father   –  son pairs for the age class  i .  θ is assumed to be dependent on the age of the father, with q   ¼ e a  a i þ g  , where  α  is the slope of the function, and  g   is theerror associated. If the mutation rate  θ  is independent of thefathers ’  age,  α  will be zero. Prior distributions for each parameter were ascertained in order to be non-informative: a    Normal  m ; s  a  ð Þ g     Normal 0 ; s  g     m   Normal 0 ; 1000000 ð Þ s  a    Gamma 0 : 000001 ; 0 : 000001 ð Þ s  g    Gamma 0 : 000001 ; 0 : 000001 ð Þ 474 Int J Legal Med (2009) 123:471  –  482  Results and discussion Y-STR mutation characteristicsWe investigated all together 29,792 meiotic events fromanalyzing 17 Y-STRs included in the AmpF l  STR® Yfiler®PCR amplification kit (DYS19, DYS389I, DYS389II,DYS390, DYS391, DYS392, DYS393, DYS385a,DYS385b, DYS437, DYS348, DYS439, DYS448,DYS456, DYS458, DYS635, and Y-GATA-H4) in 1,730  –  1,764 (per locus) father   –  son pairs of DNA-confirmed biological paternity. Note that, although DYS385a/b wasgenotyped jointly as part of the Yfiler kit, mutationconfirmation was performed separately for DYS385a andDYS385b (see Materials and methods), providing mutationrates separately for both DYS385 loci. We identified 84mutations that were all confirmed by DNA sequence analysis(Table 1, Supplementary Table S2). These 84 mutations were found among 16 Y-STRs, and no mutation was observed for DYS448 among 1,746 meiotic transfers studied. Single-repeat changes were observed for 83 (98.8%) mutations,whereas one (1.2%) mutation (at DYS438) was a double-repeat change [ratio=1:0.01; 95% binomial confidenceinterval (CIL), <0.006  –  1:0.037]. Among the 84 mutations,about the same number of repeat gains with 43 (51.2%) andrepeat losses with 41 (48.8%) were found (ratio=1:0.95;95% CIL 1:1.47  –  1:0.61; Table 1, Supplementary Table S2). Double-copy alleles either in the father or in the sonwere involved in two of the 84 mutations (see SupplementaryTable S2). For the only mutation found at DYS438, weobserved a slippage mutation from two equal-sized alleles(12) in the father to two alleles with two repeat differences(ten and 12) in the son. For one of the mutations at DYS635,there was a slippage mutation from one of two differentlysized alleles (23 and 24) in the father to two equal-sizedalleles (23) in the son. However, although these two father   –  son pairs were sequenced at both loci to confirm themutations (as all other 82 mutations were confirmed byDNA sequence analysis), which allowed identification of thetwo partially overlaying sequences in the two different-sizedalleles per individual, this confirmation test cannot rule out the possibility of an alternative deletion polymorphism in thecase of the DYS635 mutation. In addition, double-copyalleles in both father and son as result of a locus duplicationwith subsequent slippage mutation in previous generationswere found at DYS19 in three of the 1,757 father   –  son pairsinvestigated (two pairs with 15,16 and one pair with 15,17) but not at any other Y-STR locus investigated in this study.Double alleles at Y-STRs that usually exist in single copieswere previously observed especially for DYS19 but also for several other Y-STR loci included in the Yfiler kit [23,27  –  29]. They represent larger duplication events, including therespective Y-STR locus with subsequent Y-STR slippagemutations that length-differentiate the two (or more) Y-STR alleles. A recent study investigated the structural basis and phylogenetic relationship of DYS19 duplications in detail[30].Inherited null alleles in both father and son wereobserved in three cases and at two Y-STRs (DYS448, oneout of 1,746 pairs; DYS456, two out of 1,760 pairs) as aconsequence of a locus deletion or, alternatively, mutation(s) in the primer-binding sites. Null alleles at these andseveral other Yfiler Y-STRs were also observed in previousstudies [23,27  –  29,31,32] and were especially investigated recently for DYS448 where both phenomena, mutations inthe primer binding sites as well as deletions (includingsmall deletions that caused apparent double alleles at another YSTR, which we did not observe in the DYS448null allele observed in this study) were found to provide themolecular explanation [33].Y-STR mutation ratesIt seems to be the convention that mutation counts andfather   –  son pair counts are used for simple frequencyestimation of mutation rates and characteristics ( “ frequentist approach ” ) in individual studies but, moreover, also whenconsidering data from several independent studies[10,17,21,23,34]. However, there is an alternative way of  modeling such data in order to incorporate the uncertaintyof the estimation obtained by each study and also toestimate the meta-parameters of interest (i.e., the mutationrate) when considering data from multiple studies. This is ageneral issue in meta-analysis, which has been successfullysolved in areas outside the forensic mutation field [25]. For  a more realistic consideration of the uncertainty of the data,we have applied such an approach for mutation rateestimation from our own data as well as to combine thedata from our study with those from the 18 previous studies[4,5,8  –  23] using a hierarchical Binomial Bayesian model( “ Bayesian approach ” ; see  “ Materials and methods ”  for details). In our new data, medians from Bayesian estimationof the locus-specific mutation rates ranged from 0.0003(95% CI, 0.00003  –  0.0015) for DYS448 to 0.0074 (95% CI,0.0044  –  0.0117) for DYS458, with a median mutation rateacross all 17 Y-STRs of 0.0025 (95% CI, 0.0016  –  0.0034;Table 1). These estimates are based on pooled data per Y-STR locus, as we did not find any statistically significant differences in the locus-specific mutation rates between thefive sampling regions (  P  >0.05).To provide overall locus-specific mutation rates andcharacteristics that can be applied to forensic and evolu-tionary studies, we collected mutation data for the same 16Y-STRs from 18 previously published studies that analyzedDNA-confirmed male families [4,5,8  –  23] and combinedthose with our new data (Table 2). Note that since previous Int J Legal Med (2009) 123:471  –  482 475
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