Dataset Information

Mutation rate estimates for 110 Y-chromosome STRs combining population and father-son pair data.

ABSTRACT: Y-chromosome microsatellites (Y-STRs) are typically used for kinship analysis and forensic identification, as well as for inferences on population history and evolution. All applications would greatly benefit from reliable locus-specific mutation rates, to improve forensic probability calculations and interpretations of diversity data. However, estimates of mutation rate from father-son transmissions are available for few loci and have large confidence intervals, because of the small number of meiosis usually observed. By contrast, population data exist for many more Y-STRs, holding unused information about their mutation rates. To incorporate single locus diversity information into Y-STR mutation rate estimation, we performed a meta-analysis using pedigree data for 80 loci and individual haplotypes for 110 loci, from 29 and 93 published studies, respectively. By means of logistic regression we found that relative genetic diversity, motif size and repeat structure explain the variance of observed rates of mutations from meiosis. This model allowed us to predict locus-specific mutation rates (mean predicted mutation rate 2.12 × 10(-3), SD=1.58 × 10(-3)), including estimates for 30 loci lacking meiosis observations and 41 with a previous estimate of zero. These estimates are more accurate than meiosis-based estimates when a small number of meiosis is available. We argue that our methodological approach, by taking into account locus diversity, could be also adapted to estimate population or lineage-specific mutation rates. Such adjusted estimates would represent valuable information for selecting the most reliable markers for a wide range of applications.

SUBMITTER: Burgarella C

PROVIDER: S-EPMC3039515 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mutation rate estimates for 110 Y-chromosome STRs combining population and father-son pair data.

Burgarella Concetta C Navascués Miguel M

European journal of human genetics : EJHG 20100908 1

Y-chromosome microsatellites (Y-STRs) are typically used for kinship analysis and forensic identification, as well as for inferences on population history and evolution. All applications would greatly benefit from reliable locus-specific mutation rates, to improve forensic probability calculations and interpretations of diversity data. However, estimates of mutation rate from father-son transmissions are available for few loci and have large confidence intervals, because of the small number of m ...[more]

PMID: 20823913

Similar Datasets

Project description:A total of 2 548 unrelated healthy father-son pairs from a Northern Han Chinese population were genotyped at 41 Y chromosomal short tandem repeat (Y-STRs) including DYS19, DYS388, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS444, DYS447, DYS448, DYS449, DYS456, DYS458, DYS460, DYS481, DYS518, DYS522, DYS549, DYS533, DYS557, DYS570, DYS576, DYS593, DYS596, DYS627, DYS635, DYS643, DYS645, Y-GATA-H4, DYF387S1a/b, DYF404S1a/b, DYS385a/b, and DYS527a/b. In 2 548 father samples, 2 387 unique haplotypes were detected with the haplotype diversity and discrimination capacity values of 0.999 956 608 and 0.96 741 007. The average gene diversity (GD) value was 0.6934 with a range from 0.1051 at DYS645 to 0.9657 at DYS385a/b. When comparing alleles at 24 overlapped Y-STRs between the ForenSeq™ deoxyribonucleic acid (DNA) Signature Prep Kit on the MiSeq FGx® Forensic Genomics System and the Goldeneye® DNA ID Y Plus Kit on the Applied Biosystems™ 3730 DNA Analyzer from 308 father samples in mutational pairs, 258 alleles were detected by massively parallel sequencing (MPS) typing including 156 length-based alleles that could be obtained by capillary electrophoresis (CE) typing, 95 repeat region (RR) variant alleles and seven flanking region variant alleles. Hereof, we found 16 novel RR variant alleles and firstly identified two SNPs (rs2016239814 at DYS19 and rs2089968964 at DYS448) and one 4-bp deletion (rs2053269960 at DYS439) that had been validated by the Database of Short Genetic Variation. Sanger sequencing or MPS was employed to confirm 356 mutations from 104 468 allele transfers generated from CE, where 96.63% resulted in one-step mutations, 2.25% in two-step, and 1.12% in multi-step, and the overall ratio of repeat gains versus losses was balanced (173 gains vs. 183 losses). In 308 father-son pairs, 268 pairs occurred mutations at a single locus, 33 pairs at two loci, six pairs at three loci, and one pair at four loci. The average Y-STR mutation rate at 41 Y-STRs was ⁓3.4 × 10-3 (95% confidence intervals: 3.1 × 10-3-3.8 × 10-3). The mutation rates at DYS576 and DYS627 were higher than 1 × 10-2 in Northern Han Chinese, whilst the mutation rates at DYF387S1a/b, DYF404S1a/b, DYS449, DYS518, and DYS570 were lower than initially defined. In this study, the classical molecular factors (the longer STR region, the more complex motif and the order father) were confirmed to drive Y-STR mutation rates increased, but the length of repeat unit did not conform to the convention. Lastly, the interactive graphical and installable StatsY was developed to facilitate forensic scientists to automatically calculate allele and haplotype frequencies, forensic parameters, and mutation rates at Y-STRs.Key points308 of 2 548 father-son pairs from Northern Han Chinese occurred at least one mutation(s) across 41 Y-STRs.Sanger sequencing or MPS was employed to confirm those mutations generated from CE.The longer STR region, the more complex motif and the order father drove Y-STR mutation rates increased.StatsY was developed to calculate allele and haplotype frequencies, forensic parameters and mutation rates at Y-STRs.

Project description:Rapidly mutating Y-STRs (RM Y-STRs) harbor great potential to distinguish male relatives and achieve male identification. However, forensic applications were greatly limited by the small number of the initially identified 14 RM Y-STRs. Recently, with the emergence of 12 novel RM Y-STRs, an integrated panel named RMplex was introduced, which contains all 26 RM Y-STRs and four fast mutating Y-STRs (FM Y-STRs). To obtain the first data on the mutation rates and father-son differentiation rates of the 30 newly proposed Y-STRs in Chinese populations, we performed an empirical mutation study on 307 DNA-confirmed Chinese paternal pairs. Previously reported mutation rates for 14 RM Y-STRs in Chinese and European populations were pooled and merged with our data. The highest meiosis number for the two groups reached 4771 and 2687, respectively. Five loci showed significant differences between the populations (DYS570, DYS399S1, DYS547, DYS612, and DYF403S1b). For the new panel covering 30 Y-STR loci, our results show extensive differences in the mutation rates between the two populations, as well. 10 RM Y-STR loci showed relatively low mutation rates (10-3-10-2 per meiosis) and 2 FM Y-STR loci had rapid mutation rates (> 10-2 per meiosis) in the Chinese population. Several-fold differences in mutation rates were found in nine Y-STR loci between the Chinese and reference populations, with two loci having significantly higher mutation rates and one locus with a significantly lower mutation rate in the Chinese population (P < 0.05). Eighteen RM Y-STRs (> 10-2 per meiosis), 8 FM Y-STR loci (5×10-3-10-2 per meiosis), 3 moderately mutating Y-STRs (MM Y-STRs, 10-3-5×10-3 per meiosis), and one locus with no observed mutation events were identified in the Chinese population. 40.06% of the Chinese paternity pairs were discriminated with RMplex while only 20.84% with the initial 14 RM Y-STRs, indicating that RMplex is beneficial for distinguishing paternally related males. Future studies on populations of different genetic backgrounds are necessary to obtain comprehensive estimates of mutation rates at these new loci.

Dataset Information

Mutation rate estimates for 110 Y-chromosome STRs combining population and father-son pair data.

Publications

Mutation rate estimates for 110 Y-chromosome STRs combining population and father-son pair data.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets