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

The Y-chromosomal short tandem repeat (Y-STR) polymorphisms included in the AmpFlSTR® Yfiler® polymerase chain reaction amplification kit have become widely used for forensic and evolutionary applications where a reliable knowledge on mutation properties is necessary for correct data interpretation. Therefore, we investigated the 17 Yfiler Y-STRs in 1,730–1,764 DNA-confirmed father–son pairs per locus and found 84 sequence-confirmed mutations among the 29,792 meiotic transfers covered. Of the 84 mutations, 83 (98.8%) were single-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). Medians from Bayesian estimation of locus-specific mutation rates ranged from 0.0003 for DYS448 to 0.0074 for DYS458, with a median rate across all 17 Y-STRs of 0.0025. The mean age (at the time of son’s birth) of fathers with mutations was with 34.40 (±11.63) years higher than that of fathers without ones at 30.32 (±10.22) years, a difference that is highly statistically significant (p < 0.001). A Poisson-based modeling revealed that the Y-STR mutation rate increased with increasing father’s age on a statistically significant level (α = 0.0294, 2.5% quantile = 0.0001). From combining our data with those previously published, considering all together 135,212 meiotic events and 331 mutations, we conclude for the Yfiler Y-STRs that (1) none had a mutation rate of >1%, 12 had mutation rates of >0.1% and four of <0.1%, (2) single-repeat changes were strongly favored 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 two mutations each) has consequences for determining the threshold of allelic differences to conclude exclusion constellations in future applications of Y-STRs in paternity testing and pedigree analyses

HERC1 polymorphisms: population-specific variations in haplotype composition

Human HERC1 is one of six HERC proteins and may play an important role in intracellular membrane trafficking. The human HERC1 gene is suggested to have been affected by local positive selection. To assess the global frequency distributions of coding and non-coding single nucleotide polymorphisms (SNPs) in the HERC1 gene, we developed a new simultaneous genotyping method for four SNPs, and applied this method to investigate 1213 individuals from 12 global populations. The results confirmed remarked differences in the allele and haplotype frequencies between East Asian and non-East Asian populations. One of the three common haplotypes observed was found to be characteristic of East Asians, who showed a relatively uniform distribution of haplotypes. Information on haplotypes would be useful for testing the function of polymorphisms in the HERC1 gene. This is the first study to investigate the distribution of HERC1 polymorphisms in various populations.Human HERC1 is one of six HERC proteins and may play an important role in intracellular membrane trafficking. The human HERC1 gene is suggested to have been affected by local positive selection. To assess the global frequency distributions of coding and non-coding single nucleotide polymorphisms (SNPs) in the HERC1 gene, we developed a new simultaneous genotyping method for four SNPs, and applied this method to investigate 1213 individuals from 12 global populations. The results confirmed remarked differences in the allele and haplotype frequencies between East Asian and non-East Asian populations. One of the three common haplotypes observed was found to be characteristic of East Asians, who showed a relatively uniform distribution of haplotypes. Information on haplotypes would be useful for testing the function of polymorphisms in the HERC1 gene. This is the first study to investigate the distribution of HERC1 polymorphisms in various populations. Copyright (C) 2009 John Wiley & Sons, Ltd

A Japanese-specific allele in the GALNT11 gene

In this study, five single nucleotide polymorphisms (SNPs) in the ABCC4, FBN1, CEP152, ZNF804B, and GALNT11 genes were investigated to assess allele frequencies in 14 different populations by a novel pentaplex PCR method. All SNPs were polymorphic in East Asians, whereas mutant alleles were absent or rare in non-East Asians. The frequencies of a mutant allele in FBN1 (rs140598) showed a north-south downward cline in East Asia, whereas those of a mutant allele in ZNF804B (rs1916830) were relatively uniform in East Asia. The highest frequencies of mutant alleles in ABCC4 (rs3765534), CEP152 (rs2289178), and GALNT11 (rs3778922) were observed in Okinawa. The mutant allele in GALNT11 was found only in Far-East Asian populations: the frequencies were about 0.153 in Okinawa, 0.076 in the main island of Japan, and 0.017-0.004 in Korea. These five East Asian- and Japanese-specific SNPs would be useful markers for forensic individualization, in particular, as ancestry-informative markers. (C) 2010 Elsevier Ireland Ltd. All rights reserved

Characteristics and frequency of germline mutations at microsatellite loci from the human Y chromosome revealed by direct observation in father/son pairs

A number of applications of analysis of human Y-chromosome microsatellite loci to human evolution and forensic science require reliable estimates of the mutation rate and knowledge of the mutational mechanism. We therefore screened a total of 4,999 meioses from father/son pairs with confirmed paternity (probability >/=99. 9%) at 15 Y-chromosomal microsatellite loci and identified 14 mutations. The locus-specific mutation-rate estimates were 0-8. 58x10-3, and the average mutation rate estimates were 3.17x10-3 (95% confidence interval [CI] 1.89-4.94x10-3) across 8 tetranucleotide microsatellites and 2.80x10-3 (95% CI 1.72-4.27x10-3) across all 15 Y-chromosomal microsatellites studied. Our data show a mutational bias toward length increase, on the basis of observation of more repeat gains than losses (10:4). The data are in almost complete agreement with the stepwise-mutation model, with 13 single-repeat changes and 1 double-repeat change. Sequence analysis revealed that all mutations occurred in uninterrupted homogenous arrays of >/=11 repeats. We conclude that mutation rates and characteristics of human Y-chromosomal microsatellites are consistent with those of autosomal microsatellites. This indicates that the general mutational mechanism of microsatellites is independent of recombination

A Comprehensive Analysis of Recently Integrated Human Ta L1 Elements

The Ta (transcribed, subset a) subfamily of L1 LINEs (long interspersed elements) is characterized by a 3-bp ACA sequence in the 3′ untranslated region and contains ∼520 members in the human genome. Here, we have extracted 468 Ta L1Hs (L1 human specific) elements from the draft human genomic sequence and screened individual elements using polymerase-chain-reaction (PCR) assays to determine their phylogenetic origin and levels of human genomic diversity. One hundred twenty-four of the elements amenable to complete sequence analysis were full length (∼6 kb) and have apparently escaped any 5′ truncation. Forty-four of these full-length elements have two intact open reading frames and may be capable of retrotransposition. Sequence analysis of the Ta L1 elements showed a low level of nucleotide divergence with an estimated age of 1.99 million years, suggesting that expansion of the L1 Ta subfamily occurred after the divergence of humans and African apes. A total of 262 Ta L1 elements were screened with PCR-based assays to determine their phylogenetic origin and the level of human genomic variation associated with each element. All of the Ta L1 elements analyzed by PCR were absent from the orthologous positions in nonhuman primate genomes, except for a single element (L1HS72) that was also present in the common (Pan troglodytes) and pygmy (P. paniscus) chimpanzee genomes. Sequence analysis revealed that this single exception is the product of a gene conversion event involving an older preexisting L1 element. One hundred fifteen (45%) of the Ta L1 elements were polymorphic with respect to insertion presence or absence and will serve as identical-by-descent markers for the study of human evolution