Characteristics and Frequency of Germline Mutations at Microsatellite Loci from the Human Y Chromosome, as Revealed by Direct Observation in Father/Son Pairs

Abstract

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.

Drawing the history of the Hutterite population on a genetic landscape: inference from Y-chromosome and mtDNA genotypes

“…Median-joining networks were constructed by use of the Network 4.1 program 35,36 (http://www.fluxus-engineering.com), based on Y-chromosomal haplotype data and on nucleotide variation in the HVRI region (positions from 16048 to 16383) and in the coding region of the mtDNA. The repeat sizes of the Y-chromosomal microsatellite markers were weighted according to the mutation rates of the different loci 37 and the e value was set to 0. HVRI-nucleotide positions were weighted according to Roostalu et al 38 and an e value of 0 was used.…”

“…By direct count in deep-rooted pedigrees, a mutation rate of 2Â10 À3 per generation has been estimated, 40 and by studying father/son pairs, a similar average mutation rate of 3.17Â10 À3 per locus per generation was estimated. 37 A recent study analyzed 17 microsatellite markers for 18 earlier published studies in combination with a new dataset of father/son pairs (135 212 meiotic transfers in total) and found a median mutation rate of 2.2Â10 À3 . 41 Phylogeny-based studies such as Zhivotovsky et al 42 and Forster et al 43 estimated a lower mutation rate of 6.9Â10 À4 per locus per 25 years and 2.6Â10 À4 per 20 years, respectively.…”

Haplotypic relationship between SNP and microsatellite markers at the NOS2A locus in two populations

“…55 Recombination may also have contributed to NOS2A À2.6 microsatellite mutation, but data from other repeat elements suggest that this mechanism is unusual in microsatellite evolution. 56 The relationship between repeat motif size and microsatellite mutation rate is unclear. Indirect analysis Figure 3 Repeat elements in the proximal NOS2A promoter.…”

Correlation Between the Allelic Distribution of STRs in a Finnish Population and Phenotypically Different Gastrointestinal Tumours: A Study Using Four X‐Chromosomal Markers (DXS7423, DXS8377, ARA, DXS101)

“…Normally, when the generation of errors and their repair are in balance, the mutation frequency at STRs has been estimated to be roughly one mutation per one thousand cell divisions (Weber & Wong, 1993). Family studies of STR markers have revealed a germline mutation rate from 10 − 4 to 10 − 2 , correlating with structural parameters such as the number and complexity of the repeats (Brinkmann et al 1998a(Brinkmann et al , 1998bSajantila et al 1999;Kayser et al 2000;Kayser & Sajantila 2001;Leopoldino & Pena 2003).…”