A Comprehensive Survey of Human Y-Chromosomal Microsatellites

Abstract

We have screened the nearly complete DNA sequence of the human Y chromosome for microsatellites (short tandem repeats) that meet the criteria of having a repeat-unit size of > or = 3 and a repeat count of > or = 8 and thus are likely to be easy to genotype accurately and to be polymorphic. Candidate loci were tested in silico for novelty and for probable Y specificity, and then they were tested experimentally to identify Y-specific loci and to assess their polymorphism. This yielded 166 useful new Y-chromosomal microsatellites, 139 of which were polymorphic, in a sample of eight diverse Y chromosomes representing eight Y-SNP haplogroups. This large sample of microsatellites, together with 28 previously known markers analyzed here--all sharing a common evolutionary history--allowed us to investigate the factors influencing their variation. For simple microsatellites, the average repeat count accounted for the highest proportion of repeat variance (approximately 34%). For complex microsatellites, the largest proportion of the variance (again, approximately 34%) was explained by the average repeat count of the longest homogeneous array, which normally is variable. In these complex microsatellites, the additional repeats outside the longest homogeneous array significantly increased the variance, but this was lower than the variance of a simple microsatellite with the same total repeat count. As a result of this work, a large number of new, highly polymorphic Y-chromosomal microsatellites are now available for population-genetic, evolutionary, genealogical, and forensic investigations.

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

“…19 Thus, in addition to R V and R H , mean allele repeat count (A: estimated from the population data), CG content in motif (P CG : proportion of CG base pairs in the motif), and the categorical variables motif size (M: tri-, tetra-, penta-or hexanucleotide motif) and repeat structure (S: simple versus complex) were considered explanatory variables. Information about Y-STR motifs was obtained from Kayser et al, Järve et al, Gusmão et al and Leat et al [21][22][23][24] Problems of multicollinearity were evaluated on the full model (containing all explanatory variables), as collinear variables represent partial redundant information and correlations between variables generate unreliable individual estimates of regression coefficients. Alternative models obtained after removing different combinations of collinear variables were considered and reduced by stepwise removal of variables to minimize Akaike information criterion (AIC, ie, a standard procedure to find the explanatory variable combination, which accounts for the maximum of the variability with the minimum number of variables).…”

“…Regarding trinucleotide markers, Kayser et al 21 found that these had often lower variance than tetranucleotide markers, probably because of the effect of low absolute repeat allele lengths included in their sample. 21 Lower mutability of shorter alleles compared with longer ones has been observed several times. 32,33,12,34 Accordingly, our results show that the variation in meiosis mutation rates could be significantly explained by mean repeat count (Supplementary Tables S5 and S6).…”

“…38,32,22 These results might be due to the lack of effect of repeat structure. However, our qualitative classification of loci as 'simple' or 'complex' could be missing essential information of complex loci (ie, differential length of the homogeneous array or combination of variable and constant repeats 21 ) affecting the mutation rate. More precise definitions of the degree of complexity, similar to those used in Kayser et al, 21 could yield different results, but require detailed information on loci not readily available.…”

Microsatellite Length Differences Between Humans and Chimpanzees at Autosomal Loci Are Not Found at Equivalent Haploid Y Chromosomal Loci

“…For example, although most mutations involve the gain or loss of a single repeat unit, some studies report a tendency for gains in length to outnumber losses Kayser et al 2000;Dupuy et al 2004), while others report either unbiased mutations (Brinkmann et al 1998;Xu et al 2000) or a tendency to decline in length (Sajantila et al 1999) especially among very long microsatellites (Xu et al 2000;Huang et al 2002). Mutation rates and other properties appear to depend critically on the structure of the microsatellite, with repeat number and the degree of interruption both being important (Brinkmann et al 1998;Kayser et al 2000Kayser et al , 2004Huang et al 2002). Such structural variation may help to explain the contradictory nature of some of these studies (for overview see Ellegren 2004).…”

“…During marker development, highly polymorphic loci are normally preferred and, since the degree of polymorphism and microsatellite length are positively correlated (e.g., Kayser et al 2004), this usually means that loci are chosen to be as long as possible in the target species. As a consequence, there is a tendency for markers to be longer and thus more polymorphic in the species from which they were originally cloned, relative to homologous products in related species they are applied to.…”