An extensive analysis of Y-chromosomal microsatellite haplotypes in globally dispersed human populations.

The genetic variance at seven Y-chromosomal microsatellite loci (or short tandem repeats [STRs]) was studied among 986 male individuals from 20 globally dispersed human populations. A total of 598 different haplotypes were observed, of which 437 (73.1%) were each found in a single male only. Population-specific haplotype-diversity values were.86-.99. Analyses of haplotype diversity and population-specific haplotypes revealed marked population-structure differences between more-isolated indigenous populations (e.g., Central African Pygmies or Greenland Inuit) and more-admixed populations (e.g., Europeans or Surinamese). Furthermore, male individuals from isolated indigenous populations shared haplotypes mainly with male individuals from their own population. By analysis of molecular variance, we found that 76.8% of the total genetic variance present among these male individuals could be attributed to genetic differences between male individuals who were members of the same population. Haplotype sharing between populations, phi(ST) statistics, and phylogenetic analysis identified close genetic affinities among European populations and among New Guinean populations. Our data illustrate that Y-chromosomal STR haplotypes are an ideal tool for the study of the genetic affinities between groups of male subjects and for detection of population structure.

Y-chromosome-specific microsatellite mutation rates re-examined using a minisatellite, MSY1.

Polymorphic Y-chromosome-specific microsatellites are becoming increasingly used in evolutionary and forensic studies and, in particular, in dating the origins of Y-chromosomal lineages. Previously, haplotyping of Y chromosomes from males belonging to a set of deep-rooting pedigrees was used to estimate a conservative average Y-chromosomal microsatellite mutation rate of 2.1 x 10(-3)per locus per generation. A number of males showed multiple differences in haplotypes compared with other males within their pedigrees, and these were excluded from the calculation of this estimate, on the grounds that non-paternity was a more probable explanation than multiple mutation within a lineage. Here we reanalyse the pedigrees using an independent highly polymorphic system, the Y-specific minisatellite, MSY1. This supports the hypothesis of non-paternity where more than one microsatellite difference was observed, provides further support for the previously deduced microsatellite mutation rate and throws light on the mutation dynamics of MSY1 itself, suggesting that single-step changes are not the only mode of mutation.

Applications of microsatellite-based Y chromosome haplotyping.

Y-chromosomal microsatellites have been investigated for the purposes of application to male identification, population genetics and population history. With nine markers, every male in a German population sample (n = 70) could be identified by an individual-specific Y microsatellite haplotype. The analysis of 474 unrelated males of nine human populations with seven markers revealed 301 different Y haplotypes. The analysis of molecular variance (AMOVA) approach was used to detect male population characteristics of Y microsatellite haplotypes. With pairwise comparisons of inter-population variance, most of the populations could be distinguished significantly. Sixty individuals from different male populations in Asia and Northern Europe carrying a novel Y-chromosomal T-->C transition show reduced microsatellite variability together with haplotype similarities. Microsatellite data suggest that the mutation occurred recently in Asia, supporting the hypothesis of Asian ancestry of some northern European populations.

Estimating Y chromosome specific microsatellite mutation frequencies using deep rooting pedigrees.

Recently, a set of highly polymorphic chromosome Y specific microsatellites became available for forensic, population genetic and evolutionary studies. However, the lack of a mutation frequency estimate for these loci prevents a reliable application. We therefore used seven chromosome Y tetranucleotide repeat loci to screen 42 males who are descendants from 12 'founding fathers' by a total number of 213 generations. As a result, we were able to estimate an average chromosome Y tetranucleotide mutation frequency of 0.20% (95% CIL 0.05-0.55). This closely matches the often cited Weber and Wong estimate of 0.21% for a set of autosomal tetranucleotide repeats. Expanding the set of microsatellites with two more loci (a tri- and a penta-nucleotide repeat locus) an average chromosome Y microsatellite mutation frequency of 0.21% (95% CIL 0.06-0.49) was found. These estimates suggest that microsatellites on the Y chromosome have mutation frequencies comparable to those on the autosomes. This supports the hypothesis that slippage-generated growth is the driving force behind the microsatellite variability.

Analysis of molecular variance (AMOVA) of Y-chromosome-specific microsatellites in two closely related human populations.

The analysis of seven Y-chromosome-specific microsatellite loci revealed a high level of polymorphism in two closely related human populations (Dutch, n = 89, and German, n = 70). Four of these loci were found to generate at least 77 different haplotypes, only 15 of which were shared by the two populations. These results demonstrate that highly informative PCR-based DNA typing of the Y chromosome is now feasible. Assuming a stepwise mutation model, a network comprising all minimum spanning evolutionary trees connecting the haplotypes was constructed. Analysis of molecular variance based upon this network indicated that the within-population heterogeneity with respect to haplotype descent was significantly smaller than the between-population heterogeneity, suggesting that males were more closely related to males from their own population as opposed to males from the other population. These findings suggest that Y-chromosomal microsatellites might be very useful not only for forensic purposes but also in association studies of multifactorial traits, allowing the characterization of the level of genetic distinctiveness of supposedly inbred or isolated populations and discrimination even between closely related populations.