Haplogroup-specific deviation from the stepwise mutation model at the microsatellite loci DYS388 and DYS392

Deviation from the stepwise mutation model (SMM) at specific human microsat ellite loci has implications for population genetic and forensic investigat ions. In the present study, data on six Y chromosome-specific microsatellit es were pooled for 455 paternally unrelated males from six Middle Eastern p opulations. All chromosomes were assigned to three haplogroups defined by s ix binary polymorphisms. Two of the microsatellite loci tested, DYS388 and DYS392, displayed marked haplogroup-specific differences in their allele va riability. A bimodal distribution of short and long alleles was observed fo r DYS388 in haplogroup 1 and for DYS392 in haplogroups 1 and 2. Further inv estigation showed that the short/long alleles segregated almost completely between genealogically distinct haplogroups defined by additional binary ma rkers. Thus, these two loci have a discriminatory power similar to a binary polymorphism. DYS388 was characterised by an extremely low mutation rate i n haplogroups 2 and 3, as was DYS392 in haplogroup 3. Sequence analysis of the repeat regions at the two loci revealed no irregularities, Indicating t hat the triplet expansion in these loci is not controlled by sequence varia tion at the repeat level. A high frequency of long DYS388 alleles has, so f ar, been found only in populations originating in the Middle East, suggesti ng that this microsatellite is useful as a region-specific marker.