MUTATIONAL PROCESSES OF SIMPLE-SEQUENCE REPEAT LOCI IN HUMAN-POPULATIONS

Mutational processes of simple sequence repeats (SSRs) in complex geno mes are poorly understood. We examined these processes by introducing a two-phase mutation model. In this model, most mutations are single-s tep changes, but infrequent large jumps in repeat number also occur. W e used computer simulations to determine expected values of statistics that reflect frequency distributions of allele size for the two-phase model and two alternatives, the one-step and geometric models. The th eoretical expectations for each model were tested by comparison with o bserved values for 10 SSR loci genotyped in the Sardinian population, whose genetic and demographic histories have been previously reconstru cted. The two-phase model provided the best fit to the data for most o f these loci in this population. In the analysis we assumed that the l oci were neutral and that this population had undergone rapid populati on growth. Recent observations made for unstable trinucleotide repeats support our suggestion that frequent small changes and rare large cha nges in repeat number represent two distinct classes of mutation at SS R loci. We genotyped the same 10 loci in Egyptian and sub-Saharan Afri can samples to assess the utility of SSRs for studying the divergence of populations and found that estimates of interpopulation distances f rom SSRs were similar to those derived from analysis of mitochondrial DNA.