RELATIVE MUTATION-RATES AT DINUCLEOTIDE, TRINUCLEOTIDE, AND TETRANUCLEOTIDE MICROSATELLITE LOCI

Using the generalized stepwise mutation model, we propose a method of estimating the relative mutation rates of microsatellite loci, grouped by the repeat motif, Applying ANOVA to the distributions of the allel e sizes at microsatellite loci from a set of populations, grouped by r epeat motif types, we estimated the effect of population size differen ces and mutation rate differences among loci, This provides an estimat e of motif-type-specific mutation rates up to a multiplicative constan t, Applications to four different sets of di-, tri-, and tetranucleoti de loci from a number of human populations reveal that, on average, th e non-disease-causing microsatellite loci have mutation rates inversel y related to their motif sizes, The dinucleotides appear to have mutat ion rates 1.5-2 times higher than the tetranucleotides, and the non-di sease-causing trinucleotides have mutation rates intermediate between the di- and tetranucleotides. In contrast, the disease-causing trinucl eotides have mutation rates 3.9-6.9 times larger than the tetranucleot ides, Comparison of these estimates with the direct observations of mu tation rates at microsatellites indicates that the earlier suggestion of higher mutation rates of tetranucleotides in comparison with the di nucleotides may stem from a nonrandom sampling of tetranucleotide loci in direct mutation assays.