DYNAMIC MUTATION LOCI - ALLELE DISTRIBUTIONS IN DIFFERENT POPULATIONS

To assess the relative contributions of trans-acting factors (replicat ion and repair functions) and cis-acting elements (repeat and flanking DNA composition) to the mechanism of trinucleotide repeat sequence mu tation we have analysed the distribution of copy number polymorphisms at 12 loci associated with dynamic mutations in 15 populations of diff erent ethnic origins. Genome wide instability of repeats in a particul ar population would be evidence of trans-acting factor instigation of the mutation process, whereas instability at a particular locus (perha ps even in several populations) would be evidence that the composition of the particular locus was the most significant factor contributing to mutation. The FRA16A locus is highly polymorphic in only the Europe an population. Some other loci exhibit distinct distributions of allel es between different populations. Therefore sequences in the vicinity of the repeat-the cis component of a particular locus-appear(s) to be more important in the mutation mechanism than sporadic genome-wide ins tability induced by trans-acting factors such as the DNA mismatch repa ir enzymes.