A polymorphic X-linked tetranucleotide repeat locus displaying a high rate of new mutation: implications for mechanisms of mutation at short tandem repeat loci.

We report a high rate of new mutation at a short tandem repeat sequence polymorphism (STR, microsatellite) at locus DXS981 on the proximal long arm of the human X chromosome. Among individuals of the CEPH pedigrees, new allele lengths are detected at this tetranucleotide repeat with a frequency of approximately 1.5%. In cases where the origin of the new allele was traceable, new mutant alleles at DXS981 varied by exactly one repeat length (4 bp) relative to that on the originating parental chromosome. Complete linkage disequilibrium between two additional insertion/deletion polymorphisms which closely flank the variation at the tetranucleotide repeat suggests that, to the extent that these new mutants are germline in origin, they are not generated by unequal exchange between homologues. Considered in light of the types of new mutations detected and the substantial linkage disequilibrium at this locus, these data have implications for the mechanism of variation at other loci containing short tandemly repeated sequences.