Refined mapping of the Usher syndrome type III locus on chromosome 3, exclusion of candidate genes, and identification of the putative mouse homologous region

Abstract

A locus for Usher syndrome type III (USH3; MIM No. 276902) was recently assigned to a 5-cM region on chromosome 3q. We constructed a yeast artificial chromosome contig that allowed us to position novel polymorphisms in the region. These were typed in a total of 32 pedigrees from a geographically isolated Finnish founder population in which a putative single ancestral USH3 mutation segregates. A multipoint linkage analysis assigned USH3 to a 4-cM region between D3S1555 and a novel marker D3S3625. By analysis of linkage disequilibrium and historical recombinations in 77 USH3 chromosomes, the location of the Finnish USH3 mutation could be narrowed to an approximately 1-cM interval between the markers D3S1299 and D3S3625. A gene for profilin-2 (PFN2) was mapped in the vicinity and excluded as a candidate for USH3 by sequencing. The putative mouse homolog of PFN2 was mapped to mouse chromosome 3, thus suggesting a localization for the mouse homolog of USH3.