REFINED MAPPING OF THE USHER-SYNDROME TYPE-III LOCUS ON CHROMOSOME-3,EXCLUSION OF CANDIDATE GENES, AND IDENTIFICATION OF THE PUTATIVE MOUSE HOMOLOGOUS REGION

A locus for Usher syndrome type III (USH3; MIM No. 276902) was recentl y assigned to a 5-cM region on chromosome 3q. We constructed a yeast a rtificial chromosome contig that allowed us to position novel polymorp hisms in the region. These were typed in a total of 32 pedigrees from a geographically isolated Finnish founder population in which a putati ve single ancestral USH3 mutation segregates. A multipoint linkage ana lysis assigned USH3 to a 4-cM region between D3S1555 and a novel marke r D3S3625. By analysis of linkage disequilibrium and historical recomb inations in 77 USH3 chromosomes, the location of the Finnish USH3 muta tion could be narrowed to an approximately 1-cM interval between the m arkers 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. (C) 1996 Acad emic Press, Inc.