A sequence-ready map of the Usher syndrome type III critical region on chromosome 3q

Usher syndrome type 3 (USH3; MIM 276902) is an autosomal recessive disorder associated with progressive hearing loss and retinal degeneration. We rece ntly refined the localization of USH3 to a 1-cM genetic interval between ma rkers D3S1299 and D3S3625. We have now constructed a bacterial artificial c hromosome contig over the region. Novel polymorphic markers were generated and physically fine-mapped, allowing further narrowing of the critical inte rval to a 250-kb genomic fragment. Of seven ESTs mapping to the initial cri tical region, WI-11588 and SHGC-133 represent the human SIAH2 gene, which w as excluded as a candidate for USH3 by sequencing and subsequently, by its position. KIAA0001 and D3S3882 derive from the transcript of a putative G-p rotein-coupled receptor gene that was excluded as a candidate by sequencing of patient DNA. These data provide a basis for the sequencing and final ch aracterization of the USH3 region and isolation of the disease gene. (C) 20 00 Academic Press.