FUNCTIONAL GENOMICS OF A DEAFNESS/BLINDNESS SYNDROME

基因负责Usher综合征1C型，常染色体

DESCRIPTION: The gene responsible for Usher Syndrome Type 1C, an autosomal recessively inherited deafness/blindness syndrome, was previously mapped by genetic linkage analysis between the markers D11S861 and 899. The major focus of this proposal is to clone, and characterize the USH1C gene and its product, providing critical information on the underlying pathophysiological mechanism for this and other forms of dual neurosensory syndromes. Since this region was found to be refractory to cloning using YAC (yeast artificial chromosome) based vectors, a P1-artificial -chromosome (PAC) contig was constructed. The 400 kb contig encompassing the critical region is providing the genomic resources for a gene hunt using exon trapping, cDNA selection, and direct sequencing. We are currently investigating several new transcription units which we have identified and mapped into the critical region. The current proposal is directed at (1) identifying transcription units in the critical region; (2) analyzing cDNAs to determine which represent intriguing candidate genes; (3) examining patient DNA for mutations by sequencing to identify the gene, and; (4) characterizing the gene and its product at the tissue and cellular levels. Since the phenotype for Usher type 1C is indistinguishable with the other five USH1 loci, this study may yield insights into the mechanism responsible for profound deafness, vestibular dysfunction and progressive retinal degeneration and provide new insights into the syndrome responsible for the majority of children born with dual neurosensory degeneration.