The Usher syndromes (USH) are autosomal recessive diseases characterized by sensorineural hearing impairment and progressive visual deterioration. Clinical differences in vestibular function can be demonstrated in affected persons, and as a result, two subtypes are recognized. Persons with Usher syndrome type I (USH1) have vestibular dysfunction and persons with Usher syndrome type II (USH2) do not. Two loci for USHI recently have been localized on chromosome 11. This proposal will: 1) Establish whether specific clinical differences exist in these two sub- populations of USH1. This will be determined by studying olfactory acuity, morphology of the nasal cilia, and serum docosahexaenoate, arachidonate and sarcosine levels. Prior studies suggest that differences may exist, but tests have not been conducted on homogeneous USH1 populations. 2) Refine the genetic and physical lap of chromosome 11 in the region of the USH1 locus on 11p. Short tandem repeat polymorphisms will be identified and mapped relative to markers on the existing map of chromosome 11p and the USH1 gene. Using standard linkage techniques, the USH1 gene will be localized to a specific subchromosomal region. 3) Use exon trapping to identify potential transcripts in the region of the USH1 gene. The ultimate objective of this research grant is to clone and sequence the USH1 genes on chromosome 11. This will provide a better understanding of the pathologic processes involved in USH and may have important implications on remediation and/or prevention of this disease.
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