Genes coding for inherited eye disorders have been mapped by family studies and genetic linkage tests to two specific regions (11 q13 and 11p14/15.1) on human chromosome 11.
The aim of this proposal is to locate and clone these genes associated with impaired sight. This will be accomplished by generating an ordered overlapping clone map consisting of chromosome ii specific YAC (yeast artificial chromosome) clones across the regions identified by linkage analysis to harbor the disease genes. CA repeats will be developed from YAC clones at 1 Mb intervals and used to identify by linkage analysis those YAC clones flanking the disease loci. cDNA selection and exon trapping will be applied to directly identify coding regions from those genomic clones identified in the smallest region harboring the genes. Resulting cDNA clones will be sequenced to test for criteria of coding regions. Candidate cDNA and corresponding genomic clones will be used to examine affected patients for mutations by single strand conformational polymorphisms (SSCP) and denaturing gradient gel electrophoresis (DOGE). The molecular and genetic abnormality for each disorder will be described by cloning and characterizing the genes responsible for these sight disorders. Eventual sequencing of the genes will allow a determination of the protein structure coded by the gene and its physiologic function. This knowledge will allow new insights into several common sight disorders.
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