This application describes a proposed study of X-linked and autosomal recessive types of retinitis pigmentosa utilizing recombiant DNA technology. Leucocyte DNA will be isolated from members of ascertained families with inherited ocular degenerative diseases. The kindreds showing segregation of the gene for X-linked retinitis pigmentosa will be analyzed with a number of cloned DNA probes which detect restriction fragment length polymorphisms at specific X-chromosome loci. Special consideration will be given to probe L1.28 from Xp11.3 and other nearby probes. The goal will be to develop additional polymorphic markers closely linked to the X-linked retinitis pigmentosa locus and flanking that locus. The final set of probes will make genetic counseling based on linkage more accurate and available to a larger number of families. In addition, affected males from 30 to 50 different X-linked pedigrees will be tested for X-chromosome deletion of the L1.28 locus and other nearby probe loci. Both aspects of the work on X-linked retinitis pigmentosa should ultimately set the stage for a later isolation of the disease locus itself. Lastly, kindreds with large sib-ships affected with various types of autosomal recessive retinitis pigmentosa will be ascertained and will form the basis of a search for the chromosomal locus of at least one form of this disease. Special attention will be paid to kindreds affected with the Bardet-Biedl syndrome, since four large kindreds with this syndrome have already been identified. Autosomal DNA probes detecting restriction fragment polymorphisms will be used in this analysis. A polymorphism panel will be constructed to increase the number of probes which detect loci with 4 or more alleles. The applicants estimate a high probability of successful chromosome localization of at least one type of autosomal recessive retinitis pigmentosa. Such successful gene localization will allow greatly improved genetic counseling in this disease, as well as allow further studies into the nature of its genetic heterogeneity.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Mammalian Genetics Study Section (MGN)
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Harvard University
Schools of Medicine
United States
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Ringens, P J; Fang, M; Shinohara, T et al. (1990) Analysis of genes coding for S-antigen, interstitial retinol binding protein, and the alpha-subunit of cone transducin in patients with retinitis pigmentosa. Invest Ophthalmol Vis Sci 31:1421-6
Mukai, S; Dryja, T P; Bruns, G A et al. (1985) Linkage between the X-linked retinitis pigmentosa locus and the L1.28 locus. Am J Ophthalmol 100:225-9