| Summary: | Thesis (Ph.D.)--Memorial University of Newfoundland, 2000. Medicine Includes bibliographical references Bardet-Biedi syndrome (BBS) is a rare autosomal recessive disorder characterized by congenital dysmorphic extremities, infantile onset obesity, progressive retinal degeneration, renal abnormalities, and male hypogonadism. There are at least five genetic loci, four previously mapped (3p, 1 lq, 15q and 16q), that give the same pleiotropic BBS phenotype. The limited number of cases and the genetic heterogeneity of BBS have hindered efforts to positionally clone the BBS genes. Newfoundland, a genetic isolate, is enriched for BBS with a prevalence (1/17,500) that is ten times higher than the world estimate. The availability of DNA from 17 of the 22 identified BBS families provided an opportunity to study the molecular genetics of BBS in Newfoundland. -- Seventeen families were genotyped and linkage and haplotype analyses were conducted at each of the four mapped loci (BBSI-BBS4). Three families were assigned to the BBSl locus. The finding of linkage disequilibrium resulted in the assignment of three additional BBSl families and the refinement of the BBSl disease interval on chromosome 11q. One large family was linked to the relatively rare BBS3 locus and was used to confirm this locus and refine its map position on chromosome 3p. Six families were excluded from all previously mapped loci. A genomewide scan was used to successfully map the fifth locus, BBSS, to chromosome 2q31. In summary, of the 22 Newfoundland BBS families, six (27%) have been unambiguously assigned to BBSl, one to BBS3 (5%) • and one to BBSS (5%), suggesting that the relatively high prevalence of BBS in Newfoundland is the result of a minimum of three BBS genes and a BBSl founder.
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