Homozygosity and Linkage-Disequilibrium Mapping of Bardet-Biedl Syndrome Type 1 (BBS1). T. Young¹, M.O. Woods¹, P.S. Parfrey¹, J.S. Green¹, D. Hefferton¹, W.S. Davidson². 1) Fac Medicine, Memorial Univ Newfoundland, St John's, NF, Canada; 2) Dept Biochem, Memorial Univ Newfoundland, St John's, NF, Canada.

   Bardet-Biedl syndrome (BBS; OMIM 209900) is a rare, autosomal recessive disorder of unknown etiology that exhibits phenotypic and genetic heterogeneity. The syndrome is characterized by retinal dystrophy, dysmorphic extremities, obesity, male hypogenitalism and renal anomalies. Five genetic loci have been mapped by genome-wide scanning in (i) a collection of North American families of North European descent (BBS1, 11q); (ii) three unrelated Bedouin kindreds from Kuwait (BBS2, 16q; BBS3, 3p; BBS4, 15q); (iii) a kindred of North European descent from Newfoundland, Canada (BBS5, 2q). So far, none of the BBS genes have been cloned. We have extended haplotypes within the 13 cM BBS1 critical region for 10 BBS patients and their families representing three BBS1-linked and three unassigned families from the recently founded Newfoundland population. All 10 patients were homozygous for overlapping portions of a rare, disease-associated ancestral haplotype. Linkage disequilibrium analysis of the overlapping ancestral haplotypes significantly reduced the BBS1 critical region and should aid in the positional cloning of the BBS1 gene.