A founder effect in the Newfoundland population reduces the Bardet-Biedl syndrome I (BBS1) interval to 1 cM

Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive disorder; major phenotypic findings include dysmorphic extremities, retinal dystrophy, obes ity, male hypogenitalism, and renal anomalies. In the majority of northern European families with BBS, the syndrome is linked to a 26-cM region on chr omosome 11q13. However, the finding, so far, of five distinct BBS loci (BBS 1, 1q; BBS2, 16q; BBS3, 3p; BBS4, 15q; BBS5, 2q) has hampered the positiona l cloning of these genes. We use linkage disequilibrium (LD) mapping in an isolated founder population in Newfoundland to significantly reduce the BBS 1 critical region. Extensive haplotyping in several unrelated BBS families of English descent revealed that the affected members were homozygous for o verlapping portions of a rare, disease-associated ancestral haplotype on ch romosome 11q13. The LD data suggest that the BBS1 gene lies in a 1-Mb, sequ ence-ready region on chromosome 11q13, which should enable its identificati on.