title: A founder effect in the newfoundland population reduces the Bardet-Biedl syndrome I (BBS1) interval to 1 cM.
abstract: Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive disorder; major phenotypic findings include dysmorphic extremities, retinal dystrophy, obesity, male hypogenitalism, and renal anomalies. In the majority of northern European families with BBS, the syndrome is linked to a 26-cM region on chromosome 11q13. However, the finding, so far, of five distinct BBS loci (BBS1, 1q; BBS2, 16q; BBS3, 3p; BBS4, 15q; BBS5, 2q) has hampered the positional cloning of these genes. We use linkage disequilibrium (LD) mapping in an isolated founder population in Newfoundland to significantly reduce the BBS1 critical region. Extensive haplotyping in several unrelated BBS families of English descent revealed that the affected members were homozygous for overlapping portions of a rare, disease-associated ancestral haplotype on chromosome 11q13. The LD data suggest that the BBS1 gene lies in a 1-Mb, sequence-ready region on chromosome 11q13, which should enable its identification.
authors.affiliation: Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland A1B 3V9, Canada. tlyoung@morgan.ucs.mun.ca.
authors.forename: T L
authors.initials: TL
authors.lastname: Young
authors.forename: M O
authors.initials: MO
authors.lastname: Woods
authors.forename: P S
authors.initials: PS
authors.lastname: Parfrey
authors.forename: J S
authors.initials: JS
authors.lastname: Green
authors.forename: D
authors.initials: D
authors.lastname: Hefferton
authors.forename: W S
authors.initials: WS
authors.lastname: Davidson
mesh_terms: D000483:Alleles; D020788:Bardet-Biedl Syndrome / Q000235:genetics*; D000075002:Bestrophins; D018118:Chloride Channels; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D003241:Consanguinity; D004739:England; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D018703:Founder Effect; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics; D009523:Newfoundland and Labrador; D010375:Pedigree; D011518:Proto-Oncogene Proteins
chemical_list: C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins; C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins