title: Autozygosity mapping of Bardet-Biedl syndrome to 12q21.2 and confirmation of FLJ23560 as BBS10.
abstract: Bardet-Biedl syndrome (BBS) is a genetically heterogeneous autosomal recessive disorder characterized by variable obesity, pigmentary retinopathy, polydactyly, mental retardation, hypogonadism and renal failure. In order to identify novel BBS loci we undertook autozygosity mapping studies using high-density SNP microarrays in consanguineous kindreds. We mapped a BBS locus to a 10.1 Mb region at 12q15-q21.2 in a large Omani BBS family (peak lod score 8.3 at theta = 0.0 for marker D12S1722) that contained the recently described BBS10 locus. Mutation analysis of candidate genes within the target interval, including the BBS10 gene, revealed a homozygous frameshift mutation in FLJ23560 and mutations were also detected in four smaller consanguineous families with regions of autozygosity at 12q21.2. These findings (a) confirm a previous report that FLJ23560 (BBS10) mutations are a significant cause of BBS, and (b) further demonstrate the utility of high-density SNP array mapping in consanguineous families for the mapping and identification of recessive disease genes.
authors.affiliation: Department of Medical and Molecular Genetics, School of Medicine, Institute of Biomedical Research, University of Birmingham, Birmingham, UK.
authors.forename: Dominic R A
authors.initials: DR
authors.lastname: White
authors.forename: Anuradha
authors.initials: A
authors.lastname: Ganesh
authors.forename: Darryl
authors.initials: D
authors.lastname: Nishimura
authors.forename: Eleanor
authors.initials: E
authors.lastname: Rattenberry
authors.forename: Shakeel
authors.initials: S
authors.lastname: Ahmed
authors.forename: Ursula M
authors.initials: UM
authors.lastname: Smith
authors.forename: Shanaz
authors.initials: S
authors.lastname: Pasha
authors.forename: Sandy
authors.initials: S
authors.lastname: Raeburn
authors.forename: Richard C
authors.initials: RC
authors.lastname: Trembath
authors.forename: Anna
authors.initials: A
authors.lastname: Rajab
authors.forename: Fiona
authors.initials: F
authors.lastname: Macdonald
authors.forename: Eyal
authors.initials: E
authors.lastname: Banin
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.forename: Colin A
authors.initials: CA
authors.lastname: Johnson
authors.forename: Val C
authors.initials: VC
authors.lastname: Sheffield
authors.forename: Eamonn R
authors.initials: ER
authors.lastname: Maher
mesh_terms: D000328:Adult; D020788:Bardet-Biedl Syndrome / Q000235:genetics*; D018833:Chaperonins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D056385:Group II Chaperonins; D006720:Homozygote; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D009850:Oman; D010375:Pedigree; D020161:Physical Chromosome Mapping; D020641:Polymorphism, Single Nucleotide
chemical_list: C512111:BBS10 protein, human; D018833:Chaperonins; D056385:Group II Chaperonins