Autozygosity mapping of Bardet-Biedl syndrome to 12q21.2 and confirmation of FLJ23560 as BBS10.
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.
White
Dominic R A
DR
Department of Medical and Molecular Genetics, School of Medicine, Institute of Biomedical Research, University of Birmingham, Birmingham, UK.
Ganesh
Anuradha
A
Nishimura
Darryl
D
Rattenberry
Eleanor
E
Ahmed
Shakeel
S
Smith
Ursula M
UM
Pasha
Shanaz
S
Raeburn
Sandy
S
Trembath
Richard C
RC
Rajab
Anna
A
Macdonald
Fiona
F
Banin
Eyal
E
Stone
Edwin M
EM
Johnson
Colin A
CA
Sheffield
Val C
VC
Maher
Eamonn R
ER
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
C512111:BBS10 protein, human; D018833:Chaperonins; D056385:Group II Chaperonins