title: Mutation spectrum in BBS genes guided by homozygosity mapping in an Indian cohort.
abstract: Bardet-Biedl syndrome (BBS), a ciliopathy disorder with pleiotropic effect manifests primarily as retinal degeneration along with renal insufficiency, polydactyly and obesity. In this study, we have performed homozygosity mapping using NspI 250K affymetrix gene chip followed by mutation screening of the candidate genes located in the homozygous blocks. These regions are prioritized based on the block length and candidature of the genes in BBS and other ciliopathies. Gene alterations in known BBS (22) and other ciliopathy genes such as ALMS1 (2) were seen in 24 of 30 families (80%). Mutations in BBS3 gene, inclusive of a novel recurrent mutation (p.I91T) accounted for 18% of the identified variations. Disease associated polymorphisms p.S70N (BBS2), rs1545 and rs1547 (BBS6) were also observed. This is the first study in Indian BBS patients and homozygosity mapping has proved to be an effective tool in prioritizing the candidate genes in consanguineous pedigrees. The study reveals a different mutation profile in the ciliopathy genes in Indian population and implication of novel loci/genes in 20% of the study group.
authors.affiliation: SN ONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, Tamilnadu, India; School of Chemical engineering and Biotechnology, SASTRA University, Thanjavur, Tamilnadu, India.
authors.forename: C
authors.initials: C
authors.lastname: Sathya Priya
authors.forename: P
authors.initials: P
authors.lastname: Sen
authors.forename: V
authors.initials: V
authors.lastname: Umashankar
authors.forename: N
authors.initials: N
authors.lastname: Gupta
authors.forename: M
authors.initials: M
authors.lastname: Kabra
authors.forename: G
authors.initials: G
authors.lastname: Kumaramanickavel
authors.forename: C
authors.initials: C
authors.lastname: Stoetzel
authors.forename: H
authors.initials: H
authors.lastname: Dollfus
authors.forename: S
authors.initials: S
authors.lastname: Sripriya
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics*; D020788:Bardet-Biedl Syndrome / Q000235:genetics* / Q000503:physiopathology; D018797:Cell Cycle Proteins; D018833:Chaperonins; D002874:Chromosome Mapping; D003598:Cytoskeletal Proteins; D005260:Female; D056726:Genetic Association Studies; D056385:Group II Chaperonins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007194:India; D008297:Male; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D051437:Renal Insufficiency / Q000235:genetics / Q000503:physiopathology; D012162:Retinal Degeneration / Q000235:genetics / Q000503:physiopathology
chemical_list: C490729:ALMS1 protein, human; C512111:BBS10 protein, human; C472639:BBS9 protein, human; C473309:Bbs2 protein, human; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D018833:Chaperonins; D056385:Group II Chaperonins; C491435:ARL6 protein, human; D020727:ADP-Ribosylation Factors
keywords: Bardet-Biedl syndrome; India; ciliopathy; gene screening; homozygosity mapping