Journal article
Comparative genomics and gene expression analysis identifies BBS9, a new Bardet-Biedl syndrome gene
American journal of human genetics, Vol.77(6), pp.1021-1033
12/2005
DOI: 10.1086/498323
PMCID: PMC1285160
PMID: 16380913
Abstract
Bardet-Biedl syndrome (BBS) is an autosomal recessive, genetically heterogeneous, pleiotropic human disorder characterized by obesity, retinopathy, polydactyly, renal and cardiac malformations, learning disabilities, and hypogenitalism. Eight BBS genes representing all known mapped loci have been identified. Mutation analysis of the known BBS genes in BBS patients indicate that additional BBS genes exist and/or that unidentified mutations exist in the known genes. To identify new BBS genes, we performed homozygosity mapping of small, consanguineous BBS pedigrees, using moderately dense SNP arrays. A bioinformatics approach combining comparative genomic analysis and gene expression studies of a BBS-knockout mouse model was used to prioritize BBS candidate genes within the newly identified loci for mutation screening. By use of this strategy, parathyroid hormone-responsive gene B1 (B1) was found to be a novel BBS gene (BBS9), supported by the identification of homozygous mutations in BBS patients. The identification of BBS9 illustrates the power of using a combination of comparative genomic analysis, gene expression studies, and homozygosity mapping with SNP arrays in small, consanguineous families for the identification of rare autosomal recessive disorders. We also demonstrate that small, consanguineous families are useful in identifying intragenic deletions. This type of mutation is likely to be underreported because of the difficulty of deletion detection in the heterozygous state by the mutation screening methods that are used in many studies.
Details
- Title: Subtitle
- Comparative genomics and gene expression analysis identifies BBS9, a new Bardet-Biedl syndrome gene
- Creators
- Darryl Y Nishimura - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USARuth E SwiderskiCharles C SearbyErik M BergAmanda L FergusonRaoul HennekamSaul MerinRichard G WeleberLeslie G BieseckerEdwin M StoneVal C Sheffield
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.77(6), pp.1021-1033
- DOI
- 10.1086/498323
- PMID
- 16380913
- PMCID
- PMC1285160
- NLM abbreviation
- Am J Hum Genet
- ISSN
- 0002-9297
- eISSN
- 1537-6605
- Publisher
- United States
- Grant note
- R01 EY011298 / NEI NIH HHS P50-HL-55006 / NHLBI NIH HHS P50 HL055006 / NHLBI NIH HHS R01-EY-11298 / NEI NIH HHS
- Language
- English
- Date published
- 12/2005
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
- Record Identifier
- 9983980075902771
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