Journal article
Homozygosity mapping with SNP arrays identifies TRIM32, an E3 ubiquitin ligase, as a Bardet-Biedl syndrome gene (BBS11)
Proceedings of the National Academy of Sciences - PNAS, Vol.103(16), pp.6287-6292
04/18/2006
DOI: 10.1073/pnas.0600158103
PMCID: PMC1458870
PMID: 16606853
Abstract
The identification of mutations in genes that cause human diseases has largely been accomplished through the use of positional cloning, which relies on linkage mapping. In studies of rare diseases, the resolution of linkage mapping is limited by the number of available meioses and informative marker density. One recent advance is the development of high-density SNP microarrays for genotyping. The SNP arrays overcome low marker informativity by using a large number of markers to achieve greater coverage at finer resolution. We used SNP microarray genotyping for homozygosity mapping in a small consanguineous Israeli Bedouin family with autosomal recessive Bardet-Biedl syndrome (BBS; obesity, pigmentary retinopathy, polydactyly, hypogonadism, renal and cardiac abnormalities, and cognitive impairment) in which previous linkage studies using short tandem repeat polymorphisms failed to identify a disease locus. SNP genotyping revealed a homozygous candidate region. Mutation analysis in the region of homozygosity identified a conserved homozygous missense mutation in the TRIM32 gene, a gene coding for an E3 ubiquitin ligase. Functional analysis of this gene in zebrafish and expression correlation analyses among other BBS genes in an expression quantitative trait loci data set demonstrate that TRIM32 is a BBS gene. This study shows the value of high-density SNP genotyping for homozygosity mapping and the use of expression correlation data for evaluation of candidate genes and identifies the proteasome degradation pathway as a pathway involved in BBS.
Details
- Title: Subtitle
- Homozygosity mapping with SNP arrays identifies TRIM32, an E3 ubiquitin ligase, as a Bardet-Biedl syndrome gene (BBS11)
- Creators
- Annie P Chiang - Department of Electrical Engineering, University of Iowa, Iowa City, IA 52242, USAJohn S BeckHsan-Jan YenMarwan K TayehTodd E ScheetzRuth E SwiderskiDarryl Y NishimuraTerry A BraunKwang-Youn A Kim - University of IowaJian HuangKhalil ElbedourRivka CarmiDiane C SlusarskiThomas L CasavantEdwin M StoneVal C Sheffield
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.103(16), pp.6287-6292
- DOI
- 10.1073/pnas.0600158103
- PMID
- 16606853
- PMCID
- PMC1458870
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- 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
- 04/18/2006
- Academic Unit
- Statistics and Actuarial Science; Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Biology; Ophthalmology and Visual Sciences
- Record Identifier
- 9983980080902771
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