Journal article
Regulation of gene expression in the mammalian eye and its relevance to eye disease
Proceedings of the National Academy of Sciences - PNAS, Vol.103(39), pp.14429-14434
09/26/2006
DOI: 10.1073/pnas.0602562103
PMCID: PMC1636701
PMID: 16983098
Abstract
We used expression quantitative trait locus mapping in the laboratory rat (Rattus norvegicus) to gain a broad perspective of gene regulation in the mammalian eye and to identify genetic variation relevant to human eye disease. Of >31,000 gene probes represented on an Affymetrix expression microarray, 18,976 exhibited sufficient signal for reliable analysis and at least 2-fold variation in expression among 120 F(2) rats generated from an SR/JrHsd x SHRSP intercross. Genome-wide linkage analysis with 399 genetic markers revealed significant linkage with at least one marker for 1,300 probes (alpha = 0.001; estimated empirical false discovery rate = 2%). Both contiguous and noncontiguous loci were found to be important in regulating mammalian eye gene expression. We investigated one locus of each type in greater detail and identified putative transcription-altering variations in both cases. We found an inserted cREL binding sequence in the 5' flanking sequence of the Abca4 gene associated with an increased expression level of that gene, and we found a mutation of the gene encoding thyroid hormone receptor beta2 associated with a decreased expression level of the gene encoding short-wavelength sensitive opsin (Opn1sw). In addition to these positional studies, we performed a pairwise analysis of gene expression to identify genes that are regulated in a coordinated manner and used this approach to validate two previously undescribed genes involved in the human disease Bardet-Biedl syndrome. These data and analytical approaches can be used to facilitate the discovery of additional genes and regulatory elements involved in human eye disease.
Details
- Title: Subtitle
- Regulation of gene expression in the mammalian eye and its relevance to eye disease
- Creators
- Todd E Scheetz - Departments of Ophthalmology and Biomedical Engineering, Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USAKwang-Youn A Kim - University of IowaRuth E SwiderskiAlisdair R PhilpTerry A BraunKevin L KnudtsonAnne M DorranceGerald F DiBonaJian HuangThomas L CasavantVal C SheffieldEdwin M Stone
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.103(39), pp.14429-14434
- DOI
- 10.1073/pnas.0602562103
- PMID
- 16983098
- PMCID
- PMC1636701
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- United States
- Language
- English
- Date published
- 09/26/2006
- 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; Internal Medicine; Ophthalmology and Visual Sciences; Iowa Institute of Human Genetics
- Record Identifier
- 9983979963902771
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