Regulation of gene expression in the mammalian eye and its relevance to eye disease

Todd E. Scheetz, Kwang Youn A. Kim, Ruth E. Swiderski, Alisdair R. Philp, Terry A. Braun, Kevin L. Knudtson, Anne M. Dorrance, Gerald F. DiBona, Jian Huang, Thomas L. Casavant, Val C. Sheffield, Edwin M. Stone

Research output: Journal article publicationJournal articleAcademic researchpeer-review

205 Citations (Scopus)


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 F2 rats generated from an SR/JrHsd × SHRSP intercross. Genome-wide linkage analysis with 399 genetic markers revealed significant linkage with at least one marker for 1,300 probes (α = 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 β2 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.
Original languageEnglish
Pages (from-to)14429-14434
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number39
Publication statusPublished - 26 Sept 2006
Externally publishedYes


  • Bioinformatics
  • Expression quantitative trait locus analysis
  • Gene regulation
  • Ophthalmology

ASJC Scopus subject areas

  • General


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