May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Analysis of Correlated Gene Expression in a Large Cohort of Rats Assists the Discovery of Two New Genes Involved in Bardet Biedl Syndrome (BBS)
E.M. Stone; A.P. Chiang; T. Scheetz; K.A. Kim; R.E. Swiderski; D.Y. Nishimura; L.M. Affatigato; J. Huang; T.L. Casavant; V.C. Sheffield
Author Affiliations & Notes
  • E.M. Stone
    The Carver College of Medicine at The University of Iowa, Iowa City, IA
    Ophthalmology and Visual Science, Electrical and Computer Engineering,
    The Howard Hughes Medical Institute, Iowa City, IA
  • A.P. Chiang
    Ophthalmology and Visual Science, Electrical and Computer Engineering,
    The University of Iowa, Iowa City, IA
  • T. Scheetz
    The Carver College of Medicine at The University of Iowa, Iowa City, IA
    Ophthalmology and Visual Science, Electrical and Computer Engineering,
    Pediatrics, Biomedical Engineering,
    The University of Iowa, Iowa City, IA
  • K.A. Kim
    Biostatistics,
    The University of Iowa, Iowa City, IA
  • R.E. Swiderski
    The Carver College of Medicine at The University of Iowa, Iowa City, IA
    Pediatrics, Biomedical Engineering,
  • D.Y. Nishimura
    The Carver College of Medicine at The University of Iowa, Iowa City, IA
    Pediatrics, Biomedical Engineering,
  • L.M. Affatigato
    The Carver College of Medicine at The University of Iowa, Iowa City, IA
    Ophthalmology and Visual Science, Electrical and Computer Engineering,
  • J. Huang
    Biostatistics,
    The University of Iowa, Iowa City, IA
  • T.L. Casavant
    Ophthalmology and Visual Science, Electrical and Computer Engineering,
    Pediatrics, Biomedical Engineering,
    The University of Iowa, Iowa City, IA
  • V.C. Sheffield
    The Carver College of Medicine at The University of Iowa, Iowa City, IA
    Pediatrics, Biomedical Engineering,
    The Howard Hughes Medical Institute, Iowa City, IA
  • Footnotes
    Commercial Relationships  E.M. Stone, None; A.P. Chiang, None; T. Scheetz, None; K.A. Kim, None; R.E. Swiderski, None; D.Y. Nishimura, None; L.M. Affatigato, None; J. Huang, None; T.L. Casavant, None; V.C. Sheffield, None.
  • Footnotes
    Support  FFB, HHMI, NEI Grant EY–11298
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 5919. doi:
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      E.M. Stone, A.P. Chiang, T. Scheetz, K.A. Kim, R.E. Swiderski, D.Y. Nishimura, L.M. Affatigato, J. Huang, T.L. Casavant, V.C. Sheffield; Analysis of Correlated Gene Expression in a Large Cohort of Rats Assists the Discovery of Two New Genes Involved in Bardet Biedl Syndrome (BBS) . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5919.

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Abstract

Purpose: : To investigate the hypothesis that functionally related genes will exhibit coordinated variation of expression in response to the genetic permutation associated with a cross of distantly–related, highly–inbred rat strains.

Methods: : Two inbred strains of laboratory rats (SR/JR/HSD and SHR/SP) were crossed and the resultant F1 animals were inter–crossed. At 12 weeks of age, 120 healthy males of the resulting F2 generation were euthanized. RNA was extracted from the eyes and genomic DNA was extracted from the liver of each animal. The ocular gene expression of each animal was determined using Affymetrix GeneChip Rat Genome 230 2.0 Arrays, which contain 31099 probes. Pairwise correlation of gene expression was investigated both as a marker of biological pathway membership and as a means of identifying new disease genes.

Results: : Eight genes previously known to cause BBS showed much higher correlation of expression than randomly selected expressed genes among the 120 F2 animals. When a number of candidate genes for BBS were evaluated for correlated expression with the eight known BBS genes, two new genes (B1 and TRIM32) exhibited greater correlation than the others. Screening of the coding sequences of these genes in BBS patients revealed disease–causing mutations.

Conclusions: : As organisms evolve, there is an evolutionary advantage in linking the expression of functionally related genes to the biological situations for which their functions are needed. The evolutionary conservation of these correlated control mechanisms provides a means of detecting functional relationships among groups of genes. Thus, the analysis of gene expression in the progeny of a large genetic cross can be used to find new genes responsible for genetically heterogeneous diseases like BBS.

Keywords: genetics • gene/expression • gene microarray 
© 2006, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2024 Association for Research in Vision and Ophthalmology.
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