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Applying Gene Expression, Proteomics and Single-Nucleotide Polymorphism Analysis for Complex Trait Gene Identification

Ioannis M. Stylianou, Jason P. Affourtit, Keith R. Shockley, Robert Y. Wilpan, Fadi A. Abdi, Sanjeev Bhardwaj, Jarod Rollins, Gary A Churchill and Beverly Paigen
Genetics March 1, 2008 vol. 178 no. 3 1795-1805; https://doi.org/10.1534/genetics.107.081216
Ioannis M. Stylianou
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Jason P. Affourtit
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Keith R. Shockley
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Robert Y. Wilpan
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Fadi A. Abdi
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Sanjeev Bhardwaj
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Jarod Rollins
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Gary A Churchill
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Beverly Paigen
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Abstract

Previous quantitative trait locus (QTL) analysis of an intercross involving the inbred mouse strains NZB/BlNJ and SM/J revealed QTL for a variety of complex traits. Many QTL have large intervals containing hundreds of genes, and methods are needed to rapidly sort through these genes for probable candidates. We chose nine QTL: the three most significant for high-density lipoprotein (HDL) cholesterol, gallstone formation, and obesity. We searched for candidate genes using three different approaches: mRNA microarray gene expression technology to assess >45,000 transcripts, publicly available SNPs to locate genes that are not identical by descent and that contain nonsynonymous coding differences, and a mass-spectrometry-based proteomics technology to interrogate nearly 1000 proteins for differential expression in the liver of the two parental inbred strains. This systematic approach reduced the number of candidate genes within each QTL from hundreds to a manageable list. Each of the three approaches selected candidates that the other two approaches missed. For example, candidate genes such as Apoa2 and Acads had differential protein levels although the mRNA levels were similar. We conclude that all three approaches are important and that focusing on a single approach such as mRNA expression may fail to identify a QTL gene.

Footnotes

  • ↵1 Present address: University of Pennsylvania, School of Medicine, Institute for Translational Medicine and Therapeutics, Philadelphia, PA 19104-6160.

  • ↵2 Present address: 454 Life Sciences, Branford, CT 06405.

  • Communicating editor: K. W. Broman

  • Received August 28, 2007.
  • Accepted January 16, 2008.
  • Copyright © 2008 by the Genetics Society of America
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PUBLICATION INFORMATION

Volume 178 Issue 3, March 2008

Genetics: 178 (3)

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Genetics of complex traits
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Applying Gene Expression, Proteomics and Single-Nucleotide Polymorphism Analysis for Complex Trait Gene Identification

Ioannis M. Stylianou, Jason P. Affourtit, Keith R. Shockley, Robert Y. Wilpan, Fadi A. Abdi, Sanjeev Bhardwaj, Jarod Rollins, Gary A Churchill and Beverly Paigen
Genetics March 1, 2008 vol. 178 no. 3 1795-1805; https://doi.org/10.1534/genetics.107.081216
Ioannis M. Stylianou
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Jason P. Affourtit
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Keith R. Shockley
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Robert Y. Wilpan
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Fadi A. Abdi
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Sanjeev Bhardwaj
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Jarod Rollins
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Gary A Churchill
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Beverly Paigen
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Citation

Applying Gene Expression, Proteomics and Single-Nucleotide Polymorphism Analysis for Complex Trait Gene Identification

Ioannis M. Stylianou, Jason P. Affourtit, Keith R. Shockley, Robert Y. Wilpan, Fadi A. Abdi, Sanjeev Bhardwaj, Jarod Rollins, Gary A Churchill and Beverly Paigen
Genetics March 1, 2008 vol. 178 no. 3 1795-1805; https://doi.org/10.1534/genetics.107.081216
Ioannis M. Stylianou
  • Find this author on Google Scholar
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Jason P. Affourtit
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Keith R. Shockley
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Robert Y. Wilpan
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Fadi A. Abdi
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Sanjeev Bhardwaj
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Jarod Rollins
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Gary A Churchill
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Beverly Paigen
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