Genome-level analysis of genetic regulation of liver gene expression networks

Authors

  • Daniel Gatti,

    1. Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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    • These authors contributed equally to this work.

  • Akira Maki,

    1. Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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    • These authors contributed equally to this work.

  • Elissa J. Chesler,

    1. Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN
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    • These authors contributed equally to this work.

  • Roumyana Kirova,

    1. Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN
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  • Oksana Kosyk,

    1. Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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  • Lu Lu,

    1. Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN
    2. Key Laboratory of Nerve Regeneration, Nantong University, Nantong, People's Republic of China
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  • Kenneth F. Manly,

    1. Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN
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  • Robert W. Williams,

    1. Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN
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  • Andy Perkins,

    1. Department of Computer Science, University of Tennessee, Knoxville, TN
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  • Michael A. Langston,

    1. Department of Computer Science, University of Tennessee, Knoxville, TN
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  • David W. Threadgill,

    1. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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    • Equally contributing senior author.

  • Ivan Rusyn

    Corresponding author
    1. Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
    • Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina at Chapel Hill, CB 7431, Chapel Hill, NC 27599
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    • Equally contributing senior author.

    • fax: 919-843-2596


  • Potential conflict of interest: Nothing to report.

Abstract

The liver is the primary site for the metabolism of nutrients, drugs, and chemical agents. Although metabolic pathways are complex and tightly regulated, genetic variation among individuals, reflected in variations in gene expression levels, introduces complexity into research on liver disease. This study dissected genetic networks that control liver gene expression through the combination of large-scale quantitative mRNA expression analysis with genetic mapping in a reference population of BXD recombinant inbred mouse strains for which extensive single-nucleotide polymorphism, haplotype, and phenotypic data are publicly available. We profiled gene expression in livers of naive mice of both sexes from C57BL/6J, DBA/2J, B6D2F1, and 37 BXD strains using Agilent oligonucleotide microarrays. These data were used to map quantitative trait loci (QTLs) responsible for variations in the expression of about 19,000 transcripts. We identified polymorphic local and distant QTLs, including several loci that control the expression of large numbers of genes in liver, by comparing the physical transcript position with the location of the controlling QTL. Conclusion: The data are available through a public web-based resource (www.genenetwork.org) that allows custom data mining, identification of coregulated transcripts and correlated phenotypes, cross-tissue, and cross-species comparisons, as well as testing of a broad array of hypotheses. (HEPATOLOGY 2007.)

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