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Physiol. Genomics 37: 294-302, 2009. First published March 31, 2009; doi:10.1152/physiolgenomics.90245.2008
1094-8341/09 $8.00
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Received 9 May 2008; accepted in final form 26 March 2009.
Physiological Genomics 37:294-302 (2009)
1094-8341/09 $8.00 © 2009 American Physiological Society

Genetic dissection of a major mouse obesity QTL (Carfhg2): integration of gene expression and causality modeling

Charles R. Farber 1, Jason E. Aten 2, Emily A. Farber 3, Vincent de Vera 3, Rodrigo Gularte 3, Alma Islas-Trejo 3, Pengzi Wen 1, Steve Horvath 4,5, Michael Lucero 6, Aldons J. Lusis 1,2,7,8 and Juan F. Medrano 3

1 Department of Medicine, University of California Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles
2 Department of Human Genetics, University of California Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles
3 Department of Animal Science, University of California Davis, Davis
4 Department of Biomathematics, University of California Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles
5 Department of Biostatistics, School of Public Health, University of California Los Angeles, Los Angeles
6 Fluidigm Corporation, South San Francisco
7 Molecular Biology Institute, University of California Los Angeles
8 Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, California

HG.CAST-(D9Mit249-D9Mit133) (HG9) congenic mice are homozygous for CAST/EiJ chromosome (Chr) 9 alleles from ~9 to 84 Mbp on a C57BL6/J-hg/hg (HG) background. This region contains the carcass fat in high growth mice (Carfhg2) quantitative trait locus (QTL), and while its obesity-promoting effects have been confirmed in HG9 mice, its underlying genetic basis remains elusive. To refine the location of Carfhg2, we preformed a linkage analysis in two congenic F2 intercrosses and progeny-tested a recombinant F2 male. These analyses narrowed Carfhg2 to between 33.0 and 40.8 Mbp on Chr 9. To identify candidate genes we measured the expression of 44 transcripts surrounding the Carfhg2 peak in adipose, brain, liver, and muscle tissues from F2 mice using Biomark 48.48 Dynamic Arrays. In total, 68% (30 of the 44) of genes were regulated by a significant expression QTL (eQTL) in at least one tissue. To prioritize genes with eQTL we used Network Edge Orienting, a causality modeling tool. These analyses advance our goal of identifying the molecular basis of Carfhg2.

quantitative trait loci; congenic; genetics; complex traits







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