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Open Access Highly Accessed Research

Genomic analysis of metabolic pathway gene expression in mice

Anatole Ghazalpour1, Sudheer Doss1, Sonal S Sheth1, Leslie A Ingram-Drake2, Eric E Schadt3, Aldons J Lusis1 and Thomas A Drake2*

Author Affiliations

1 Department of Human Genetics, Department of Medicine and Department of Microbiology, Immunology and Molecular Genetics, and Molecular Biology Institute, University of California, Los Angeles, CA 90095-1679, USA

2 Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095-1732, USA

3 Rosetta Inpharmatics LLC, Kirkland, WA 98034, USA

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Genome Biology 2005, 6:R59  doi:10.1186/gb-2005-6-7-r59

Published: 1 July 2005

Abstract

Background

A segregating population of (C57BL/6J × DBA/2J)F2 intercross mice was studied for obesity-related traits and for global gene expression in liver. Quantitative trait locus analyses were applied to the subcutaneous fat-mass trait and all gene-expression data. These data were then used to identify gene sets that are differentially perturbed in lean and obese mice.

Results

We integrated global gene-expression data with phenotypic and genetic segregation analyses to evaluate metabolic pathways associated with obesity. Using two approaches we identified 13 metabolic pathways whose genes are coordinately regulated in association with obesity. Four genomic regions on chromosomes 3, 6, 16, and 19 were found to control the coordinated expression of these pathways. Using criteria that included trait correlation, differential gene expression, and linkage to genomic regions, we identified novel genes potentially associated with the identified pathways.

Conclusion

This study demonstrates that genetic and gene-expression data can be integrated to identify pathways associated with clinical traits and their underlying genetic determinants.