Genomic analysis of metabolic pathway gene expression in mice.
BACKGROUND
A segregating population of (C57BL/6J x 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.


CONCLUSIONS
This study demonstrates that genetic and gene-expression data can be integrated to identify pathways associated with clinical traits and their underlying genetic determinants.
Ghazalpour
Anatole
A
Department of Human Genetics, Molecular Biology Institute, University of California, Los Angeles, CA 90095-1679, USA. aghazalp@ucla.edu
Doss
Sudheer
S
Sheth
Sonal S
SS
Ingram-Drake
Leslie A
LA
Schadt
Eric E
EE
Lusis
Aldons J
AJ
Drake
Thomas A
TA
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000235:genetics; D002874:Chromosome Mapping; D005786:Gene Expression Regulation; D023281:Genomics; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008957:Models, Genetic; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D040641:Quantitative Trait Loci