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Originally published In Press as doi:10.1194/jlr.M400136-JLR200 on August 16, 2004

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Journal of Lipid Research, Vol. 45, 2063-2070, November 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Epistatic interaction between two nonstructural loci on chromosomes 7 and 3 influences hepatic lipase activity in BSB mice

Nengjun Yi*,{dagger}, Sally Chiu§, David B. Allison*,{dagger}, Janis S. Fisler** and Craig H. Warden1,§,{dagger}{dagger}

* Department of Biostatistics, Section on Statistical Genetics, University of Alabama, Birmingham, AL 35294
{dagger} Clinical Nutrition Research Center, University of Alabama, Birmingham, AL 35294
§ Rowe Program in Genetics, University of California, Davis, CA 95616
** Department of Nutrition, University of California, Davis, CA 95616
{dagger}{dagger} Department of Pediatrics and Section of Neurobiology, Physiology, and Behavior, University of California, Davis, CA 95616

1 To whom correspondence should be addressed. e-mail: chwarden{at}ucdavis.edu

BSB mice exhibit a wide range of obesity despite being produced by a backcross of lean C57BL/6J (B) x lean Mus spretus (SPRET/Pt) F1 animals x B. Previous linkage studies identified a quantitative trait locus (QTL) on mouse chromosome 7 with coincident peaks for hepatic lipase activity, obesity, and plasma cholesterol. However, these mice were not analyzed for gene x gene epistasis. Hepatic lipase activity is correlated with obesity and plasma cholesterol levels. In this study, we identified QTLs for plasma hepatic lipase activity with three statistical mapping methods: maximum likelihood interval mapping, Bayesian nonepistatic mapping, and Bayesian epistatic mapping. Bayesian epistatic mapping detected not only the QTL on chromosome 7 but also an additional QTL on chromosome 3, which has a weak main effect but a strong interaction with chromosome 7. SPRET/Pt alleles of the QTL on each chromosome promote hepatic lipase activity.

The proportion of phenotypic variance explained by the epistatic effect is higher than that explained by the main effect of the QTL on chromosome 7.

Abbreviations: cM, centimorgan; HPD, high posterior density; MCMC, Markov chain Monte Carlo; QTL, quantitative trait locus

Supplementary key words gene x gene • mouse • obesity • hepatic lipase • Bayesian • quantitative trait locus


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N. Yi, B. S. Yandell, G. A. Churchill, D. B. Allison, E. J. Eisen, and D. Pomp
Bayesian Model Selection for Genome-Wide Epistatic Quantitative Trait Loci Analysis
Genetics, July 1, 2005; 170(3): 1333 - 1344.
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