Abstract
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.
Highlights
BSB mice exhibit a wide range of obesity despite being produced by a backcross of lean C57BL/6J (B) ؋ lean Mus spretus (SPRET/Pt) F1 animals ؋ B
These assays were used to identify a quantitative trait locus (QTL) where hepatic lipase activity was coincident with QTLs for plasma cholesterol and fat mass on mouse chromosome 7 [12, 13]
The underlying genes influencing the QTL remain unknown because the QTL does not include the hepatic lipase (Lipc) structural gene located on mouse chromosome 9
Summary
BSB mice exhibit a wide range of obesity despite being produced by a backcross of lean C57BL/6J (B) ؋ lean Mus spretus (SPRET/Pt) F1 animals ؋ 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. These mice were not analyzed for gene ؋ gene epistasis. Epistatic interaction between two nonstructural loci on chromosomes 7 and 3 influences hepatic lipase activity in BSB mice. Using the traditional interval QTL mapping method, previous studies identified only one QTL on chromosome 7 influencing plasma hepatic lipase activity [12, 13]. Discrete combinations of alleles of genes, or gene products, may interact with each other in markedly different
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