Localization of genes for V+LDL plasma cholesterol levels on two diets in the opossum Monodelphis domestica

Candace M. Kammerer, David L. Rainwater, Nicolas Gouin, Madhuri Jasti, Kory C. Douglas, Amy S. Dressen, Prasanth Ganta, John L. VandeBerg, Paul B. Samollow

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    2 Scopus citations

    Abstract

    Plasma cholesterol levels among individuals vary considerably in response to diet. However, the genes that influence this response are largely unknown. Non-HDL (V+LDL) cholesterol levels vary dramatically among gray, short-tailed opossums fed an atherogenic diet, and we previously reported that two quantitative trait loci (QTLs) influenced V+LDL cholesterol on two diets. We used hypothesis-free, genome-wide linkage analyses on data from 325 pedigreed opossums and located one QTL for V+LDL cholesterol on the basal diet on opossum chromosome 1q [logarithm of the odds (LOD) = 3.11, genomic P = 0.019] and another QTL for V+LDL on the atherogenic diet (i.e., high levels of cholesterol and fat) on chromosome 8 (LOD = 9.88, genomic P = 5 × 10-9). We then employed a novel strategy involving combined analyses of genomic resources, expression analysis, sequencing, and genotyping to identify candidate genes for the chromosome 8 QTL. A polymorphism in ABCB4 was strongly associated (P = 9 × 10-14) with the plasma V+LDL cholesterol concentrations on the high-cholesterol, high-fat diet. The results of this study indicate that genetic variation in ABCB4, or closely linked genes, is responsible for the dramatic differences among opossums in their V+LDL cholesterol response to an atherogenic diet.

    Original languageEnglish (US)
    Pages (from-to)2929-2939
    Number of pages11
    JournalJournal of lipid research
    Volume51
    Issue number10
    DOIs
    StatePublished - Oct 1 2010

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    Keywords

    • Animal model
    • Comparative synteny
    • Diet
    • Genes
    • Very low plus low-density lipoprotein-cholesterol

    ASJC Scopus subject areas

    • Biochemistry
    • Endocrinology
    • Cell Biology

    Cite this

    Kammerer, C. M., Rainwater, D. L., Gouin, N., Jasti, M., Douglas, K. C., Dressen, A. S., Ganta, P., VandeBerg, J. L., & Samollow, P. B. (2010). Localization of genes for V+LDL plasma cholesterol levels on two diets in the opossum Monodelphis domestica. Journal of lipid research, 51(10), 2929-2939. https://doi.org/10.1194/jlr.M005686