Localization of genes for V+LDL plasma cholesterol levels on two diets in the opossum Monodelphis domestica. Academic Article uri icon

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 x 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 x 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.

published proceedings

  • J Lipid Res

author list (cited authors)

  • Kammerer, C. M., Rainwater, D. L., Gouin, N., Jasti, M., Douglas, K. C., Dressen, A. S., ... Samollow, P. B.

citation count

  • 2

complete list of authors

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

publication date

  • October 2010