title: Localization of genes for V+LDL plasma cholesterol levels on two diets in the opossum Monodelphis domestica.
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.
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA. cmk3@pitt.edu
authors.forename: Candace M
authors.initials: CM
authors.lastname: Kammerer
authors.forename: David L
authors.initials: DL
authors.lastname: Rainwater
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gouin
authors.forename: Madhuri
authors.initials: M
authors.lastname: Jasti
authors.forename: Kory C
authors.initials: KC
authors.lastname: Douglas
authors.forename: Amy S
authors.initials: AS
authors.lastname: Dressen
authors.forename: Prasanth
authors.initials: P
authors.lastname: Ganta
authors.forename: John L
authors.initials: JL
authors.lastname: Vandeberg
authors.forename: Paul B
authors.initials: PB
authors.lastname: Samollow
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015243:Cholesterol, VLDL / Q000097:blood* / Q000235:genetics; D004041:Dietary Fats / Q000494:pharmacology; D014644:Genetic Variation; D005838:Genotype; D050356:Lipid Metabolism / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D048309:Monodelphis / Q000235:genetics / Q000378:metabolism; D040641:Quantitative Trait Loci
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015243:Cholesterol, VLDL; D004041:Dietary Fats; D008565:Membrane Proteins