Localization of genes for V+LDL plasma cholesterol levels on two diets in the opossum Monodelphis domestica.
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.
Kammerer
Candace M
CM
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA. cmk3@pitt.edu
Rainwater
David L
DL
Gouin
Nicolas
N
Jasti
Madhuri
M
Douglas
Kory C
KC
Dressen
Amy S
AS
Ganta
Prasanth
P
Vandeberg
John L
JL
Samollow
Paul B
PB
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
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015243:Cholesterol, VLDL; D004041:Dietary Fats; D008565:Membrane Proteins