Localization of multiple pleiotropic genes for lipoprotein metabolism in baboons.

TitleLocalization of multiple pleiotropic genes for lipoprotein metabolism in baboons.
Publication TypeJournal Article
Year of Publication2009
AuthorsRainwater, DL, Cox, LA, Rogers, J, VandeBerg, JL, Mahaney, MC
JournalJ Lipid Res
Volume50
Issue7
Pagination1420-8
Date Published2009 Jul
ISSN1539-7262
KeywordsAnimals, Chromosomes, Mammalian, Diet, Gene Expression Regulation, Genetic Linkage, Genotype, Humans, Lipid Metabolism, Lipids, Lipoproteins, Lod Score, Multigene Family, Papio, Quantitative Trait Loci
Abstract

We employed a novel approach to identify the key loci that harbor genes influencing lipoprotein metabolism in approximately 2,000 pedigreed baboons fed various diets differing in levels of fat and cholesterol. In this study, 126 overlapping traits related to both LDL and HDL metabolism were normalized and subjected to genome-wide linkage screening. As was expected, the traits were highly, but not completely, correlated. We exploited the information in these correlated traits by focusing on those genomic regions harboring quantitative trait loci (QTL) for multiple traits, reasoning that the more influential genes would impact a larger number of traits. This study identified five major QTL clusters (each with at least two significant logarithm of the odds scores >4.7), two of which had not been previously reported in baboons. One of these mapped to the baboon ortholog of human chromosome 1p32-p34 and influenced concentrations of LDL-cholesterol on Basal and high-fat, low-cholesterol diets. The other novel QTL cluster mapped to the baboon ortholog of human chromosome 12q13.13-q14.1 and influenced LDL size properties on high-fat, low-cholesterol and high-fat, high-cholesterol, but not Basal, diets. Confirming the value of this approach, three of the QTL clusters replicated published linkage findings for the same or similar traits.

DOI10.1194/jlr.M800583-JLR200
Alternate JournalJ. Lipid Res.
PubMed ID19270339
PubMed Central IDPMC2694340
Grant ListC06 RR-13556 / RR / NCRR NIH HHS / United States
P51 RR-013986 / RR / NCRR NIH HHS / United States
C06 RR-014578 / RR / NCRR NIH HHS / United States
C06 RR-017515 / RR / NCRR NIH HHS / United States
C06 RR-17332 / RR / NCRR NIH HHS / United States
P01 HL-028972 / HL / NHLBI NIH HHS / United States
C06 RR-15456 / RR / NCRR NIH HHS / United States