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Journal of Lipid Research, Vol. 50, 1420-1428, July 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Localization of multiple pleiotropic genes for lipoprotein metabolism in baboons

David L. Rainwater^1,*, Laura A. Cox^*,, Jeffrey Rogers^*,, John L. VandeBerg^*, and Michael C. Mahaney^*,

^* Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX 78245
Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, San Antonio, TX 78245

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of a table.

The research was supported by a grant (P01 HL-028972) from the National Institutes of Health; the primate resources were supported by National Institutes of Health Grant P51 RR-013986 to the Southwest National Primate Research Center; and the research was performed in facilities constructed with support from National Institutes of Health Grants C06 RR-13556, C06 RR-014578, C06 RR-15456, C06 RR-17332, and C06 RR-017515.

Published, JLR Papers in Press, March 8, 2009.

¹ To whom correspondence should be addressed. e-mail: david{at}sfbrgenetics.org

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.

Supplementary key words linkage analysis • quantitative trait locus • genetic • primate

Abbreviations: apo, apolipoprotein; HDL-C, HDL-cholesterol; HFHC, diet high in fat and cholesterol; HFLC, diet high in fat but low in cholesterol; IBD, identity-by-descent; LOD, logarithm of the odds; PON, paraoxonase; QTL, quantitative trait loci; TG, triglyceride

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