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Physiol. Genomics 17: 60-68, 2004. First published December 30, 2003; doi:10.1152/physiolgenomics.00142.2003
1094-8341/04 $5.00
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Received 28 August 2003; accepted in final form 26 December 2003.
Physiological Genomics 17:60-68 (2004)
1094-8341/04 $5.00 © 2004 American Physiological Society

Quantitative trait loci that determine lipoprotein cholesterol levels in an intercross of 129S1/SvImJ and CAST/Ei inbred mice

Malcolm A. Lyons1, Henning Wittenburg1,2, Renhua Li1, Kenneth A. Walsh1, Ron Korstanje1, Gary A. Churchill1, Martin C. Carey2 and Beverly Paigen1

1 The Jackson Laboratory, Bar Harbor, Maine 04609
2 Department of Medicine, Harvard Medical School, Division of Gastroenterology, Brigham and Women’s Hospital and Harvard Digestive Diseases Center, Boston, Massachusetts 02115

To identify genetic determinants of lipoprotein levels, we are performing quantitative trait locus (QTL) analysis on a series of mouse intercrosses in a "daisy chain" experimental design, to increase the power of detecting QTL and to identify common variants that should segregate in multiple intercrosses. In this study, we intercrossed strains CAST/Ei and 129S1/SvImJ, determined HDL, total, and non-HDL cholesterol levels, and performed QTL mapping using Pseudomarker software. For HDL cholesterol, we identified two significant QTL on chromosome (Chr) 1 (Hdlq5, 82 cM, 60–100 cM) and Chr 4 (Hdlq10, 20 cM, 10–30 cM). For total cholesterol, we identified three significant QTL on Chr 1 (Chol7, 74 cM, 65–80 cM), Chr 4 (Chol8, 12 cM, 0–30 cM), and Chr 17 (Chol9, 54 cM, 20–60 cM). For non-HDL cholesterol, we identified significant QTL on Chr 8 (Nhdlq1, 34 cM, 20–60 cM) and Chr X (Nhdlq2, 6 cM, 0–18 cM). Hdlq10 was the only QTL detected in two intercrosses involving strain CAST/Ei. Hdlq5, Hdlq10, Nhdlq1, and two suggestive QTL at D7Mit246 and D15Mit115 coincided with orthologous human lipoprotein QTL. Our analysis furthers the knowledge of the genetic control of lipoprotein levels and points to the importance of Hdlq10, which was detected repeatedly in multiple studies.

Castaneus; mouse; QTL; HDL; high-density lipopolysaccharide; genetics; Abca1; Lpl




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