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Physiol. Genomics (December 30, 2003). doi:10.1152/physiolgenomics.00142.2003
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Submitted on August 28, 2003
Accepted on December 26, 2003

Quantitative Trait Loci That Determine Lipoprotein Cholesterol Levels in an Intercross of 129S1/SvImJ and CAST/Ei Inbred Mice

Malcolm A Lyons1, Henning Wittenburg2, Renhua Li1, Kenneth A Walsh1, Ron Korstanje1, Gary A Churchill1, Martin C Carey3, and Beverly Paigen1*

1 The Jackson Laboratory, Bar Harbor, ME, USA
2 The Jackson Laboratory, Bar Harbor, ME, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Division of Gastroenterology, Brigham & Women's Hospital, Boston, MA, USA
3 Department of Medicine, Harvard Medical School, Boston, MA, USA; Division of Gastroenterology, Brigham & Women's Hospital, Boston, MA, USA

* To whom correspondence should be addressed. E-mail: bjp{at}jax.org.

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, in order 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.




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