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

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...

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Bibliographic Details
Published in:Physiological genomics 2004-03, Vol.17 (1), p.60-68
Main Authors: Lyons, Malcolm A, Wittenburg, Henning, Li, Renhua, Walsh, Kenneth A, Korstanje, Ron, Churchill, Gary A, Carey, Martin C, Paigen, Beverly
Format: Article
Language:English
Subjects:
Alleles
Animals
ATP Binding Cassette Transporter 1
ATP-Binding Cassette Transporters - genetics
Cholesterol, HDL - blood
Chromosome Mapping - methods
Chromosomes - genetics
Crosses, Genetic
Female
Gene Expression Regulation - genetics
Genetic Linkage - genetics
Lipoprotein Lipase - genetics
Liver - chemistry
Liver - metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Inbred Strains
Quantitative Trait Loci - genetics
RNA, Messenger - genetics
X Chromosome - genetics
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Summary: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
ISSN:1094-8341
1531-2267
DOI:10.1152/physiolgenomics.00142.2003