High-Resolution Association Mapping of Atherosclerosis Loci in Mice

被引：12

作者：

Bennett, Brian J. ^{[1
]}

Orozco, Luz ^{[3
]}

Kostem, Emrah ^{[5
]}

Erbilgin, Ayca ^{[4
]}

Dallinga, Marchien ^{[2
]}

Neuhaus, Isaac ^{[6
]}

Guan, Bo ^{[6
]}

Wang, Xuping ^{[2
]}

Eskin, Eleazar ^{[3
,5
]}

Lusis, Aldons J. ^{[2
,3
,4
]}

机构：

[1] Univ N Carolina, Dept Genet, Chapel Hill, NC USA

[2] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA

[3] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA

[4] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA

[5] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90024 USA

[6] Bristol Myers Squibb Co, Bioinformat, Pennington, NJ USA

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 2012年 / 32卷 / 08期

基金：

美国国家卫生研究院;

关键词：

atherosclerosis; gene expression; genetic techniques; genetically altered mice; E-DEFICIENT MICE; DENSITY-LIPOPROTEIN LEVELS; QUANTITATIVE TRAIT LOCI; RECEPTOR KNOCKOUT MICE; APOLIPOPROTEIN-E; MISSING HERITABILITY; SUSCEPTIBILITY LOCI; STRAINS C57BL/6J; HDL-CHOLESTEROL; INBRED STRAINS;

D O I：

10.1161/ATVBAHA.112.253864

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The purpose of this study was to fine map previously identified quantitative trait loci affecting atherosclerosis in mice using association analysis. Methods and Results-We recently showed that high-resolution association analysis using common inbred strains of mice is feasible if corrected for population structure. To use this approach for atherosclerosis, which requires a sensitizing mutation, we bred human apolipoprotein B-100 transgenic mice with 22 different inbred strains to produce F1 heterozygotes. Mice carrying the dominant transgene were tested for association with high-density single nucleotide polymorphism maps. Here, we focus on high-resolution mapping of the previously described atherosclerosis 30 locus on chromosome 1. Compared with the previous linkage analysis, association improved the resolution of the atherosclerosis 30 locus by more than an order of magnitude. Using expression quantitative trait locus analysis, we identified one of the genes in the region, desmin, as a strong candidate. Conclusion-Our high-resolution mapping approach accurately identifies and fine maps known atherosclerosis quantitative trait loci. These results suggest that high-resolution genome-wide association analysis for atherosclerosis is feasible in mice. (Arterioscler Thromb Vasc Biol. 2012;32:1790-1798.)

引用

页码：1790 / U216

页数：25

共 39 条

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