Systems Genetics of Metabolism: The Use of the BXD Murine Reference Panel for Multiscalar Integration of Traits

被引：163

作者：

Andreux, Penelope A. ^{[2
]}

Williams, Evan G. ^{[2
]}

Koutnikova, Hana ^{[3
]}

Houtkooper, Riekelt H. ^{[2
]}

Champy, Marie-France ^{[3
]}

Henry, Hugues ^{[4
]}

Schoonjans, Kristina ^{[2
]}

Williams, Robert W. ^{[1
]}

Auwerx, Johan ^{[2
,3
]}

机构：

[1] Univ Tennessee, Hlth Sci Ctr, Ctr Integrat & Translat Genom, Dept Anat & Neurobiol, Memphis, TN 38163 USA

[2] Ecole Polytech Fed Lausanne, Sch Life Sci, Lab Integrat & Syst Physiol, CH-1015 Lausanne, Switzerland

[3] Inst Clin Souris, F-67404 Illkirch Graffenstaden, France

[4] CHU Vaudois, CH-1011 Lausanne, Switzerland

来源：

CELL | 2012年 / 150卷 / 06期

基金：

瑞士国家科学基金会;

关键词：

INNATE IMMUNITY; COMPLEX TRAITS; DISSECTION; SUBSTITUTION; ASSOCIATION; REGULATOR; GENOMICS; VARIANT; LOCI; MASS;

D O I：

10.1016/j.cell.2012.08.012

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Metabolic homeostasis is achieved by complex molecular and cellular networks that differ significantly among individuals and are difficult to model with genetically engineered lines of mice optimized to study single gene function. Here, we systematically acquired metabolic phenotypes by using the EUMODIC EMPReSS protocols across a large panel of isogenic but diverse strains of mice (BXD type) to study the genetic control of metabolism. We generated and analyzed 140 classical phenotypes and deposited these in an open-access web service for systems genetics (www.genenetwork.org). Heritability, influence of sex, and genetic modifiers of traits were examined singly and jointly by using quantitative-trait locus (QTL) and expression QTL-mapping methods. Traits and networks were linked to loci encompassing both known variants and novel candidate genes, including alkaline phosphatase (ALPL), here linked to hypophosphatasia. The assembled and curated phenotypes provide key resources and exemplars that can be used to dissect complex metabolic traits and disorders.

引用

页码：1287 / 1299

页数：13

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