Genetic analysis of complex traits in the emerging Collaborative Cross

被引：256

作者：

Aylor, David L. ^{[1
]}

Valdar, William ^{[1
]}

Foulds-Mathes, Wendy ^{[1
]}

Buus, Ryan J. ^{[1
]}

Verdugo, Ricardo A. ^{[2
]}

Baric, Ralph S. ^{[3
,4
]}

Ferris, Martin T. ^{[1
]}

Frelinger, Jeff A. ^{[4
]}

Heise, Mark ^{[1
]}

Frieman, Matt B. ^{[4
]}

Gralinski, Lisa E. ^{[4
]}

Bell, Timothy A. ^{[1
]}

Didion, John D. ^{[1
]}

Hua, Kunjie ^{[1
]}

Nehrenberg, Derrick L. ^{[1
]}

Powell, Christine L. ^{[1
]}

Steigerwalt, Jill ^{[5
]}

Xie, Yuying ^{[1
]}

Kelada, Samir N. P. ^{[6
]}

Collins, Francis S. ^{[6
]}

Yang, Ivana V. ^{[7
]}

Schwartz, David A. ^{[7
]}

Branstetter, Lisa A. ^{[8
]}

Chesler, Elissa J. ^{[2
]}

Miller, Darla R. ^{[1
]}

Spence, Jason ^{[1
]}

Liu, Eric Yi ^{[9
]}

McMillan, Leonard ^{[9
]}

Sarkar, Abhishek ^{[9
]}

Wang, Jeremy ^{[9
]}

Wang, Wei ^{[9
]}

Zhang, Qi ^{[9
]}

Broman, Karl W. ^{[10
]}

Korstanje, Ron ^{[2
]}

Durrant, Caroline ^{[11
]}

Mott, Richard ^{[11
]}

Iraqi, Fuad A. ^{[12
]}

Pomp, Daniel ^{[1
]}

Threadgill, David ^{[5
]}

de Villena, Fernando Pardo-Manuel ^{[1
]}

Churchill, Gary A. ^{[2
]}

机构：

[1] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

[2] Jackson Lab, Bar Harbor, ME 04609 USA

[3] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA

[4] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA

[5] N Carolina State Univ, Dept Genet, Raleigh, NC 27695 USA

[6] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA

[7] Natl Jewish Hlth, Denver, CO 80206 USA

[8] Oak Ridge Natl Lab, Oak Ridge, TN 37849 USA

[9] Univ N Carolina, Dept Comp Sci, Chapel Hill, NC 27599 USA

[10] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA

[11] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England

[12] Tel Aviv Univ, Dept Human Microbiol, IL-69978 Tel Aviv, Israel

来源：

GENOME RESEARCH | 2011年 / 21卷 / 08期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

INBRED MOUSE STRAINS; SYSTEMS GENETICS; LABORATORY MOUSE; MICE; ASSOCIATION; RESOURCE; LOCUS; MAP; POPULATIONS; DISSECTION;

D O I：

10.1101/gr.111310.110

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：

The Collaborative Cross (CC) is a mouse recombinant inbred strain panel that is being developed as a resource for mammalian systems genetics. Here we describe an experiment that uses partially inbred CC lines to evaluate the genetic properties and utility of this emerging resource. Genome-wide analysis of the incipient strains reveals high genetic diversity, balanced allele frequencies, and dense, evenly distributed recombination sites-all ideal qualities for a systems genetics resource. We map discrete, complex, and biomolecular traits and contrast two quantitative trait locus (QTL) mapping approaches. Analysis based on inferred haplotypes improves power, reduces false discovery, and provides information to identify and prioritize candidate genes that is unique to multifounder crosses like the CC. The number of expression QTLs discovered here exceeds all previous efforts at eQTL mapping in mice, and we map local eQTL at 1-Mb resolution. We demonstrate that the genetic diversity of the CC, which derives from random mixing of eight founder strains, results in high phenotypic diversity and enhances our ability to map causative loci underlying complex disease-related traits.

引用

页码：1213 / 1222

页数：10

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