Genetic analysis of complex traits in the emerging Collaborative Cross.

Document Type

Article

Publication Date

8-2011

Keywords

Animals, Crosses, Genetic, Female, Gene Expression, Genetic Association Studies, Genome, Haplotypes, Male, Mice, Phenotype, Quantitative Trait Loci

JAX Source

Genome Res 2011 Aug; 21(8):1213-1222

PMID

21406540

Volume

21

Issue

8

First Page

1213

Last Page

1222

ISSN

1549-5469

Abstract

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.

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