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Nat Genet. 2016 Aug;48(8):919-26. doi: 10.1038/ng.3609. Epub 2016 Jul 4.

Genome-wide association study of behavioral, physiological and gene expression traits in outbred CFW mice.

Author information

1
Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.
2
Department of Psychology, Middlebury College, Middlebury, Vermont, USA.
3
Program in Neuroscience, Middlebury College, Middlebury, Vermont, USA.
4
Natural History Museum of Denmark, Copenhagen University, Copenhagen, Denmark.
5
AncestryDNA, San Francisco, California, USA.
6
Department of Biobehavioral Health, Pennsylvania State University, University Park, Pennsylvania, USA.
7
Center for Musculoskeletal Research, University of Rochester, Rochester, New York, USA.
8
Department of Orthopedics and Rehabilitation, University of Rochester, Rochester, New York, USA.
9
School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.
10
Department of Genetics, Stanford University, Palo Alto, California, USA.
11
Department of Biology, Stanford University, Palo Alto, California, USA.
12
Howard Hughes Medical Institute, Stanford University, Palo Alto, California, USA.
13
Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois, USA.
14
Department of Psychiatry, University of California, San Diego, La Jolla, California, USA.
15
Institute for Genomic Medicine, University of California, San Diego, La Jolla, California, USA.

Abstract

Although mice are the most widely used mammalian model organism, genetic studies have suffered from limited mapping resolution due to extensive linkage disequilibrium (LD) that is characteristic of crosses among inbred strains. Carworth Farms White (CFW) mice are a commercially available outbred mouse population that exhibit rapid LD decay in comparison to other available mouse populations. We performed a genome-wide association study (GWAS) of behavioral, physiological and gene expression phenotypes using 1,200 male CFW mice. We used genotyping by sequencing (GBS) to obtain genotypes at 92,734 SNPs. We also measured gene expression using RNA sequencing in three brain regions. Our study identified numerous behavioral, physiological and expression quantitative trait loci (QTLs). We integrated the behavioral QTL and eQTL results to implicate specific genes, including Azi2 in sensitivity to methamphetamine and Zmynd11 in anxiety-like behavior. The combination of CFW mice, GBS and RNA sequencing constitutes a powerful approach to GWAS in mice.

PMID:
27376237
PMCID:
PMC4963286
DOI:
10.1038/ng.3609
[Indexed for MEDLINE]
Free PMC Article

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