Journal
NATURE GENETICS
Volume 48, Issue 8, Pages 919-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3609
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Funding
- NIH [R01GM097737, P50DA037844, T32DA07255, T32GM07197, R01AR056280, R01AR060234]
- Human Frontiers Science Program
- Howard Hughes Medical Institute
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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.
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