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

Clarissa C. Parker, Shyam Gopalakrishnan, Peter Carbonetto, Natalia M. Gonzales, Emily Leung, Yeonhee J. Park, Emmanuel Aryee, Joe Davis, David A. Blizard, Cheryl L. Ackert-Bicknell, Arimantas Lionikas, Jonathan K. Pritchard, Abraham A. Palmer

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79 Citations (Scopus)
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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.
Original languageEnglish
Pages (from-to)919-926
Number of pages8
JournalNature Genetics
Volume48
Issue number8
Early online date4 Jul 2016
DOIs
Publication statusPublished - 31 Aug 2016

Bibliographical note

The authors wish to acknowledge technical assistance from: D. Godfrey, S. Lionikaite, V. Lionikaite, A.S. Lionikiene and J. Zekos as well as technical and intellectual input from M. Abney, J. Borevitz, K. Broman, N. Cai, R. Cheng, N. Cox, R. Davies, J. Flint, L. Goodstadt, P. Grabowski, B. Harr, E. Leffler, R. Mott, J. Nicod, J. Novembre, A. Price, M. Stephens, D. Weeks and X. Zhou. This project was funded by NIH R01GM097737 and P50DA037844 (A.A.P.), NIH T32DA07255 (C.C.P.), NIH T32GM07197 (N.M.G.), NIH R01AR056280 (D.A.B.), NIH R01AR060234 (C.L.A.-B.), the Fellowship from the Human Frontiers Science Program (P.C.) and the Howard Hughes Medical Institute (J.K.P.).

Keywords

  • DNA sequencing
  • gene expression
  • genome-wide association studies
  • RNA sequencing

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