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Genome-wide association for testis weight in the diversity outbred mouse population

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Abstract

Testis weight is a genetically mediated trait associated with reproductive efficiency across numerous species. We sought to evaluate the genetically diverse, highly recombinant Diversity Outbred (DO) mouse population as a tool to identify and map quantitative trait loci (QTLs) associated with testis weight. Testis weights were recorded for 502 male DO mice and the mice were genotyped on the GIGAMuga array at ~ 143,000 SNPs. We performed a genome-wide association analysis and identified one significant and two suggestive QTLs associated with testis weight. Using bioinformatic approaches, we developed a list of candidate genes and identified those with known roles in testicular size and development. Candidates of particular interest include the RNA demethylase gene Alkbh5, the cyclin-dependent kinase inhibitor gene Cdkn2c, the dynein axonemal heavy chain gene Dnah11, the phospholipase D gene Pld6, the trans-acting transcription factor gene Sp4, and the spermatogenesis-associated gene Spata6, each of which has a human ortholog. Our results demonstrate the utility of DO mice in high-resolution genetic mapping of complex traits, enabling us to identify developmentally important genes in adult mice. Understanding how genetic variation in these genes influence testis weight could aid in the understanding of mechanisms of mammalian reproductive function.

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Funding

Funding was provided by National Institute of General Medical Sciences (Grant No. P20-GM-103449).

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Authors and Affiliations

  1. Department of Computer Science, Program in Molecular Biology & Biochemistry, Middlebury College, Middlebury, VT, 05753, USA

    Joshua T. Yuan

  2. The Jackson Laboratory, 610 Main Street, Bar Harbor, ME, 04609, USA

    Daniel M. Gatti, Vivek M. Philip & Elissa J. Chesler

  3. Department of Psychology, Middlebury College, Middlebury, VT, 05753, USA

    Steven Kasparek & Clarissa C. Parker

  4. Program in Neuroscience, Middlebury College, Middlebury, VT, 05753, USA

    Andrew M. Kreuzman, Benjamin Mansky, Kayvon Sharif, Dominik Taterra, Walter M. Taylor, Mary Thomas & Clarissa C. Parker

  5. Department of Biology, Program in Molecular Biology & Biochemistry, Middlebury College, Middlebury, VT, 05753, USA

    Jeremy O. Ward

  6. Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA), US National Institutes of Health (NIH), Bethesda, MD, USA

    Andrew Holmes

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  1. Joshua T. Yuan
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Correspondence to Clarissa C. Parker.

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Yuan, J.T., Gatti, D.M., Philip, V.M. et al. Genome-wide association for testis weight in the diversity outbred mouse population. Mamm Genome 29, 310–324 (2018). https://doi.org/10.1007/s00335-018-9745-8

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  • DOI: https://doi.org/10.1007/s00335-018-9745-8

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