Whole-Genome Sequencing of Inbred Mouse Strains Selected for High and Low Open-Field Activity
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ORIGINAL RESEARCH
Whole‑Genome Sequencing of Inbred Mouse Strains Selected for High and Low Open‑Field Activity Aimee L. Thomas1,8 · Luke M. Evans2,8 · Michaela D. Nelsen1 · Elissa J. Chesler3 · Matthew S. Powers1,8 · Winona C. Booher1,8 · Christopher A. Lowry1,4,5,6 · John C. DeFries7,8 · Marissa A. Ehringer1,5,8 Received: 23 March 2020 / Accepted: 21 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract We conducted whole-genome sequencing of four inbred mouse strains initially selected for high (H1, H2) or low (L1, L2) open-field activity (OFA), and then examined strain distribution patterns for all DNA variants that differed between their BALB/cJ and C57BL/6J parental strains. Next, we assessed genome-wide sharing (3,678,826 variants) both between and within the High and Low Activity strains. Results suggested that about 10% of these DNA variants may be associated with OFA, and clearly demonstrated its polygenic nature. Finally, we conducted bioinformatic analyses of functional genomics data from mouse, rat, and human to refine previously identified quantitative trait loci (QTL) for anxiety-related measures. This combination of sequence analysis and genomic-data integration facilitated refinement of previously intractable QTL findings, and identified possible genes for functional follow-up studies. Keywords Whole-genome sequencing · Anxiety phenotypes · Quantitative trait loci · High and Low Activity strains · GeneWeaver
Introduction Anxiety disorders are among the most common mental disorders observed in the United States, affecting about 31.3% of all adults at least one time in their lifespan, with 19.1% of United States adults experiencing an anxiety disorder in the last year alone (National Institute of Mental Health 2017). Furthermore, those who are suffering from some type of Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10519-020-10014-y) contains supplementary material, which is available to authorized users. Aimee L. Thomas and Luke M. Evans have contributed equally to this work. * Marissa A. Ehringer [email protected] 1
anxiety disorder are 3–5 times more likely to visit a doctor than those who are not (Anxiety and Depression Association of America 2018), and these disorders are highly comorbid with other diseases (Meier and Deckert 2019). Anxiety disorders are estimated to cost ~ $45 billion annually, representing around 30% of total expenditures for all mental illnesses in the United States (DeVane et al. 2005). There is clear evidence that risk for anxiety disorders is determined by a fine interplay between genetics and environment. Heritability estimates for anxiety disorders range between 30 and 50%, based on epidemiological, twin, and family studies (Shimada-Sugimoto et al. 2015) with small contributions from common familial environments 5
Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA
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Department of Physical Medicine and Rehabilitation and Center for Ne
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