Whole-Genome Sequencing of Inbred Mouse Strains Selected for High and Low Open-Field Activity

Aimee L Thomas; Luke M Evans; Michaela D Nelsen; Elissa J Chesler; Matthew S Powers; Winona C Booher; Christopher A Lowry; John C DeFries; Marissa A Ehringer

doi:10.1007/s10519-020-10014-y

Whole-Genome Sequencing of Inbred Mouse Strains Selected for High and Low Open-Field Activity

Behav Genet. 2021 Jan;51(1):68-81. doi: 10.1007/s10519-020-10014-y. Epub 2020 Sep 16.

Authors

Aimee L Thomas^#^{1

2}, Luke M Evans^#^{3

2}, Michaela D Nelsen¹, Elissa J Chesler⁴, Matthew S Powers^{1

2}, Winona C Booher^{1

2}, Christopher A Lowry^{1

5

6

7}, John C DeFries^{8

2}, Marissa A Ehringer^{9

10

11}

Affiliations

¹ Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
² Institute for Behavioral Genetics, University of Colorado Boulder, 447 UCB, Boulder, CO, USA.
³ Department of Ecology and Evolutionary Biology, University of Colorado Boulder, Boulder, CO, USA.
⁴ Jackson Labs, Bar Harbor, ME, USA.
⁵ Center for Microbial Exploration, University of Colorado Boulder, Boulder, CO, USA.
⁶ Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
⁷ Department of Physical Medicine and Rehabilitation and Center for Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁸ Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
⁹ Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA. Marissa.Ehringer@colorado.edu.
¹⁰ Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA. Marissa.Ehringer@colorado.edu.
¹¹ Institute for Behavioral Genetics, University of Colorado Boulder, 447 UCB, Boulder, CO, USA. Marissa.Ehringer@colorado.edu.

^# Contributed equally.

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: Anxiety phenotypes; GeneWeaver; High and Low Activity strains; Quantitative trait loci; Whole-genome sequencing.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Anxiety / genetics*
Anxiety Disorders / genetics
Chromosome Mapping / methods
Computational Biology / methods
Disease Models, Animal
Exome Sequencing / methods
Genomics / methods
Genotype
Humans
Mice
Mice, Inbred BALB C / genetics
Mice, Inbred C57BL / genetics
Mice, Inbred Strains / genetics*
Open Field Test / physiology*
Phenotype
Polymorphism, Single Nucleotide / genetics
Quantitative Trait Loci / genetics
Rats

Abstract

Publication types

MeSH terms

Grants and funding