Whole Exome Sequencing of Wild-Derived Inbred Strains of Mice Improves Power to Link Phenotype and Genotype

Authors

• Peter L. Chang, Vanguard University of Southern California
• Emily Kopania, University of Southern California, University of Montana
• Sara Keeble, University of Southern California, University of Montana
• Brice A. J. Sarver, University of Montana
• Erica Larson, University of Montana, University of DenverFollow
• Annie Orth, Université de Montpellier
• Khalid Belkhir, Université de Montpellier
• Pierre Boursot, Université de Montpellier
• François Bonhomme, Université de Montpellier
• Jeffrey M. Good, University of Montana
• Matthew D. Dean, University of Southern California

Publication Date

8-17-2017

Document Type

Article

Organizational Units

College of Natural Science and Mathematics, Biological Sciences

Keywords

Phenotypic variation, Strains, Wild progenitors, House mouse, Inbred, Exome

Abstract

The house mouse is a powerful model to dissect the genetic basis of phenotypic variation, and serves as a model to study human diseases. Despite a wealth of discoveries, most classical laboratory strains have captured only a small fraction of genetic variation known to segregate in their wild progenitors, and existing strains are often related to each other in complex ways. Inbred strains of mice independently derived from natural populations have the potential to increase power in genetic studies with the addition of novel genetic variation. Here, we perform exome-enrichment and high-throughput sequencing (~8× coverage) of 26 wild-derived strains known in the mouse research community as the “Montpellier strains.” We identified 1.46 million SNPs in our dataset, approximately 19% of which have not been detected from other inbred strains. This novel genetic variation is expected to contribute to phenotypic variation, as they include 18,496 nonsynonymous variants and 262 early stop codons. Simulations demonstrate that the higher density of genetic variation in the Montpellier strains provides increased power for quantitative genetic studies. Inasmuch as the power to connect genotype to phenotype depends on genetic variation, it is important to incorporate these additional genetic strains into future research programs.

Copyright Date

8-17-2017

Copyright Statement / License for Reuse

All Rights Reserved.

Rights Holder

Springer Science+Business Media, LLC

Provenance

Received from author

Language

English (eng)

Extent

10 pgs

Publication Statement

Copyright is held by Springer Science+Business Media, LLC. User is responsible for all copyright compliance.

Publication Title

Mammalian Genome

Volume

28

Issue

9

First Page

416

Last Page

425

ISSN

1432-1777

Recommended Citation

Chang, P. L., Kopania, E., Keeble, S., Sarver, B. A. J., Larson, E., Orth, A., ..., & Dean, M. D. (2017). Whole exome sequencing of wild-derived inbred strains of mice improves power to link phenotype and genotype. Mammalian Genome, 28(9), 416–425. DOI: 10.1007/s00335-017-9704-9

DOI Link

https://doi.org/10.1007/s00335-017-9704-9