Whole exome sequencing of wild-derived inbred strains of mice improves power to link phenotype and genotype
2017
The
house mouseis a powerful model to dissect the
geneticbasis 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 variationknown 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
geneticstudies 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 variationis expected to contribute to phenotypic
variation, as they include 18,496 nonsynonymous variants and 262
early stopcodons. Simulations demonstrate that the higher density of
genetic variationin the Montpellier strains provides increased power for
quantitative geneticstudies. Inasmuch as the power to connect genotype to phenotype depends on
genetic variation, it is important to incorporate these additional
geneticstrains into future research programs.
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