Profiling Genomic Diversity in a New Wild Mouse Strain Resource

Document Type

Article

Publication Date

Summer 2021

JAX Location

In: Student Reports, Summer 2021, The Jackson Laboratory

Abstract

Currently, most biomedical research is conducted on classical inbred mouse strains. Classical inbred mouse strains are a very narrow representation of the genetic diversity that exists across mice. Since mouse strains are used as a model for diverse human populations, current inbred strain panels may fail to model the full breadth of human diversity, limiting the implications of biomedical research findings to only a subset of human individuals. This project used Illumina short read whole genome sequencing data processed with established bioinformatic tools (Fastp, BWA, GATK, and snpEff) to characterize the genotypic diversity of these a new inbred mouse strain resource established from a cohort of wild-caught mice from across the Americas. We hypothesized that these strains would capture a wide range of naturally existing mouse diversity, setting the stage for novel discoveries and broadening the impact of research outcomes to a wider range of human individuals. The specific goal of this project was to characterize genotypic and phenotypic diversity in these new inbred mouse strain lines. The findings of this project showed that the genomes of these new inbred strains deviated significantly from the reference genome and other classical inbred strains. Notably, our wild-derived inbred mouse strains harbored a high number of missense mutations and highly deleterious mutations that are not observed in classical inbred mouse strains. Phenotypically, we found that mice from these strains exhibit significant differences in body mass and body fat as compared with both C57BL/6J control mice and each other. Intriguingly, our mice follow the principle of Bergmann’s rule, with mice sampled from more equatorial regions having lower body size. In summary, we have performed an initial genomic and phenotypic characterization of a new wild-derived inbred mouse strain resource We show that these strains harbor a significant number of novel variants that are not captured in existing panels of classical inbred strains, many of which could be useful in the context of disease-modeling and complex trait genetics.

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