Mutational Load in Inbred-Outbred Wild Derived Mouse Trios

Sam G. Bigalke

Document Type

Article

Publication Date

2025

Keywords

JMG

Abstract

Inbred mice offer a genetically standardized and reproducible model for studying human disease, reproduction, and basic biology. However, due to their, often, completely homozygous genomes, many inbred models lack genomic variation present in genetically diverse natural populations, like humans. In contrast, wild-type models and their derivative inbred strains present a means of achieving high genetic diversity in laboratory settings that may have deep clinical relevance. In this study, I am assessing how mutational load changes throughout the inbreeding process, and what implications may arise from this allelic spectrum in laboratory mice models. My project shows that wild-derived inbred strains have a reduced mutational burden as compared to their wild-caught counterparts. This reduction indicates a disproportionate purging of deleterious alleles as compared to other alleles, shifting the allelic effects within the genome.

This could imply that the standard inbred strains used in biomedical research may have limitations when looking a disease relevant allele, due to their deleteriousness limiting their ability to make it into the model. Moreover, this suggests that wild-caught mice may offer a better means of studying the allelic effects found in human populations. Through mapping mutational burden on a genome wide scale, and identifying regions under selective pressures, we may gain insight into how the inbreeding process shaped genetic models in laboratory settings.

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