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Mouse Genotyping Array-Based Analysis of Variation at Single Nucleotide Polymorphic Loci in the Context of Macro- and Micro-environments

Freda Qi

Abstract

Comparing genetic variation between populations can provide insight into selective pressures in the environment. The Mouse Diversity Genotyping Array (MDGA) is a low-cost, high-throughput tool developed to capture and analyze variation at single nucleotide polymorphic (SNP) loci in inbred mouse strains. However, its ability to assess genetic variation in non-inbred mice and associate SNPs with the environment has not been extensively studied. First, SNPs between laboratory inbred and wild-caught mice were compared. No SNPs were associated with either macroenvironment. Instead, SNPs reflected genealogy and inbreeding strategies, consistent with the MDGA’s intended use. Second, mutations at SNP loci were compared between a mouse model of breast cancer metastasis with and without Receptor for Hyaluronan-Mediated Motility (RHAMM). Genetic homogeneity observed in the lung microenvironment without RHAMM is consistent with strong purifying selection. In conclusion, the MDGA is effective for associating SNPs with the environment only when selective pressures exceed genetic background effects.