Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Biology

Supervisor

Dr. Kathleen Hill

Abstract

Mouse models lack affordable genomic technologies slowing the identification of candidate variants contributing to complex phenotypes. The Mouse Diversity Genotyping Array (MDGA) is a low cost, high-resolution platform permitting genomic diversity assessment. Using a validated list of >500,000 single nucleotide polymorphisms (SNPs), we applied the first comprehensive analysis of SNP differences to detect genetic distance across 362 Mus musculus samples. Genetic distance measured between distantly and closely related mice correlates with known phylogeny and genealogy. Variation detected between C57BL/6J mice is consistent with previous reports of variants within this strain. Putative genetic variation detected between and within tissues indicates somatic mosaicism. Genotype differences detected within a mouse are a complex mixture of technical errors and biological differences. Detailed reconstruction experiments are therefore required to determine array sensitivity at detecting true biological variants. The MDGA shows promise for analyzing mutation accumulation with development, aging, environmental mutagenesis and diseases such as cancers.


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