Life Sciences Commons^™

Mouse Genotyping Array-Based Analysis Of Variation At Single Nucleotide Polymorphic Loci In The Context Of Macro- And Micro-Environments, Freda Qi

Electronic Thesis and Dissertation Repository

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 …

Characterization Of Genomic Copy Number Variation In Mus Musculus Associated With The Germline Of Inbred And Wild Mouse Populations, Normal Development, And Cancer, Maja Milojevic

Electronic Thesis and Dissertation Repository

Mus musculus is a human commensal species and an important model of human development and disease with a need for approaches to determine the contribution of copy number variants (CNVs) to genetic variation in laboratory and wild mice, and arising with normal mouse development and disease. Here, the Mouse Diversity Genotyping array (MDGA)-approach to CNV detection is developed to characterize CNV differences between laboratory and wild mice, between multiple normal tissues of the same mouse, and between primary mammary gland tumours and metastatic lung tissue.

A CNV detection pipeline was used in conjunction with evaluated probe sets, targeting 925,378 loci …

A Bioinformatics Analysis Of Contributors To False Discovery For A Mouse Genotyping Array, Nisha Patel

Electronic Thesis and Dissertation Repository

Microarray experiments employing massively-parallel hybridization are valuable for the study of genetic variation, however, errors during hybridization and limitations of single-species design must be considered for use within and across species. The Mouse Diversity Genotyping Array (MDGA) is a low cost, high-resolution microarray with probes that bind to target DNA for variant detection. Errors associated with probe design and incomplete protein removal from target DNA lead to false discovery and thus necessitate examination of probe suitability and target DNA availability. Bioinformatics methods were used to carry out confirmation of probe annotations, assessment of DNA accessibility for hybridization to probes, and …

Somatic Copy Number Mosaicism Contributes To Genomic Diversity In Mus Musculus, Andrea E. Wishart

Electronic Thesis and Dissertation Repository

Copy number variants (CNVs) are a source of genomic variation associated with altered phenotypes. Somatic copy number mosaicism results when different populations of cells in an individual differ due to de novo copy number changes (CNCs). Tissue-specific patterns of CNCs resulting in mosaicism have yet to be characterized in the mouse, an organism frequently used to model human diseases. Here, DNA was sampled from spleen, liver, and cerebellum of eight highly related mice selected from a familial unit. CNVs and CNCs were detected using the Mouse Diversity Genotyping Array with three computational methods (ConsecN, Partek, and PennCNV). Tissue-specific patterns of …

Array-Based Genomic Diversity Measures Portray Mus Musculus Phylogenetic And Genealogical Relationships, And Detect Genetic Variation Among C57bl/6j Mice And Between Tissues Of The Same Mouse, Susan T. Eitutis

Electronic Thesis and Dissertation Repository

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 …