Leveraging variation in genetically diverse mouse strains to study Metabolic Syndrome phenotypes
The Hybrid Mouse Diversity Panel (HMDP) is a systems genetic resource of over one hundred different mouse strains. The genetic variation and subsequent phenotypic variation between strains in the HMDP encompass a spectrum of metabolic phenotypes from weight gain following a high-fat diet to susceptibility to heart and liver disease. My dissertation research focuses on the analysis of genetic and genomic data originating from multiple HMDP studies for Metabolic Syndrome phenotypes. Firstly, I identified DNA methylation patterns associated with diet-induced obesity that were observed across diverse genetic backgrounds. I then asked whether these epigenetic changes were maintained following weight loss in a subset of strains. Secondly, I characterized novel genes for atherosclerosis, Nnmt, Csf1, and Zhx2. Lastly, I used transcriptional approaches with genetically diverse mouse strains to identify susceptibility mechanisms involved in the development of progressive liver disease phenotypes. Taken together, this body of research encompasses genetic, cell-type, gene expression, and epigenetic approaches to investigate mechanisms involved in obesity, heart, and liver disease.