UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

Genome-wide analysis of DNA methylation variance in healthy human subjects Jiang, Ruiwei


DNA methylation is a type of epigenetic modification that modulates gene expression by acting as an intermediate between genes and environment; this in turn could trigger phenotypic changes with widespread implications in both disease and population models. Unlike DNA sequence, which is relatively stable and finite, DNA methylation presents itself differently in different tissues, and it is described as the sum of interactions affecting attachment of methyl groups to DNA mostly as a result of development and aging, with minor influences from stochastic variability, and environmental factors. Most studies involving DNA methylation focus on finding epigenetic changes related to pathogenicity or disease, as a result, there are certain foundational questions that remain unanswered. In order to translate the current knowledge into reliable insights, it is important to answer these questions, then standardize research methods and establish reference epigenomes. Here we begin to address this challenge through two avenues: epigenomic characterization and environmental interaction. To characterize the epigenome, we monitored the peripheral blood mononuclear cell DNA methylation levels from healthy subjects over a circadian day, a month, and under prolonged sample storage. We also investigated tissue specific variability in DNA methylation by comparing matched peripheral blood mononuclear and buccal epithelial cell samples from healthy subjects. Lastly, we analyzed the impact of diesel exhaust on the DNA methylation. We discovered that while overall DNA methylation was stable within a circadian day, certain loci demonstrated significant changes over the course of a month. Prolonged sample storage, on the other hand, had an even larger effect on DNA methylation. When we compared differences across tissues, we found that although both tissues showed extensive probe-wise variability, the specific regions and magnitude of that variability differed strongly between tissues. Lastly, in light of environmental influences, we observed that DNA methylation was sensitive to even short-term exposure to diesel exhaust, and we identified associated CpG sites across the functional genome, as well as in Alu and LINE1 repetitive elements, with most of these exposure sensitive sites demonstrating loss of DNA methylation.

Item Citations and Data


Attribution-NonCommercial-NoDerivs 2.5 Canada