Final results on Dr. Robert K Wayne’s work investigating DNA methylation and its regulation of gene expression in normal and pathological states.
DNA methylation plays a central role in regulating gene expression in both normal and pathological states, with abnormal patterns of methylation having been observed in cancer. However, methylation remains an unexplored dimension of canine disease. Here, we propose to establish the pattern of normal variation in methylomes (the genome-wide collection of methylated sites) from an array-based analysis across a variety of domestic dog breeds. Differences in methylation found between breed lineages will be complemented by the study of gene expression to understand how methylation regulates levels of expression.
Our preliminary analyses have focused on a proof-of-principle approach, surveying the differences in methylation of the X chromosome between male and female dogs. Our expectation is that females will display increased levels of methylation due to the inactivation through methylation of an X chromosome for dosage compensation. We do indeed observe this result, and thus are confident that we have the statistical resolution to detect differential methylation across autosomes as well. We focus on methylation as an aspect of gene regulation that could complement gene mapping studies traditionally completed for exploring the genotypephenotype link.
We propose that methylation data can potentially be useful in predicting pathways involved in canine disease risk and progression. We will establish a publically available web-based resource to serve as a repository for the dog methylomes. The collection of methylomes we generate will contribute to the growing resources that are available for investigation of morphology, disease etiology, advancing therapeutic approaches, and overall canine health.