01822: Beyond the Genome: The Intersection of Genes and the Environment in Canine Cancer
Grant Status: Closed
Not all genes are active at all times. DNA methylation (the addition of methyl groups to DNA) is one of several mechanisms that cells use to control gene expression. Abnormal patterns of DNA methylation have been observed in human cancer. However, methylation remains an unexplored dimension of canine disease. This seed grant to Dr. Wayne will allow him to establish the techniques and methodologies necessary to define the pattern of normal variation in methylomes (the genome-wide collection of methylated sites) from an array-based analysis of 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. Upon completion of this study, Dr. Wayne's laboratory will have proof-of-principle for evaluation of the canine methylome. Ultimately, he intends to establish a public web-based resource to serve as a repository for the dog methylomes. The collection of methylomes they generate will contribute to the growing resources that are available for investigation of disease etiology as well as advancing therapeutic approaches. These data will provide a new resource for understanding how gene regulation through methylation affects phenotype, disease and overall canine health.
Janowitz Koch, I., Clark, M. M., Thompson, M. J., Deere-Machemer, K. A., Wang, J., Duarte, L., … vonHoldt, B. M. (2016). The concerted impact of domestication and transposon insertions on methylation patterns between dogs and grey wolves. Molecular Ecology, 25(8), 1838–1855. https://doi.org/10.1111/mec.13480
Mariano, R., & vonHoldt, B. (2016). The canine X chromosome is a sink for canine endogenous retrovirus transposition. Gene Reports, 4, 169–176. https://doi.org/10.1016/j.genrep.2016.05.003
Thompson, M. J., vonHoldt, B., Horvath, S., & Pellegrini, M. (2017). An epigenetic aging clock for dogs and wolves. Aging, 9(3), 1055–1068. https://doi.org/10.18632/aging.101211
Help Future Generations of Dogs
Participate in canine health research by providing samples or by enrolling in a clinical trial. Samples are needed from healthy dogs and dogs affected by specific diseases.