01822: Beyond the Genome: The Intersection of Genes and the Environment in Canine Cancer

Grant Status: Closed

Grant Amount: $29,923
Robert K Wayne, PhD; University of California, Los Angeles
January 1, 2013 - December 31, 2014

Sponsor(s): American Maltese Association, Chihuahua Club of America, Miniature Pinscher Club of America, Inc., Pug Dog Club of America, Inc., Schooley's Mountain Kennel Club, Yorkshire Terrier Club of America, Yorkshire Terrier Club of America Foundation, Inc.

Breed(s): Cavalier King Charles Spaniel, Bloodhound, Whippet, American Eskimo Dog, Airedale Terrier, Irish Setter, Scottish Terrier, Briard, Kerry Blue Terrier, Cocker Spaniel, Tibetan Spaniel, Gordon Setter, Golden Retriever
Research Program Area: Oncology
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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

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