Grant Amount: $70,000

Dr. Elaine Ostrander, PhD, National Human Genome Research Institute

April 1, 2007 - March 31, 2009

Breed(s): Scottish Terrier, West Highland White Terrier

Disease(s): Transitional Cell Carcinoma

Project Summary

We have successfully identified two loci associated with the development of TCC in the three most highly affected dog breeds in the United States. The first locus, which appears to be most highly associated with the disease in STs, has been reduced through fine mapping to two regions comprised of approximately four genes, all of which are fine candidates for enhanced tumor development and progression. We are currently sequencing the genes and searching for the causative mutations. The second locus, which was identified in WHWTs and SSD, may contain a mutation that is fixed or carried at a very high frequency in STs, explaining their increased risk of developing the disease. Studies from human bladder cancer suggest that these two loci may be interacting to create a more aggressive form of bladder cancer in dogs carrying both.

Publication(s)

Ostrander E.A. and Parker H.G. (2007). Human genetics and the canine system in: Human Genetics: Principals and Approaches 4th Edition, Eds: F. Vogel, A. Motulsky, S, Antonarakis and M. Speicher. Springer Publishing, (In Press). Mosher, D.S., Spady, T.C., Ostrander E.A. (2007). Every dog has its day: An overview of the recent advances in canine genetics. In: Genome Mapping in Animals, Eds: C. Kole & Noelle E. Cockett, Springer-Verlag, Berlin, Heidelberg, New York, Tokyo, (In Press). Wayne, R.K., Ostrander E.A. (2007). Lessons learned from the dog genome. Trends In Genetics 23(11):557-67. Cadieu E., Ostrander E.A. (2007). Canine genetics offers new mechanisms for the study of human cancer Cancer Epidemiol Biomarkers Prev. 16(11):2181-3. Quignon P., Herbin L., Cadieu E., Kirkness E.F., H�dan B., Mosher D., Galibert F., Andr� C., Ostrander E.A., Hitte C., (2007). Canine population structure: Assessment and impact of intra-breed stratification on SNP-based association studies. PLOS One. December 19, 2(12): e1324. PMC2129117. Fleischer S., Sharkey, M., Mealey K., Ostrander E.A., Martinez M. (2008). Pharmacogenetic and metabolic differences between dog breeds: Their impact on canine medicine and the use of the dog as a preclinical animal model. The AAPS Journal 10(1): 110-9. Jones, P., Chase, K., Martin, A., Ostrander E.A. Lark, K.G. (2008). SNP-Based association mapping of dog stereotypes. Genetics 179: 1033-44. Lindblad-Toh, K. and Ostrander E.A., The Dog. In "Genetic Variation, a Laboratory Manual," M. P. Weiner, S. B. Gabriel, and J. C. Stephens (eds.). Cold Spring Harbor Laboratory Press, Woodbury, N.Y. 11797 (2008), 700 pgs. Pp. 395-407. Dhawan D, Ramos-Vara JA, Stewart JC, Zheng R, Knapp DW. (2008). Canine invasive transitional cell carcinoma cell lines; In vitro tools to complement a relevant animal model of invasive urinary bladder cancer. Urolog Oncol. Epub jun16.