00336B: Mapping of the Gene for Malignant Histiocytosis in the Bernese Mountain Dog

Grant Status: Closed

Grant Amount: $145,300
Francis Galibert, PhD; CNRS - University of Rennes
April 1, 2005 - March 31, 2007

Sponsor(s): Rhodesian Ridgeback Club of the United States

Breed(s): Bernese Mountain Dog, Rottweiler, Flat-Coated Retriever, French Bulldog, Golden Retriever
Research Program Area: Oncology
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We are interested in finding the genes that predispose the Bernese Mountain Dog (BMD) to malignant histiocytosis (MH) for three reasons. First, we are interested in improving the health of this increasingly popular breed, which is severely affected by this deadly disease. Finding the underlying disease gene will lead to the development of genetic tests that can ultimately generate improvements in breeding programs. Second, once we know the underlying cause of MH we can begin to work toward targeted therapies that improve both life, quality and duration for affected dogs. Finally, we are interested in the genetics of similar disorders affecting humans. We propose two complementary strategies: 1) Family based linkage analysis to track the disease gene in a large BMD family affected with MH; and 2) An association-based linkage study encompassing a minimum of 119 affected and at least 100 unaffected control dogs. Both approaches can be expected to highlight regions of the genome where a gene of interest may lie. In summary, these approaches will allow us to eliminate false positive results, increase statistical power for fine linkage mapping, and provide a large resource for mutation screening.


Hedan, B., Thomas, R., Motsinger-Reif, A., Abadie, J., Andre, C., Cullen, J., & Breen, M. (2011). Molecular cytogenetic characterization of canine histiocytic sarcoma: A spontaneous model for human histiocytic cancer identifies deletion of tumor suppressor genes and highlights influence of genetic background on tumor behavior. BMC Cancer, 11(1). https://doi.org/10.1186/1471-2407-11-201
Shearin, A. L., Hedan, B., Cadieu, E., Erich, S. A., Schmidt, E. V., Faden, D. L., … Ostrander, E. A. (2012). The MTAP-CDKN2A Locus Confers Susceptibility to a Naturally Occurring Canine Cancer. Cancer Epidemiology Biomarkers & Prevention, 21(7), 1019–1027. https://doi.org/10.1158/1055-9965.EPI-12-0190-T

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