00935B: Positional Cloning of Two Genes for Malignant Histiocytosis (MH) in the Bernese Mountain Dog
Grant Status: Closed
Project SummaryWhile rare in the general canine population, histiocytic cancers occur at a high incidence in several breeds, most notably Bernese mountain dogs (BMD) and flat-coated retrievers (FCR). Primarily through the generosity of grants funded by the AKC Canine Health Foundation, the investigators have identified two genomic regions that associate with histiocytic cancer in the BMD and two regions similarly associated in the FCR. This represents a major step forward in the understanding of the disease and is likely to shed light on similar conditions in humans as well. This research program is continuing with the support of Grant 1410A&B. Critical to the next stage of the study will be the researchers' efforts to pinpoint the exact mutations that cause the disease in both breeds, and to get that work published as quickly as possible. The investigators hope that from their work a clearer understanding of the gene families involved, as well as the underlying pathology, will evolve. In addition, they hope to better understand the tissue specificity of the genes involved. That is, why do dogs with specific mutations get histocytic cancers as opposed to other kinds of cancer? The investigators also plan to continue their tissue expression studies and identify genes that are up regulated or down regulated in tumor tissues. Those experiments, should lead to improved diagnostics and treatment in affected breeds. Finally, they hope that genetic tests will eventually develop from the foundations laid by this work so that healthier, more long-lived dogs can be bred. In the next and final stages of the work the investigators sincerely hope that the breed clubs will remain viable and important partners, both in the United States and Europe. This work truly could not make progress without you. The investigators will continue to accept samples from affected dogs and ask, as in the past, that you provide detailed pedigrees and clinical information with samples. They believe that this final push will take them across the finish line in terms of understanding how this terrible disease in inherited. The researchers have come so far and made so much progress. Now let's work together to get across the finish line! Thank you!
Publication(s)Abadie, J, Hedan, B, Cadieu, E, De Brito, C, Devauchelle, P, Bourgain, C, Parker, Hg, Vaysse, A, Margaritte-Jeannin, P, Galibert, F, Ostrander, Ea and Andre, C (2009) Epidemiology, Pathology, and Genetics of Histiocytic Sarcoma in the Bernese Mountain Dog Breed. J Hered. 100, S19-27. 10.1093/jhered/esp039 http://jhered.oxfordjournals.org/cgi/content/abstract/100/suppl_1/S19 Shearin, Al and Ostrander, Ea (2010) Leading the way: canine models of genomics and disease. Disease Models & Mechanisms. 3, 27-34. 10.1242/dmm.004358 http://dmm.biologists.org/content/3/1-2/27.abstract Shearin, Al and Ostrander, Ea (2010) Canine Morphology: Hunting for Genes and Tracking Mutations. PLoS Biol. 8, e1000310. http://dx.doi.org/10.1371%2Fjournal.pbio.1000310
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