Research

The study of basic defects involved in genetic diseases has provided great insight into important biochemical pathways. Current positional cloning approaches have greatly increased our capability to discover and understand the role of many loci through the study of genetic diseases. To date, most mammalian genetic studies have been carried out on the human and mouse genomes. However, studies of the genomes of other mammals are also underway. Studying diverse genomes not only has the potential to provide important insight into evolutionary processes, but also provides us with a wealth of diverse genetic problems to study. During the last several years, our group has focused on creating mapping tools for the canine genome. Currently, we have several hundred highly polymorphic markers spanning the canine genome. Purebred dogs provide interesting gene pools where certain genetic traits and diseases are present with significant frequencies. The relatively high frequency of some of these genetic problems in a given breed and the availability of extensive pedigrees make these diseases highly amenable to linkage studies with the polymorphic markers we have developed. In the next several years, we will be investigating the linkage relationship of these markers to both disease genes and each other. Among the diseases under study are canine copper toxicosis, hereditary hearing loss, Von Willebrand's disease, and several degenerative diseases involving the retina. This approach should lead to the isolation of markers which could be used to counsel the breeders and reduce the incidence of the disease in future generations and characterize the defective genes. Another interesting observation that we are investigating further relates to cancer in purebred dogs. The frequency of dogs presenting with cancer varies greatly, ranging from a few to about 30 percent in different breeds. We have recently initiated a study of the genetics of cancer among the breeds showing relatively high frequencies of cancer. It is possible that certain breeds may have predisposing factors, such as mutations in tumor suppressor genes, at a high frequency. After compiling population genetic data on these breeds, we will be in position to know if any known or novel tumor suppressor gene may be conferring susceptibility in these breeds.