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NIH funds two Veterinary Medicine clinical research programs

Cornell University's College of Veterinary Medicines clinical research program will receive $1,000,000 in NIH funding over the next four years. The funding will support two initiatives: the DNA Bank and common variable immunodeficiency in horses.

The DNA Bank was established in 2006 to better understand the genetic basis for canine diseases. The bank currently contains nearly 3000 DNA samples collected from pedigreed canines visiting the Cornell University Hospital for Animals for diagnosis and treatment of diseases. Greg Acland, professor of medical genetics, is the principal investigator for the four-year, $900,000 (direct costs) R24 grant from the NIH.

The grant will be used to establish a DNA archive of control and diseased purebred dogs; to genotype diseased and control purebred dogs; and to encourage multi-institutional mapping collaborations and share genotypes with the entire genetics community.

"The secret to the success of an excellent DNA archive is collaboration among a wide group of researchers as well as cooperation among the entire staff, including licensed veterinary technicians, interns, residents and faculty who look after the dogs admitted to the Cornell University Hospital for Animals and who ascertain the diseases the dogs carry, and collect the blood samples from which the DNA of each animal is isolated with owner permission and cooperation," said Rory Todhunter, professor of surgery. "In addition, the dog owners are key to the project's success as they must provide AKC numbers and pedigree information about their dogs."

As such, Acland will partner with faculty across Cornell University including John Schimenti, Todhunter, Nate Sutter, Jason Mezey, Carlos Bustamante and Wei Wang, Manager of the Microarray core facility in the Veterinary College as well as Marta Castelhano who handles the daily operations of the DNA Bank (including phenotypic ascertainment) and Liz Corey, who manages and executes the lab operations at the Colleges Baker Institute for Animal Health.

During the course of the grant, the group plans to map the genetic locus of up to 12 complex genetic traits. With this information, breeders and researchers across the world will have access to information that can help produce the best dogs for specialized tasks, reduce disease risk substantially, and develop novel treatments and interventions sooner.

"Identifying genes underlying complex traits in mammals remains a challenge," said Todhunter. "However, with its genome sequenced and a single nucleotide polymorphism map now available, the dog is ready to contribute to mammalian biology in a bridging role between mouse and man, with less genetic heterogeneity than human populations and yet more naturally occurring disease than the mouse."

Julia Bevilaqua Felippe, the Harry M. Zweig assistant professor in equine health and assistant professor of large animal medicine, received a two-year grant in the amount of $100,000 to study common variable immunodeficiency in horses.

Cornell University diagnosed the first case of the common variable immunodeficiency in horses in 2001. Horses affected by this disease cannot make antibodies because they lack B cells, which are responsible for antibody production. Our data suggests that these cells have an impaired development in the bone marrow but are also lost from the lymphoid tissues with time.

"We have diagnosed this potentially fatal disease in 14 horses," said Bevilaqua Felippe. "It is intriguing because affected horses that have been healthy for years become susceptible to infections, and present recurrent pneumonia and bacterial meningitis because of the lack of antibodies. The difficulty in understanding this disease is that by the time the case is diagnosed, the cells responsible for antibody production B cells are not present."

To counter the absence of the critical cells, Bevilaqua Felippe's research team will use the grant to develop a horse/mouse chimera, and use a SCID mouse to serve as the recipient of horse immune cells. Researchers will monitor how horse B cells develop and respond to immunizations in the mouse.


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