Animal DNA offers insights into human health

Learning about how genes malfunction in cats and dogs not only improves their health; it also advances human medicine.

Cats, dogs and humans share pretty much the same genes, says Leslie Lyons, a professor of genetics at UC Davis School of Veterinary Medicine. “Each time we figure out how those genes work in a particular organism, the more we understand about how they work in a human,” she says.

Yet it’s much more difficult to discover the genetic cause of disease in humans than in a purebred dog. People have mated relatively freely over thousands of years, so our DNA tends to come in many varieties. In looking for genetic mutations that differentiate a woman with skin cancer from a woman without it, for example, researchers need to examine as many as a million genetic markers for clues about that kind of malignancy, says Noriko Tonomura, a research assistant professor at the Cummings School.

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Within a line of purebred dogs, however, “large chunks of DNA got passed from one generation to another without interruption,” Tonomura says, essentially mowing the haystack of one million genetic markers in humans down to about 170,000 in one canine breed.

To conduct a genetic study of most canine diseases, researchers need two pools of 200 to 300 dogs, one group with the disease and one without.

“In humans, you’d need 100 times more participants,” says Tonomura. “If we find the gene culprit in a dog, it can guide us to where to start looking to find its equivalent in human patients.”

At Tufts, the veterinary behaviorist Nicholas Dodman led a team that helped pinpoint the only mutation of a behavior gene identified to date: a canine version of the gene for obsessive-compulsive disorder in humans. Found in Doberman pinschers, the defective gene predisposes affected dogs to obsessively suck or lick their flanks.

In a study published earlier this year in the European Journal of Human Genetics, Pablo Moya, a researcher at the National Institute of Mental Health, reported on two segments of the human gene linked to OCD, one predisposing individuals to a more severe form of OCD and the other linking OCD to Tourette disorder.

An imaging study by former Cummings School behavior resident Niwako Ogata, published this year in the journal Progress in Neuro-Psychopharmacology & Biological Psychiatry, found that Dobermans exhibiting compulsive behavior had structural abnormalities in the brain similar to those seen in humans with OCD.

Dodman and research partners Edward Ginns at the University of Massachusetts Medical School, Elaine Ostrander of the National Institutes of Health and Matt Huentleman at T-Gen are hot on the trail of another defective gene, found in English bull terriers, that may cause a canine version of autism spectrum disorder.

“Some bull terriers chase their tails repetitively,” Dodman says. “But they also can have other odd behaviors, including sometimes explosive aggression. They also do this thing called trancing, where they freeze and just stare—and then snap out of it. It’s like an absence seizure.

“The primary behavioral expression of autism in humans is that a child is slow to develop speech and other social behaviors,” says Dodman. “But if you weren’t able to factor speech into the equation—say, for example, an English speaker observing an autistic

child from China—you would still observe repetitive behaviors like rocking or flapping hands, outbursts and sometimes seizures. Affected bull terriers show many of these behaviors.”

If the researchers’ hypothesis proves true, Dodman says bull terriers will expand our understanding of autism biology and enable the development of human genetic tests for autism, which affects 1 in 50 schoolchildren, according to the Centers for Disease Control and Prevention.