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Man's Best Friend Points the Way in Genetic Research
Date:8/16/2012

By Barbara Bronson Gray
HealthDay Reporter

WEDNESDAY, Aug. 15 (HealthDay News) -- Dogs may soon become man's best friend on a level that goes far beyond companionship and loyalty.

Researchers report that the canine genome, similar in many ways to the human one, is starting to shed light on a wide range of human diseases.

What makes dogs particularly interesting to scientists is their breed structure -- a type of artificial selection -- which creates distinct and diverse lines of animals that range from the muscular German shepherd to the nervous Chihuahua, from the hard-working collie to the perpetually pampered poodle.

According to a review article published Aug. 16 in the New England Journal of Medicine, the fact that most purebred dogs have descended from small, closely related parentage with large litters means recessive diseases are common among them.

To those interested in genetics, that's exciting.

It makes less common recessive diseases (which can't be seen or expressed unless the responsible gene is carried by both parents) more prevalent in these animals. And that opens the window to understanding the genetic underpinnings of a wide range of conditions that humans and dogs share.

"The dog genome is very similar to humans," said review author Elaine Ostrander, chief of the Cancer Genetics Branch of the National Human Genome Research Institute at the U.S. National Institutes of Health. "It's closer to us than the genomes of mice, rats or fruit flies, which are often used in research. Dogs also live side-by-side in our environments with us; they drink the same water, they breathe the same air, they're exposed to the same pesticides and they often even eat some of the same food."

Ostrander said dogs and humans get almost all of the same diseases, including cancer, arthritis, epilepsy, retinal atrophy, autoimmune disorders such as lupus, and psychological problems such as obsessive-compulsive disorder.

There are 400 different breeds, and many are associated with greater risk of getting particular diseases, Ostrander said. "A particular torsion [twisting] of the intestine is the only thing we see in dogs but not in humans."

Cancer is the number one cause of death in dogs, said Dr. Ned Patterson, an associate professor of veterinary medicine and genetics at the University of Minnesota. "Because the mechanism [of the disease] and the therapies are similar, we can really learn a lot about cancer in both directions, even concurrently," he noted.

Chromosome changes observed in several canine cancers are seen in the corresponding cancers in humans. This suggests a shared genetic origin of several cancers that affect both dogs and humans. By focusing on what parts of genes are altered in both species, the number of potential target genes can be reduced to a handful.

Dogs participating in genetic studies typically come to research labs with their caregivers for a brief appointment. They get their blood drawn and have their cheeks swabbed for analysis before returning home, Patterson explained. Currently, there are 87 genetic tests for dogs, primarily used by breeders trying to prevent health issues associated with certain breeds, he added.

Sometimes discoveries related to illnesses in dogs translate to treatments in humans, Patterson explained. "In narcolepsy, we found a new biochemical pathway related to sleep in dogs that may be helpful in humans."

The dog genome sequence was first published in 2005. While most genome-wide studies linking genetic characteristics to diseases or traits have required thousands of samples, such analyses in dogs have successfully been mapped with fewer than 200 dogs, Ostrander said.

Dog breeds provide a clustering of genes not unlike what is seen by studying remote or isolated populations of humans in places like Finland or Iceland. For any complex disease in dogs, a small number of genes and problem alleles (one part of a pair or series of genes that sits in a specific spot on a specific chromosome) will dominate the breed, much as a type of BRCA2 mutation does in Icelandic women with hereditary breast cancer.

Ostrander used the example of epilepsy to explain how dog genetics can help researchers unpack the complexity of the disease in humans, where it's expressed in a wide range of ways. Epilepsy affects 5 percent of dogs and is seen across dozens of breeds. Details of how different genes in various breeds are associated with specific symptoms or types of epilepsy offer clues into the genetic issues that may be associated with the disease in humans, she said.

The dog genome continues to provide new insights into the human condition. "Everything we've learned by studying canine genetics has certainly informed our thinking about human genetics," said Ostrander.

The next big area of research, Ostrander predicted, will be gene-environment interaction. Like a canary in a mine, dog conditions may help alert researchers to genes that are most affected by environmental factors -- everything from pesticides to food dyes and water quality, she explained.

Dr. Laura Kahn, a research scholar in the program on Science and Global Security at the Woodrow Wilson School of Public and International Affairs at Princeton University, said: "There's a tremendous overlap and a lot to be learned to benefit not just animal health, but human health. Our future survival and global sustainability is dependent on this paradigm."

More information

Learn about the Dog Genome Project from the Broad Institute.

SOURCES: Elaine Ostrander, Ph.D., chief, Cancer Genetics Branch, National Human Genome Research Institute, U.S. National Institutes of Health, Bethesda, Md.; Ned Patterson, D.V.M., Ph.D., associate professor, veterinary medicine and genetics, University of Minnesota, Saint Paul; Laura Kahn, M.D., M.P.H., M.P.P., research scholar, Program on Science and Global Security, Woodrow Wilson School of Public and International Affairs, Princeton University, New Jersey; Aug. 16, 2012, New England Journal of Medicine


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