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Aug 16, 2012

Going to the Dogs

  • Clues to human diseases—including cancer and epilepsy—are emerging from the genome of man’s best friend, according to a longtime dog genetics researcher.

    In a review article published today in The New England Journal of Medicine, Elaine A. Ostrander, Ph.D., chief of the Cancer Genetics Branch of NIH’s National Human Genome Research Institute, said study of disease in dogs is made easier by the creation over time of distinct and diverse lines through breeds. Most purebred dogs have descended from small, closely related parentage with large litters, which makes recessive diseases common among those within the breed.

    Often, Dr. Ostrander said, distinct breeds of dogs are affected by distinct diseases: Copper storage diseases affect Bedlington terriers; narcolepsy, Doberman pinschers. Inbreeding makes it likelier that underlying causes of disease can be found in a specific gene, which is easier for researchers to find that disease causes embedded within a mix of genes.

    “Dog breeds offer the same advantage of reducing locus heterogeneity that is gained by studying humans from geographically isolated countries such as Finland or Iceland,” Dr. Ostrander said in the article.

    “What we most wish to understand about dog health is the very same thing we wish to know about ourselves. When will we, or they, get sick? How is the illness best treated? And what is the likely outcome?” Dr. Ostrander said. “Each half of a pet–human pair wants to know what to expect from the other end of the leash and how to prolong the relationship.”

    Another factor that aids in the study of human diseases through dogs, Dr. Ostrander said, is the size of canine families. Because they are larger, they are thus amenable to conventional linkage mapping.

    Dr. Ostrander cited several examples of how knowledge of human diseases has increased, or could increase, through the study of gene-influenced disorders in dogs:

    • Underlying genetic causes of epilepsy differ in two dog breeds, miniature wire-haired dachshunds versus Lagotto Romagnolo dogs. Extending the study to other breeds of dogs could expand the list of genes that can be involved in epilepsy, allowing scientists to better understand different ways the disease can emerge in humans, Dr. Ostrander said.
    • Leber’s congenital amaurosis type 2, a progressive retinal atrophy in dogs and people that can result in blindness, was successfully treated in a dog by introducing a functional version of the gene RPE65 through a virus. As a result, humans with the disease can now be successfully treated for the disorder, Dr. Ostrander said.
    • Variations of the gene for the protein folliculin are involved in kidney cancer and skin growths in German shepherds, and can be studied for similarities to Birt-Hogg-Dube syndrome, a rare human disorder affecting the skin and lungs that is characterized by multiple benign skin tumors, particularly on the face, neck, and upper chest.

    “The single, large dog pedigree was collected and genotyped in a fraction of the time it took to collect and characterize the many necessary human pedigrees,” Ostrander said.

    Read Dr. Ostrander’s review article here:  http://www.nejm.org/doi/pdf/10.1056/NEJMra1204453


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