The Molecule of Life

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Apr 01, 2006

It's the greatest scientific puzzle.

Deoxyribonucleic acid (DNA), a.k.a. the molecule of life, harbors an estimated 20,000 to 200,000 canine genes hidden in the DNA across from 38 pairs of chromosomes, all contributing to health and disease. Sleuthing out defects along genes nucleotides, or base pairs, seemingly turns into a numbers game that can add up into the billions.

Dr. Elaine Ostrander, director of Cancer Genetics Branch of the National Human Genome Research Institute of the National Institutes of Health, reports the canine model represents true scientific potential.

The unveiled sequenced canine genome announced last December was heralded as a critically important scientific marker, and it sets the stage for major exploration during the next 10 years. To date, about 2.5 million single nucleotide polymorphisms have been identified. These variants in the DNA code contribute to disease.

So, why the dog? With only 350 varieties (families) and 15,000 years since man began selective breeding, it represents a mere tick on the genetic clock. Each breed offers a unique panel of polymorphisms never encountered in other mammals. About 70 percent of dog DNA is identical. Now consider canine cancer. The presentation of disease in humans is quite similar. This combination and the crossover potential to human medicine makes the purebred dog a genetics researcher's best friend.


Cracking the code
Ostrander remains hopeful that the next 10 years will be rife with discovery of genetic variants that lead to new screening tests and new improved therapies for treating disease from cancers to heart disease.

This crossover potential to human medicine also opens up the coffers to major research cash. In other words, dog stands to benefit a great deal.

"Understanding the genes in dogs is going to be important for anyone interested in pursuing cancer genetics and cancer biology," Ostrander says.

"Dogs offer an opportunity for us to tackle some of the cancers that have been very difficult to understand the genetic makeup nature in humans because canine families are much bigger and because of the breed barrier. In humans, there might be a dozen genes for osteosarcoma just to pull a number out of thin air, but for any one breed, the Rottweiler, Irish Wolfhound or Scottish Deerhound, that number is going to be considerably less because the breed barrier has restricted the number of deleterious genes for any disease," she explains.

"So, there has been a real sense of excitement of people in the field to look at lymphomas, osteosarcomas, melanomas and a variety of different types of cancers that are of interest for human health as well as some of the cancers that aren't such a big deal for human health, like hemangiosarcoma, malignant histiocytosis."

Under investigation

Ostrander's Bethesda, Md. laboratory is focused on finding the susceptibility gene for three important canine cancers: malignant histiocytosis in Bernese Mountain Dogs and Flat-coated Retrievers; bladder cancer working in conjunction with Purdue University and University of Minnesota and lymphoma, especially T-cell lymphomas.

She adds that other laboratories around the country are focused on melanoma, osteosarcoma, B-cell lymphomas, hemangiosarcomas and CNS tumors.

"There have been groups coming forward expressing a strong interest for all of the canine cancers," she says. "I think it is an area that is really going to explode in the next few years.

"As we start to unravel the complex genetics of cancer, it is really going to set the stage for how to tackle many of these other diseases."

Hip dysplasia is one such disease that affects an estimated 50 percent of all dogs, especially large breed dogs. "I think the availability of the genome sequence has dramatically changed the rate at which we do our work," she adds.

The worldwide publicity spawned by the decoded canine genome helped generate more collaboration among scientists and sped the ability to pinpoint genes of interest.