Scientists Start Deciphering Dog Genome

Maryann Mott
for National Geographic News
December 10, 2002
Man's best friend may soon have its genome deciphered.

The National Human Genome Research Institute (NHGRI) in Bethesda, Maryland, recently added the dog to its high priority list of organisms to be sequenced once computer capacity becomes available. Canines join a growing group of high priority animals that includes the chimpanzee, chicken, and honeybee.

By comparing the genomes of different organisms, researchers can better understand the structure and function of the human genome.

"Dogs are very good biomedical models if you want to understand human disease," said Kerstin Lindblad-Toh, a geneticist and senior program manager of the mouse genome project at the Whitehead Institute in Cambridge, Massachusetts.

"You can use all the understanding you have of disease in dogs to understand human disease, and vice versa, because the genes are so similar in the two genomes," she said.

The top ten diseases in purebreds include several that are major health concerns to humans, including cancer, epilepsy, retinal disease, cataracts, and heart disease.

First Completed Sequence

The Whitehead Institute, which spearheaded the international effort to map and sequence human and mouse genomes, also wants to take on the job of sequencing the dog, said Lindblad-Toh. An official decision by NHGRI has not yet been made on which institution will get the project or when it will begin. NHGRI financially supports large-scale sequencing at Whitehead as well as two other institutions—the Genome Sequencing Center at Washington University School of Medicine in St. Louis, Missouri, and the Human Genome Sequencing Center at Baylor College of Medicine in Houston, Texas.

A partial sequence of a standard poodle was completed last year by the Institute for Genomic Research in Rockville, Maryland.

A committee of researchers and veterinarians in the United States and Europe will decide which breed to sequence. Candidates include the Ibizan Hound, Pharoah Hound, Samoyed, Saluki, and Maltese. These breeds are somewhat rare and have small breeding populations. There is not a lot of genetic diversity in these breeds, making sequencing easier, say researchers.

All that will be needed from the dog is a blood sample.

After one breed has been sequenced, a single nucleotide polymorphisms map, or SNP map, will be created for 10 others, including the mastiff, bloodhound, greyhound, and Pomeranian. An SNP map shows genetic variations and is laid over the completed sequence. From this, researchers can infer what the genome of another breed looks like without having to spend the time to sequence it, Lindblad-Toh said.

Once the project is given the green light it will take one to two years to complete. Automation and experience gained deciphering the human and mouse genomes will make this and other sequencing efforts go faster and cost less than the early projects, said Lindblad-Toh.

All of the information from the canine genome project will be uploaded to an online public database, she said.

Eliminating Blindness

Access to that information would help Gregory Acland, a veterinarian and senior research associate at Cornell University. For several years he has worked on locating genes that cause retinal diseases in dogs. He and his colleagues developed a test that detects carriers of progressive retinal atrophy (PRA), an inherited disease that causes blindness. The test, when combined with controlled breeding practices eliminated PRA over in the Portuguese Water Dog and several other breeds, Acland said.

Despite advances, there is still a lot more work that needs to be done, continued Acland. The gene that causes PRA has not been identified in about 80 different breeds. A sequenced genome would speed up his research. It could also help researchers determine which gene causes a blinding disorder similar to PRA that exists in humans, called retinitis pigmentosa.

As the tools for identifying diseased genes becomes more sophisticated the techniques can be applied to more complex disorders in canines such as hip dysplasia, epilepsy, cancer, and behavioral problems, like compulsive disorders.

But, he adds: "To tackle those, particularly in real world pedigrees, we need the tools that come out of the canine genome sequencing effort that's just starting."

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