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December 08, 2005

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Dog genome latest DNA to be fully sequenced

Major advance in genomics

By Alvin Powell
Harvard News Office

Tasha the boxer
Tasha is the first dog to have her DNA sequenced. The dog genome has been partially decoded in the past, but the Broad's effort has produced a genetic map of the dog that researchers say is 99 percent complete. (Photo courtesy of NIH)
Scientists at the Broad Institute of Harvard and MIT have sequenced the domestic dog's DNA, thanks to the blood of a boxer named Tasha. Now they hope to follow Tasha's genetic code to a new understanding of shared diseases (such as cancer) and the genetic roots of the differences between man and beast.

The unique variation among dog breeds, each of which has specific appearances, behavioral traits, and tendencies toward disease, make the dog an ideal animal for genetic analysis, researchers said.

The work entailed determining the order of 2.4 billion chemical bases that make up dog DNA, the long molecule that contains the dog's genetic blueprint. The dog genome has been partially decoded in the past, but the Broad's effort has produced a genetic map of the dog that researchers say is 99 percent complete.

Knowing the makeup of a dog's DNA is an enormous aid to researchers trying to figure out where genes responsible for specific traits or defects are located. Kerstin Lindblad-Toh, co-director of the Broad's genome sequencing and analysis program, said that knowing the sequence of an animal's DNA allows comparisons with human DNA, improving understanding of both humans and animals.

Broad Institute officials made the announcement Wednesday (Dec. 7) at Boston's Bayside Expo Center the day before the opening of the Bay Colony Cluster Dog Show, which will bring thousands of dogs and their owners to the arena.

Broad Institute Director Eric Lander, professor of systems biology at Harvard Medical School, called the event "historic" and said that scientists who have been long intrigued by the broad variation among the different dog breeds finally have a tool to really understand it.

"We're finally in a position to unravel the many secrets of the dog," Lander said. "Dogs are prepared to teach us new tricks."

The work, begun in June 2003, involved an international team of scientists led by researchers at the Broad. It was largely funded by the National Human Genome Research Institute and published in the Dec. 8 issue of the journal Nature.

Dogs and humans have shared the same environment through thousands of years of companionship, Lindblad-Toh said, and they get many of the same illnesses and diseases. While the extreme variability in the human genetic code makes it difficult to track the genetic causes of disease in people, Lindblad-Toh said the inbreeding that created today's dog breeds, coupled with the inherited tendencies to specific diseases, may make that task easier in dogs.

Researchers will now be able to compare the genetic codes of similar dogs, one that developed a particular condition and one that didn't, and pick out the places where their genetic codes differ for further study.

"The comparison of genomes provides a very powerful window into the function of our own genome," said Francis Collins, director of the National Human Genome Research Institute.

The ability to compare different animal genomes has already borne fruit, Lindblad-Toh said. An earlier comparison of human and mouse DNA showed a small percentage was highly conserved, remaining largely the same despite the passage of enough time that there should have been an accumulation of random mutations. The analysis of the dog genome showed the same part of the DNA conserved, revealing that it is concentrated in a region of the DNA that contains regulatory proteins involved in development.

Lindblad-Toh said that that is an indication that those genes are involved in basic mammalian development, perhaps the regulation the body plans as an embryo develops.

Early analysis of the dog genome provides a bit of humility for humans as well, researchers said. An earlier comparison of the genes responsible for brain development in mice and humans showed much more rapid change in humans and led scientists to believe that it was a sign of the uniqueness of the human brain. An analysis of the same genes in the dog, however, showed that the dog brain has changed just as much as the human brain.

The work included a comparison of the genome of 10 dog breeds and some wild cousins. Researchers pinpointed 2.5 million differences among breeds that researchers can begin exploring for clues to the vast variations in specific traits.

Lindblad-Toh said researchers are already embarking on a project to investigate dog diseases, with an emphasis on cancers. Elaine Ostrander of the National Human Genome Research Institute said another avenue opened up by the work will explore the link between genetics and dog behavioral traits. Similar work was abandoned years ago, she said, because researchers didn't have the necessary analytical tools.

"This is really an exciting time for human and dog geneticists," Ostrander said.


Related stories:

  • Chimp genome effort shines light on human evolution:
    Broad Institute and Washington University lead the decoding effort

  • HapMap reveals roots of common diseases:
    May improve prediction, prevention, and treatment

  • Variations discovered in human genomes

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