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Dog genome published
Dec. 7,
2005
Courtesy Broad Institute of MIT and Harvard Univesity
and World Science staff
Scientists have published a genome sequence of the dog. The information reveals why dog breeds are so diverse, helps clarify the similarities between dogs and humans, and will help explain the many diseases that afflict both species, researchers say.
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Tasha, the boxer whose DNA was sampled for
the dog genome project. (Courtesy National Institutes of Health)
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The research, from an international team of scientists, appears in the Dec. 8 issue of the research journal
Nature.
“The incredible physical and behavioral diversity of dogs—from Chihuahuas to Great
Danes—is encoded in their genomes,” said senior author Eric Lander of the Massachusetts Institute of Technology, Harvard Medical School and the Whitehead Institute for Biomedical Research in Cambridge, Mass.
“It can uniquely help us understand embryonic development, neurobiology, human disease and the basis of evolution.”
Differences between breeds
The team published the sequence along with a catalog of 2.5 million genetic differences across several dog breeds, consisting of single-letter variations of genetic code.
Many of these differences are lumped in huge “blocks” in the dog genome, the scientists
found. Although some human genetic differences also come in similar blocks, the dog blocks are about 100 times larger, explaining why dogs are so diverse, they said.
But the ultimate cause of the diversity is selective breeding by humans, they added.
Dogs were domesticated from gray wolves as long as 100,000 years ago, the researchers asserted. And breeding over the past few centuries has made modern dog breeds a testament to biological diversity.
Examples include the contrasting body sizes of 6-pound Chihuahuas and 120-pound Great Danes, the hyperactivity of Jack Russell terriers relative to mild-mannered basset hounds, and the herding instincts of Shetland sheepdogs compared with the protective tendencies of dalmatians.
In the genome project, researchers first acquired DNA from a female boxer named Tasha, covering nearly 99% of the dog’s genome. Using this information for reference, they then sampled the genomes of 10 different dog breeds and other related canine species, including the gray wolf and coyote.
By comparing these dogs, they pinpointed some 2.5 million differences among breeds consisting of single-letter variations code called single nucleotide polymorphisms. These served as recognizable signposts that can be used to locate the genetic contributions to physical and behavioral traits, as well as disease.
Finally, the scientists used the map of differences to reconstruct how intense dog breeding has shaped the genome.
The huge blocks of diverging code “should make it much easier to find the genes responsible for differences in body size, behavior and disease,” said Lander. “Such studies will need many fewer markers than for human studies. It should be like hitting the side of a barn.”
Similarities to humans
Dogs not only occupy a special place in human hearts, biologists say they also sit at a key branch point in the evolutionary tree relative to humans. By tracking evolution’s genetic footprints through the dog, human and mouse genomes, the scientists found that humans share more of their ancestral DNA with dogs than with mice, confirming the utility of dog genetics for understanding human disease.
Most importantly, the comparison revealed the regions of the human genome that are most highly preserved across mammals.
Roughly 5% of the human genome has been well preserved by evolution over the past 100 million years and therefore must encode important biological functions, the researchers noted.
They also discovered that the most highly conserved of these sequences are not randomly distributed throughout the genome. Instead, they are crowded around just about 1 percent of the genes.
These genes encode crucial regulatory proteins, molecules that govern development. For instance, they fine-tune the actions of groups of other genes, or to help brain cells develop the proper connections among each other.
The clustering of these key gene sequences “is incredibly interesting,” said Kerstin Lindblad-Toh of the Broad Institute, a co-author of the paper. “It means that a small subset of crucial human genes is under much more elaborate control than we had ever imagined.”
Mapping human disease-related genes in dogs
Breeding programs not only selected for desired traits. As a result of inbreeding, they also gave many dog breeds a higher risk of genetic diseases, including heart disease, cancer, blindness, cataracts, epilepsy, hip dysplasia and deafness.
Ironically, this may turns out to help us, the scientists noted.
With the dog genome sequence and the map of differences, researchers around the world now have the tools to identify these disease genes.
Humans suffer from many of the same illnesses as their four-legged friends and even show similar symptoms, but the genetic underpinnings have proved difficult to trace. “The genetic contributions to many common diseases appear to be easier to uncover in dogs,” said Lindblad-Toh. “If so, it is a significant step forward in understanding the roots of genetic disease in both dogs and humans.”
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