Dog Genome Successfully Sequenced

An international research team led by scientists at the Broad Institute of MIT and Harvard recently announced the completion of a high-quality genome sequence of the domestic dog, along with a catalog of specific genetic differences across several dog breeds.

Published in the Dec. 8 issue of the scientific journal Nature, the dog research sheds light on both the genetic similarities to humans and the genetic differences between dog breeds. Humans share more of their ancestral DNA with dogs than with mice, confirming the utility of dog genetics for understanding human disease.

Examining data across breeds helps to illuminate the structure of genetic variation among breeds, which can now be used to understand the basis of physical and behavioral differences, as well the genetic underpinnings of diseases common to domestic dogs and their human companions.

“Of the more than 5,500 mammals living today, dogs are arguably the most remarkable,” said senior author Eric Lander, director of the Broad Institute, professor of biology at MIT and systems biology at Harvard Medical School, and a member of the Whitehead Institute for Biomedical Research.

“The incredible physical and behavioral diversity of dogs—from Chihuahuas to Great Danes—is encoded in their genomes. It can uniquely help us understand embryonic development, neurobiology, human disease and the basis of evolution.”

Dogs were domesticated from gray wolves as long as 100,000 years ago, but selective breeding over the past few centuries has made modern dog breeds a testament to biological diversity. More than two years ago, researchers embarked on a two-part project to assemble a complete map of the dog genome.

First, they acquired high-quality DNA sequence from a female boxer named “Tasha,” covering nearly 99 percent of the dog’s genome. Using this information as a genetic ‘compass,’ 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 about 2.5 million individual genetic differences among breeds, called SNPs (single nucleotide polymorphisms), which serve 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 SNP map to reconstruct how intense dog breeding has shaped the genome. They discovered that selective breeding carried large genomic regions of several million bases of DNA into breeds, creating ‘haplotype blocks’ that are about 100 times larger than seen in the human population

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Sequencing of the dog genome began in June 2003, funded in large part by the National Human Genome Research Institute (NHGRI). The Broad Institute is part of NHGRI’s Large-Scale Sequencing Research Network. NHGRI is one of 27 institutes and centers at the National Institutes of Health, an agency of the Department of Health and Human Services. All of the data can be accessed through public databases.

The Broad Institute’s 60 core and associate researchers target fundamental issues, including chemical biology, genome sequencing and analysis, medical and population genetics, cancer, and infectious disease.

One of its primary benefactors, the Broad Foundation, recently announced it would double the initial donation from $100 million to an unprecedented $200 million. This is the largest gift of its kind to two universities for a joint research endeavor.

Commenting on the work fostered by the atmosphere at the Institute, benefactor Eli Broad said, “This unprecedented partnership between MIT and Harvard University, together with the Harvard Hospitals and the Whitehead Institute, has resulted in a research community that is tackling some of the most important questions in biomedicine.”

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