Researchers Publish Dog Genome Sequence

An international team, led by researchers at the Broad Institute of MIT and Harvard, has announced the publication of the genome sequence of the dog.

In the Dec. 8 issue of the journal "Nature", the researchers present a detailed analysis of the dog genome and describe how the data offer the potential for improving the health of man and man's best friend.

"When compared with the genomes of human and other important organisms, the dog genome provides a powerful tool for identifying genetic factors that contribute to human health and disease," said Francis S. Collins, M.D., Ph.D., director of the National Human Genome Research Institute (NHGRI), which supported the research.

"This milestone is especially gratifying because it will also directly benefit veterinary researchers' efforts to better understand and treat diseases afflicting our loyal canine companions."

Two years ago, Kerstin Lindblad-Toh, Ph.D., co-director of the genome sequencing and analysis program at the Broad Institute, and her colleagues embarked on a two-part project to assemble a complete map of the dog genome.

In the first phase, they acquired high-quality DNA sequence covering nearly 99 percent of the dog genome, from a female boxer named Tasha.

The boxer was chosen as a representative of the average purebred dog to produce what has become a reference sequence for the dog genome community.

Using the sequence information as a genetic "compass," they navigated the genomes of 10 different dog breeds and other related canine species, including the gray wolf and coyote.

In this sampling, they pinpointed tiny spots of genetic variation, called single nucleotide polymorphisms, which serve as recognizable signposts that can be used to locate the causes of genetic disease.

"Of the more than 5,500 mammals living today, dogs are arguably the most remarkable," said senior author Eric Lander.

"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."

Humans domesticated the dog, "Canis familiaris", from gray wolves as long as 100,000 years ago. As a result of selective breeding over the past few centuries, modern dog breeds present a model of diversity.

Elaine A. Ostrander, Ph.D., chief of NHGRI's Cancer Genetics Branch, co-authored the "Nature" paper, along with postdoctoral research fellows, Heidi G. Parker and Nate B. Sutter.

"The leading causes of death in dogs are a variety of cancers, and many of them are very similar biologically to human cancers," said Dr. Ostrander.

"Using the dog genome sequence in combination with the human genome sequence will help researchers to narrow their search for many more of the genetic contributors underlying cancer and other major diseases."

Other interesting observations emerged from this cross-genome analysis. For example, the research group found that while different breeds show amazing physical diversity, they often share large segments of their DNA, likely reflecting their recent shared origin.

As a result, genetic tools being developed at the Broad Institute and NHGRI for any one breed of dog are likely to be useful in genetic experiments in nearly any breed.

The international team of researchers also identified roughly 2.5 million single nucleotide polymorphisms sprinkled throughout the dog genome.

SNPs are variations in the DNA code, some of which contribute to diseases or the overall health of a dog.

SNPs also can be used to create a set of coordinates with which to survey genetic changes, both within and across dog breeds.

These efforts revealed that individual breeds have maintained a large amount of genetic variability, despite their long history of restrictive breeding.

"We deeply appreciate the generous cooperation of individual dog owners and breeders, breed clubs and veterinary schools in providing blood samples for genetic analysis and disease gene mapping," said Dr. Lindblad-Toh, who is the paper's first author. "Without their interest and help we could not be doing this work."