Friday, January 22, 2010

Genome Dog May Shed Light On Human Disease

Scientists have managed to sequence the dog genome, an achievement that could lead to better health for humans and dogs. A team of international researchers have published a detailed analysis in the journal Nature.

"From more than 5,500 mammals living today, dogs are arguably the most extraordinary," said senior author Eric Lander, PhD, director of the Broad Institute of MIT and Harvard. He is a professor of biology at MIT and systems biology at Harvard Medical School, as well as a member of the Whitehead Institute for Biomedical Research.

"The incredible physical and behavioral diversity of dogs from Chihuahuas to Great Danes encoded in their genomes. This unique that can help us understand embryonic development, neurobiology, human disease and the basis of evolution," Dr. Lander notes.

Powerful Tool
"When compared with the human genome 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, MD, PhD, director of the National Human Genome Research Institute, which supports research.

"This milestone is especially satisfying because it will directly benefit the animal researchers' efforts to better understand and treat diseases suffered by our faithful friend the dog," said Dr Collins added.

Human pet dog, Canis familiaris, from gray wolves as long as 100,000 years ago. As a result of selective breeding for several centuries, modern dog presents a model of diversity. From the six-pound Chihuahuas to 120-pound Great Danes, from high-energy Jack Russell Terriers to mild-mannered basset dog, and from Shetland sheepdogs with their herd instinct tends to a pointer to the point, humans have bred dogs for desirable physical characteristics and behavior .

Maintenance practices such as the choice of maintaining the characteristics of one generation in the next, but they also affect many dogs genetic disorders, including heart disease, cancer, blindness, cataracts, epilepsy, hip dysplasia and deafness.

Research group found that while the descendants of different shows differences extraordinary physical, they often share large segments of their DNA, perhaps reflecting their common origin recently. As a result, genetic tools being developed at the Broad Institute and NHGRI for any one type of dog that might be useful in genetic experiments in nearly every breed.

Evolutionary Tree
While dogs occupy a special place in the hearts of men, they also sat on the main branch point, relative to humans, the evolutionary tree. It is known that humans share more of their ancestral DNA with dogs more than a mouse. The availability of the dog genome sequence has allowed researchers to describe a common set of genetic elements represent about 5 percent of the human genome are preferentially preserved among human, dog and mouse.

Not evenly, some of these elements are crowded around just a fraction of the genes in the genome. Future studies of this group could give scientists the critical insight needed to unravel how genomes work.
Elaine A. Ostrander, PhD, head of NHGRI Cancer Genetics Branch, is a co-author of the Nature paper, along with postdoctoral research fellows, Heidi G. Parker and Nate B. Sutter. In addition, Dr. Ostrander was the lead author of the white paper that sets forth the reasons for biomedical dog genome sequence.

Dr. Ostrander's laboratory maps genes responsible for susceptibility to cancer, including breast and prostate cancer in canines and humans.
"The main cause of death in dogs are a variety of cancers, and many of them are very similar to human biological cancer." said Dr. Ostrander. "Using the dog genome sequence in combination with the human genome sequence will help researchers to narrow their search for more genetic contributors underlying cancer and other serious diseases."

Genetic Compass
Efforts to create the genetic tools needed for mapping disease genes in dogs have gained momentum over the last 15 years, and have included a partial survey of the poodle genome. More than two years ago, Kerstin Lindblad Toh, PhD, co director of genome sequencing and analysis program at the Broad Institute, and colleagues began the project two parts to assemble a complete map of the dog genome.

First, they obtain high quality DNA sequence covering nearly 99 percent of the genome of the female boxer dog named Tasha. Boxer was chosen as a representative of the average 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 and other dog species concerned, including gray wolves and coyotes.

The researchers identified approximately 2.5 million single nucleotide polymorphisms, or SNPs, sprinkled throughout the dog genome. SNPs are variations in the DNA code, some of which cause disease or the overall health of dogs.

SNPs can also be used to create a set of coordinates with genetic changes to the survey, both inside and on the dog. This effort revealed that the individual has maintained delivery of large amounts of genetic variability, despite their long history of limited breeding.

In practical terms, this means that efforts to seek a future of disease genes in dogs can be much narrower in scope than comparable human studies, which requires a small number of genetic markers and DNA samples collected from blood or cheek from only a few hundred dogs.


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