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Dog
Genome May Shed Light On Human Disease
By Tom Harrison
Scientists
have succeeded in sequencing the dog genome, an accomplishment that
could lead to better health for humans as well as canines. An
international team of researchers have published their detailed
analysis in the journal Nature.
"Of
the more than 5,500 mammals living today, dogs
are arguably the most remarkable," says senior author Eric Lander, PhD,
director of the Broad Institute at 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 -- is encoded in their
genomes. It can uniquely help us understand embryonic development,
neurobiology, human disease and the basis of evolution," Dr. Lander
notes.
Powerful
Tool
"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," says Francis S. Collins, MD, PhD, 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,"
Dr. Collins adds.
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. From six-pound Chihuahuas to 120-pound Great Danes, from
high-energy Jack Russell Terriers to mild-mannered basset hounds, and
from Shetland sheepdogs with their herding instincts to pointers
inclined to point, humans have bred dogs for desirable physical and
behavioral traits.
Such breeding practices preserve preferred traits
of one generation in the next, but they also predispose many dog breeds
to genetic disorders, including heart disease, cancer, blindness,
cataracts, epilepsy, hip dysplasia and deafness.
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.
Evolutionary
Tree
While dogs occupy a special place in human hearts,
they also sit at a key branch point, relative to humans, in the
evolutionary tree. It was already known that humans share more of their
ancestral DNA with dogs than with mice. The availability of the dog
genome sequence has allowed researchers to describe a common set of
genetic elements -- representing about 5 percent of the human genome --
that are preferentially preserved among human, dog and mouse.
Rather than being evenly distributed, some of these
elements are crowded around just a small fraction of the genes in the
genome. Future studies of these clusters may give scientists the
critical insight needed to unravel how genomes work.
Elaine A. Ostrander, PhD, chief of NHGRI's 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 is the lead author of the white paper that sets
forth the biomedical rationale for sequencing the dog genome.
Dr. Ostrander's laboratory maps genes responsible
for susceptibility to cancer -- including breast and prostate cancers
-- in canines and humans.
"The leading causes of death in dogs are a variety
of cancers, and many of them are very similar biologically to human
cancers." says 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."
Genetic
Compass
Efforts to create the genetic tools needed for
mapping disease genes in dogs have gained momentum over the last 15
years, and already include a partial survey of the poodle genome. More
than two years ago, Kerstin Lindblad-Toh, PhD, co-director of the
genome sequencing and analysis program at the Broad Institute, and
colleagues embarked on a two-part project to assemble a complete map of
the dog genome.
First, 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 the coyote.
The researchers identified roughly 2.5 million
single nucleotide polymorphisms, or SNPs, 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.
In practical terms, this means that future efforts
to locate disease genes in dogs can be much narrower in scope than
comparable human studies, requiring a smaller number of genetic markers
and DNA samples collected from the blood or cheek from only a few
hundred dogs.
About the Author: Tom Harrison is a health
journalist for Daily
News Central, an online publication that delivers breaking
news and reliable health information to consumers, healthcare providers
and industry professionals.
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