geneticist's best friend
are leading the pack in the hunt for the causes of inherited diseases,
reports science writer Leigh Dayton
from: The Australian <http://www.theaustralian.news.com.au/> .
dogs such as Ned don't just chase balls, wag their tail and pose
perfectly in the judging ring. Increasingly, they're teaming up
with scientists such as Alan Wilton in the search for genes behind
inherited diseases, human and canine.
now, Ned and Wilton -- a dog geneticist with the University of NSW
-- are tracking genes that cause a specific type of deafness in people
and Australian cattle dogs. If they can locate the genetic source
of the problem, that will be good news for pooches and people. ``We
want to identify the genes responsible for the condition in dogs
to better understand the biology of the disorder to help humans,''
Wilton explains. ``We also want to develop genetic tests that detect
carriers in dogs so breeders can eliminate the problem. With a test,
we could stop this disease being present in future generations.''
took decades of work by dedicated pioneers such as Elaine Ostrander
-- with the US National Institutes of Health in Bethesda, Maryland
-- to prove what's now obvious to researchers worldwide: dogs are
a geneticist's best friend. For starters, humans have a penchant
for sharing genes indiscriminately. Purebred dogs don't. Their
reproductive activities are controlled by breeders seeking to inbreed
to University of Sydney geneticist Peter Williamson, that simplifies
the job of identifying the genes that produce those traits, from
physical characteristics such as coat colour to propensity for
inherited diseases. ``The breed structure has scientific power
because in humans the populations are complex and the genetics
all scrambled,'' says Williamson, leader of the Canine Biobank
Project in the faculty of veterinary sciences. In other words,
there are far fewer variations in target genes in purebreds such
as Ned -- Warrukadli Rebellion on his birth
certificate -- than among people. That means it's necessary to
trawl through the entire genetic complement, the genome, of far
fewer dogs than people to get a hit, Williamson says.
example, if a disorder is caused by a single mutation at one spot
on a gene, it could be identified in as few as 10 pedigree dogs,
but would require genetic material from thousands of people. ``In
complex disorders like diabetes, the numbers go up to 100 to 200
dogs but that's instead of 10,000 to 20,000 humans,'' Williamson
another reason pedigree dogs are rapidly becoming the model animal
of choice. As Wilton says, ``people love their dogs''. They take
them to the vet, who keeps records, and breeders document genealogies.
Having such detailed health and genetic records helps speed up
the search for mutations that cause serious diseases, for dog and
to data complied by University of Sydney emeritus professor Frank
Nicholas -- creator of the Online Mendelian Inheritance in Animals,
hosted by the NIH -- about 440 inherited disorders have been identified
in dogs and 6000 in people. Most are so-called single gene disorders.
Many affect both species. Researchers suspect that many complex
diseases are also likely to be shared. In fact, the top 10 diseases
affecting dogs include diseases that affect millions of people
across the world: cancer, epilepsy, allergy and heart disease.
Moreover, Williamson notes that dogs and people share the same
environment: ``For instance, as humans get fatter, so do their
pets. Somebody has to hand them the food.''
pudgy pet-pudgy person connection holds promise for unravelling
the underlying mechanisms of adult onset, type 2 diabetes. ``Dogs
don't seem to get type 2 diabetes even if they're obese. It's over-represented
in humans,'' Williamson says.
there must be a genetic component to the difference. If geneticists
can find what that is in dogs, it may well reveal details of the
human version of the disorder, which accounts for up to 90 per
cent of all cases of diabetes. Such insights could suggest directions
for new treatments, possibly gene therapy though which defective
biochemical processes and pathways are corrected.
the potential for humans of dog genetics is ``quite profound'',
as Williamson puts it, the field is in its infancy. As suggested
by Nicholas's OMIA data, most of the inherited diseases of Canis
familiaris domesticus and Homo sapiens that have been traced to
their genetic foundations are caused by mutations in a single gene.
Little wonder, then, that the genes for human diseases found by
detecting them first in dogs are the cause of very rare disorders.
``There are two well-known cases,'' says Wilton, pointing to the
Hcrtr2 gene that causes a form of narcolepsy in dachshunds, labrador
retrievers, doberman pinschers and people. Animal and human sufferers
are prone to the sudden onset of sleep during waking hours.
second landmark case was the discovery of the genetic defect causing
a form of blindness called progressive rod-cone degeneration. ``It's
the cause of blindness in humans, but only in a small number of
cases,'' Wilton says. ``Gene therapy can probably be developed
to restore the sight of blind dogs,'' he adds, noting that, if
so, human trials could soon follow. After all, the treatment would
have been tested first in an animal model, a prerequisite for trials
and his colleagues have already tracked down the genes behind a
deadly disease affecting puppies and babies. They've patented a
genetic test for the dog version -- neuronal ceroid lipofuscinose
disease -- which strikes about one in 1800 purebred border collies,
as well as english setters, some cats and ferrets.
human form, Batten disease, hits about three in every 100,000 children.
There's no cure or treatment for the neurodegenerative disorder.
So while Wilton says testing will completely eliminate the dog
form in time, he hopes the findings will be applied to people.
and co have other projects on the go, among them the search for
the gene defect causing ataxia -- shaky movements and unsteady
gait -- in kelpie dogs and probably in people. They're also working
with border collies to pinpoint the mutations behind the eye disorder
glaucoma, which affects mostly older people.
the University of Sydney, Williamson and his colleagues Rosanne
Taylor and Claire Wade are also tackling a range of immune, allergic
and neurological disorders affecting people and dogs. It's all
part of what Williamson calls ``one medicine'', the use of powerful
new genetic technology that enables scientists to compare and contrast
the genomes of people and pedigree pooches. Such advances help
them search, sequence and screen samples of genetic material; they
also have plenty of data. Four years after international scientists
completed the human genome project in 2001, another international
consortium, led by geneticist Kerstin Lindblad-Toh with the Broad
Institute of Harvard and the Massachusetts Institute of Technology,
laid out and ordered the dog genome. As Wilton said at the time:
``The genome is like an encyclopedia. It's an awfully good resource
for future work.'' Scientists worldwide are adding entries to the
encyclopedia through projects such as Williamson's Canine Biobank,
which began taking doggie DNA deposits early this year.
Sydney Biobank is but a pup compared with the Lupa consortium,
named after the wolf that, legend says, suckled the founders of
Rome. Scientists from 20 European institutions plan to obtain DNA
samples from and genealogical and health records on 8000 dogs.
``It's still early in the piece, but we're already seeing a marked
upswing in this kind of work,'' claims Williamson. Like Wilton
and all the international teams working on dog genetics, he predicts
results for both species soon. Rightly so.
Lindblad-Toh said when her group published details of the dog genome:
``For millennia, dogs have accompanied humans on their travels.
It is only fitting the dog should be a valued companion on our
journeys of scientific discovery.''