A Search of the Canine Genome May Aid in Cancer Research

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Dog genome boosts cancer research

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We have shared our lives with dogs for thousands of years, and our

relationship is only getting closer.

The complete canine genome sequence, which was finished last summer,

is helping scientists to track down genes that cause disease in both

dogs and people.

" We share our genes and we share our diseases, " said Kerstin Lindblad-

Toh, of the Whitehead Institute Center for Genome Research in

Cambridge, Massachusetts, US.

Many researchers are hopeful that the dog genome will reveal

important genes behind the cancers that afflict us and our closest

companions.

Bone cancer, skin cancer, and lymphoma are among the many types of

cancers that are similar in humans and dogs.

We share our genes and we share our diseases

Kerstin Lindblad-Toh

The genes that cause them will probably be easier to track down in

the dog genome, however. Breeders have selected dogs for specific,

homogeneous features, so each dog breed has very little diversity in

its genes.

Also, many breeds arose from just a few founder dogs, went through

population bottlenecks, and experienced popular sire effects, when a

particularly desirable dog fathered an excessive number of puppies.

Small gene pool

Because of these restricted gene pools, many dog traits, including

cancers, are " being switched on by very few genes - maybe even just

one - which exert a very large effect, " according to geneticist

Breen, of North Carolina State University in Raleigh.

" Some breeds of dogs have a much higher risk for particular tumours

than other breeds, " explained Modiano, a cancer biologist at

the University of Colorado Health Sciences Center in Denver.

For example, boxers, golden retrievers, and St Bernards have high

rates of lymphoma; whereas Great Danes, Irish wolfhounds, and other

large breeds are predisposed to bone cancer.

In order to figure out where a cancer-causing gene is located in an

animal's genome, scientists use genetic " markers, " which are

sequences that differ slightly between different dogs and have a

known location on a chromosome.

When disease-affected animals consistently have a certain marker, and

healthy animals do not have it, then there is a good chance that a

disease gene is located very close to that marker.

These analyses are difficult to do in humans, because geneticists

need to look at DNA samples from many people in an affected family in

order to pin down the gene's location.

Most human families are too small - and have too few generations

alive at the same time - for a sufficient number of samples. Dog

families, on the other hand, have short generations and many

offspring.

Scientists have already had success locating a gene responsible for

kidney cancer.

German shepherds

" It turns out to be the same gene causing a very similar clinical

presentation " in both dogs and humans, said Elaine Ostrander, chief

of the Cancer Genetics Branch of the US National Human Genome

Research Institute in Bethesda, land.

Using a large pedigree of German shepherds, Ostrander's group tracked

down the cancer-causing gene on canine chromosome 5.

When they looked in the comparable region of the human genome, they

found a gene that had recently been implicated in human kidney

cancer.

These types of gene hunts have become easier with the recent

completion of the entire dog genome sequence. The sequence was

deposited into public databases in July and will be published, along

with an analysis comparing it with the human sequence, sometime this

spring.

Dogs' " genome structure suggests that we can find the disease genes

pretty quickly now that we have the genome " , said Lindblad-Toh, who

led the sequencing effort.

" Pretty quickly " will likely be over several years, not several

months, she warned.

Knowing a gene's location and sequence will help to predict cancer

risk and diagnose cancer in both humans and dogs. Clinical trials

were also underway to try to treat some of these cancers by blocking

the biochemical pathways thought to be involved, Modiano said.

An almost certain result of dog genome cancer studies is the

identification of disease genes that can be bred out of affected dog

breeds.

" Breeders have shown a real willingness to get genetic tests and to

redesign their breeding programmes, " Ostrander said. " I really see

the impact being healthier, more long-lived dogs. "

Story from BBC NEWS:

http://news.bbc.co.uk/go/pr/fr/-/1/hi/sci/tech/4106163.stm

Published: 2004/12/29 12:30:46 GMT

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