Dog genome boosts cancer research

By Melissa Lee Phillips

Tied by 15,000 years of companionship and genetics

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 Matthew Breen, of North Carolina State University in Raleigh.

DOG DNA - CANIS FAMILIARIS The double-stranded DNA molecule is held together by four chemical components, or bases Adenine (A) bonds with thymine (T); cytosine(C) bonds with guanine (G) Groupings of these letters form the "code of life"; there are estimated to be about 2.4 billion base-pairs in the dog genome wound into 40 distinct bundles, or chromosomes Written in the DNA are possibly 25,000 genes which dog cells use as starting templates to make proteins; these sophisticated molecules build and maintain the animal's body

"Some breeds of dogs have a much higher risk for particular tumours than other breeds," explained Jaime 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, Maryland.

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.

German shepherds have led to knowledge of a kidney cancer-causing gene

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."