Matthew Breen is a rogue gene hunter whose job involves encounters with potential killers. And Breen, who's British, has the foreign accent to give his white lab coat an adventurous tinge.

Rogue genes are instructions inside a cell that are associated with disorders such as blindness, narcolepsy and cancer. They lurk in the human genome, but they are difficult to find because they can hide in the crowd. The human cell has about 25,000 genes that vary too much from person to person for one mutation to stick out.

But rogue gene hunters such as Breen have figured out a way to simplify the task. They found a genome that's up to 95 percent similar to that of humans without the variability - the 19,000 or so genes of purebred dogs.

"Looking for genes that go wrong in human diseases is like trying to see the wood for the trees," said Breen, a professor of genetics at the N.C. State University College of Veterinary Medicine. "With dogs, it's more like national forests planted in rows. If there's one tree out of line, you can see it."

Case in point: A team of Spanish, French, Swedish and American researchers found a clue for unexplained, periodic bouts of autoinflammatory disease that strike about 60 percent of fever patients. They discovered it in the thick skin folds of Chinese Shar-Peis.

Dogs have lived beside humans for about 15,000 years, longer than any other domesticated animal. Highly developed cultures in Asia and Africa started selectively breeding dogs for hunting and protection thousands of years ago. Some of the oldest breeds are runners such as the Afghan hound or the Saluki, also known as the royal dog of Egypt or Persian greyhound.

Europeans followed suit hundreds of years ago, first to breed dogs for a specific job such as controlling rodents or herding livestock, and later for appearance.

Breeding genetic conformity

Selective breeding and inbreeding over generations have resulted in dog breeds with highly conforming genomes. Terriers are known for their feistiness and wiry coats. Herding dogs are intelligent and can control the movement of other animals. Great Danes are large dogs with short coats. Pomeranians have long, fluffy coats and are small enough to fit into a purse.

Genetic conformity makes a breed. In the past 40 years, the thick skin folds have come to define Shar-Peis in the West.

But desired looks and characters also can make a breed susceptible to certain ailments, including diseases that affect humans.

In the case of the Shar-Peis, it's hyaluronic acid. The molecule causes the skin folds, but it's also an inflammatory. Bred to have multiple copies of the gene to instruct the cell to make extra hyaluronic acid, the dogs become susceptible to periodic episodes of inflammation and fever.

"You end up emphasizing the good side, but the downside, the mutations, are also emphasized," said Christine Haakenson, a biochemist and the director of research at the Canine Health Foundation, a nonprofit that shares offices with the Raleigh-based American Kennel Club.

Diseases in humans and dogs

As many as one in four Bernese mountain dogs develops malignant histiocytosis, a disease of the lungs and lymph nodes that is also hereditary, though rare, in humans. The Briard dog, a French herding breed, is susceptible to congenital stationary night blindness, an inherited retinal disease that's similar to Leber's congenital amaurosis in children. And the same mutant gene causes dementia and loss of muscle control in Tibetan terriers and a neurological disorder related to Parkinson's disease in humans.

To help purebred dogs suffering from the unintended consequences of human genetic tinkering, the foundation has provided $25million to researchers since 1995. The National Institutes of Health also pitched in.

Breen has received grants from both organizations. The NIH provided $1million for research he and a team of U.S., Scottish and Swedish scientists did on non-Hodgkin's lymphoma - a clinically diverse human cancer that also affects about 300,000 dogs every year, including golden retrievers.

The underlying genetic risk factors for the wide range of lymphomas are thought to be many, making pinning them down in the human genome impossible.

In purebred dogs, however, lymphoma is about five times more prevalent than in humans. Certain types of lymphoma run in certain breeds, suggesting that certain genetic risk factors are associated with certain varieties of lymphoma.

With that, Breen's team analyzed genetic samples of about 150 purebred dogs with lymphoma, including golden retrievers, Labrador retrievers, boxers and 18 other breeds. In a paper published in the journal Leukemia & Lymphoma, the team described what it discovered when it took rogue dog genes it found and located the corresponding human genes: Genetic risk factors for lymphoma clustering on two of the 23 human chromosomes.

"In essence, we stripped the background noise from the human data," Breen said.

The research results suggest "that maybe there is a lot of genetic noise in the human cancers that are not essential components of the process."

With a possible molecular signature at hand, the team can now look at what havoc the faulty instructions may wreak. And that could lead to the development of treatments for both human and canine lymphoma patients.