Because all individuals in a dog or cat breed are related to each other, you might assume that any health problems are the result of inbreeding. Not so, says Bell, who notes that experiments with laboratory animals show that repeated matings between full siblings over generations will cause many family lines to die out because of infertility and genetic defects—and others to thrive. The results depend entirely on whether a particular family line propagates or loses disease-causing genes in successive generations.
What does produce inherited disease in our pets is the unchecked propagation of defective genes.
Most breeders do the right thing as best they can, says Leslie Lyons, a professor of genetics at the UC Davis School of Veterinary Medicine. From chatty Siamese to sunny golden retrievers, she says breeders create “beautiful animals with wonderful personalities and traits,” including ones that are quite useful, such as bomb-sniffing dogs.
“But everybody—whether you’re a dog, cat or human being—carries different genetic mutations,” she says.
For example, the Afrikaner population in South Africa has an unusually high incidence of Huntington’s disease, the inherited neurodegenerative disorder, because most are descendents of a small group of Dutch settlers, one of whom carried that gene.
In livestock, genetic health is considered vital to quality control, notes Bell. “It’s only in dog and cat breeding that we have had a long history of pairing mates without any regard to their genetic health.” As a result, he says, “we see diseases in cats and dogs that should have been prevented over and over again.”
Inherited health problems don’t hound only purebred animals. Thirteen of the most common hereditary disorders in dogs—including degenerative hip disease, an eye condition that causes blindness, some cancers and slipping kneecaps—occur with equal frequency in mixed-breed and purebred animals, according to research done at UC Davis and just published in the “Journal of the American Veterinary Medical Association.”
It’s not unusual to see inherited diseases in mixed-breed animals—be it a randomly bred mongrel or a designer breed such as a Labradoodle (Labrador retriever crossed with a poodle)—because they are “ancestrally down line from where those original mutations occurred,” Bell says. “Frankly, if we said today that every animal that is a carrier or has a genetic disorder can’t be bred, we might as well just go ahead and say goodbye to domestic animals.”
Origins of Canine Disease
First domesticated more than 15,000 years ago, the dog, more than any other animal, has been defined by artificial selection, says Lyons, who will speak at the Tufts Canine and Feline Breeding and Genetics Conference Sept. 27–29 in Boston.
Humans tamed wolves and then almost immediately began selecting from within this small group of founders for ones that were good for protection or hunting. “We then further refined hunting dogs to be masters at specific types of hunting,” Lyons says, such as breeding to produce experts at pursuing quarry into holes.
Distinct dog types appeared 3,000 to 4,000 years ago. Modern breeds, however, trace their roots to much smaller groups of individual animals chosen over the last couple of centuries, when it became popular to raise dogs with specific physical attributes for showing.
“It took only a handful of dogs to establish each breed,” says Noriko Tonomura, a research assistant professor at the Cummings School who conducts research at the Broad Institute of MIT and Harvard, where scientists are studying the DNA of purebred dogs to gain insight into how cancers, diabetes, cardiovascular problems and other diseases develop. “To use a very crude analogy, each breed is like a population expanded from a few families of humans,” she says.
The higher incidence of certain disorders in these “families” can be traced to an increase in the genes responsible for those health problems. Most often this is a result of what is known in the dog-show world as the “popular sire syndrome.” When a male dog wins championships, he often becomes a trendy stud that’s bred widely.
The effect is twofold, says Bell. “His genes—including any unhealthy mutations—are quickly multiplied and represented much more prominently than those of other males in the population. The breed also loses the diversity of those genes carried by the now-sidelined quality males.”
Genes responsible for health issues may be located near other genes that are being selected for, says Bell. For example, the genes that produce Dalmatians’ spots were located near an abnormal gene that made some dogs unable to metabolize uric acid, leading to bladder stones.
Over time, the Dalmatian completely lost the normal version of the gene responsible for uric acid metabolism, so in the 1970s, at the request of the Dalmatian Club of America, the American Kennel Club sanctioned a mating between a Dalmatian and a pointer to reintroduce the normal gene to the breed. The spots of the first generations were poor, but now, after more than 10 generations of mating their offspring with Dalmatians, the breed has perfect spots and can once again metabolize uric acid.
There was pushback from some Dalmatian breeders about allowing these dogs to be registered as purebred Dalmatians, but now their descendants are considered legitimate members of the breed.
Another example of the unintended consequences of selective breeding is the Shar-Pei, says Tufts veterinary dermatologist Lluis Ferrer. The ancient Chinese breed hovered near extinction after the Communist Revolution, when keeping pets was considered a bourgeois luxury. (Pets in China were taxed heavily at first, and later exterminated.) In the early 1970s, a Chinese businessman pleaded with American dog fanciers to import the few remaining Shar-Pei to save the breed.
Today American Kennel Club statistics list the Shar-Pei as the 52nd most popular breed in the United States, with most of these dogs descended from the handful of Shar-Pei that arrived from China 40 years ago. However, because of selecting for fashionable heavier wrinkles from within this small group of founders, the western Shar-Pei carry a genetic mutation that both creates the skin folds and predisposes some dogs to periodic fever syndrome, which can lead to kidney or liver failure.
Genes that predispose certain breeds to disease also can increase in a population when breeders select for certain physical traits. Breeding for extremely short, baby-like faces in bulldogs, pugs, Boston terriers and Pekinese can result in brachycephalic complex, in which narrowed airways cause breathing problems, overheating and even collapse.
“Most of the extreme physical traits we see are not called for in the breed standard,” which is each registry’s official guidelines for what a dog or cat in the breed must look or move like, says Bell. The problem instead lies with the “more-is-better” philosophy of some breeders, show judges and members of the public.
Bell says it’s important for veterinarians and breeders to work together to avoid such extremes. Brachycephalic complex, for example, is caused by such physiological factors as the length of the dog’s muzzle, the width of its nasal openings and the diameter of its windpipe. “Researchers have determined that the width of the nasal openings should be one-third the width of the entire nose in order to allow the passage of air,” says Bell. “We also know what a normal diameter of the trachea should be in proportion to a dog’s third rib.”
This means that breed clubs, which promote their mandated premating genetic screening through the Canine Health Information Center, could encourage breeders of dogs at risk for brachycephalic complex to have the nasal openings of all prospective canine parents measured and tracheas X-rayed to promote the mating of dogs with healthy anatomies.
True to their reputation for independence, cats have resisted genetic meddling, until recently.
“They essentially self-domesticated,” says Lyons, of UC Davis. “Cats began hanging around humans about 5,000 years ago, drawn by the easy access to rodents, which hung around our grain stores. And up until the 1800s, cats did what they are good at, and nobody really messed with them.”
This has given dogs a considerable head start in the genetic mutation arena, as has the fact that cat owners generally spend less on their animals. “About 90 percent of U.S. cats are randomly bred, with just a very small percentage of fancy-breed cats,” says Lyons. “For dogs, the converse is true. Complete mongrel dogs are actually very hard to find in the U.S. at this point.”
But give pedigreed cats just a little more time, and they’ll quickly catch up in the genetic-problems department, predicts Lyons. “We’re getting there with Persians,” she says, noting that indiscriminate selection for a short face has produced many animals with watery eyes prone to bacterial infection as well as misaligned bites and difficulty breathing.
One upside to inherited health problems is that “the hallmark of genetic disease is predictability,” says Bell. “If you can diagnose a genetic disease even before its onset, we can often intervene and either prevent or slow that progression.” A severe case of hip dysplasia can be prevented if a puppy is diagnosed early enough. “Surgery has to be done before any bony changes occur,” he says.
Thanks to the sequencing of the canine genome, or hereditary map, in 2005 and the feline genome in 2012, researchers have begun to identify the mutations responsible for many inherited diseases.
For boxers, which can develop an abnormal heart rhythm that leads to cardiac failure, “we now have a genetic test that will tell us which dogs are prone to developing that arrhythmia,” says Bell. “I test all boxers when they’re young to determine if they have that gene. If they do, we monitor their heart rate and rhythm, especially between four and eight years of age, when the arrhythmia usually begins to develop. As soon as we see it starting, we can put the dogs on a drug that prevents the abnormal heartbeat, which means they’ll never go into heart failure.”
Other breeds—including collies, Shetland sheepdogs, Old English sheepdogs and Australian shepherds—have a mutation in the gene called MDR1, which helps the animals metabolize drugs. If dogs with two copies of that mutation receive drugs commonly used to prevent heartworm or treat diarrhea, they can experience seizures or die. “Veterinarians can and should test all breeds that may carry that mutation before using any of the potentially toxic drugs,” says Bell.
Some Doberman pinschers, Shetland sheepdogs, poodles and members of several other canine breeds carry defective genes linked to von Willebrand disease, a bleeding disorder similar to inherited hemophilia in humans. Bell notes that these breeds should be tested for the mutation before surgery to avoid excessive blood loss.
Of course, genetic testing does not always stave off inherited disease. Researchers have discovered genetic mutations in Maine coon and ragdoll cats associated with cardiomyopathy, a thickening of the heart muscle that leads to heart failure. But not all cats with the genetic defect develop heart disease, says Lyons. And all veterinarians can do for those that do is to try and slow the progression of the disease.
An Ounce of Prevention
The most effective medicine for treating genetic disease is to stop dogs and cats from being born with those diseases in the first place.
“If you’re trying to produce healthy animals, you need to breed healthy parents,” says Bell, who raises Gordon setters. “And if we work to improve how pets are bred each year, we can very quickly and significantly diminish the number of animals with genetic illness.”
There is good news to report. Bell says that over the past decade, canine registry-required genetic testing has resulted in significant reductions in progressive retinal atrophy, an eye condition leading to irreversible blindness in many dog breeds, including Portuguese water dogs, English cocker spaniels and Nova Scotia duck tolling retrievers. The most recent statistics from the Orthopedic Foundation for Animals show a 25 percent reduction in hip dysplasia over the past five years versus historical averages across all breeds.
Breeders of Burmese cats have used a new genetic test to nearly eradicate a type of hypokalemia (abnormally low potassium levels associated with severe skeletal muscle weakness) in just one year, Lyons says.
Unfortunately, an impulsive pet-buying public often enables irresponsible breeders who ignore recommended genetic tests and screenings.
“If a breeder who skips genetic screening can put an ad on the Internet and people will still send them thousands of dollars to buy a puppy or kitten, what’s the impetus for them to be health conscious and do the right thing?” says Bell. “And, sadly, people will spend much more time researching what computer to buy than finding a healthily bred pet.”
By asking for test results from a purebred animal’s parents, owners not only end up with healthier pets; they also create a higher demand for responsibly bred dogs and cats. If official test results are not available, it’s time to find a different breeder, advises Bell.
Finding a healthy puppy or kitten from a responsible breeder may take up to six months. This means you may not get the breed you want “off the shelf” as soon as you’d like. But given that a pet may be part of your family for 15 years or more, it’s worth the wait, Bell says.
Although “a lot of irresponsible breeders have a health guarantee,” Bell says, “what that guarantee states is that they will replace the animal with one of equal quality if any genetic defects occur. But pets aren’t toasters. Once an owner purchases an animal, that emotional bond develops within the first five minutes. If something goes wrong, most owners are not going to say, ‘OK, I’ll give it back, and I’ll get another one.’ A pet is part of the family at that point.”
Genevieve Rajewski can be reached at email@example.com. This article first appeared in the Summer 2013 issue of Tufts Veterinary Medicine magazine.