Genetic Testing for prcd-PRA Is Recommended Before Breeding
A healthy, active Golden Retriever who recently retired from agility competition, "Daphne," at age 8 ½, has earned many titles, including Master Agility Champion, to prove her success: MACH Pine Run A L'il Daph'll DoYa, WC, AAD, OD, ADHF, OF.
Likewise, "Trevor" is a healthy, active Golden Retriever. This 3-year-old, who is working toward becoming a Master Agility Champion, has also earned many noteworthy titles: Emberain Trevolution, PD2, CL3 [MX MXJ XF RA CGC], SPD.
Trevor and Daphne share more than agility titles. They also share a future in which progressive retinal atrophy (PRA), an eye disease that usually leads to blindness, is predicted by their DNA.
PRA has several different forms, but progressive rod cone degeneration (prcd-PRA) is the most widespread
in terms of the number of breeds it affects. This is the type of PRA that Daphne and Trevor have. The same recessive gene also causes prcd-PRA in Labrador Retrievers and more than 20 other breeds.
The age at which signs of prcd-PRA become noticeable varies. Since Daphne and Trevor are among the first Goldens to be positively identified with prcd-PRA through DNA testing, nobody knows when signs typically appear.
"Experts so far believe that signs of PRA in Goldens are visible by physical eye examination between 3 and 6 years of age," says Daphne's co-breeder, Gerry Clinchy of Coopersburg, Pa.
If Daphne is any indication, behavioral signs in Goldens are late compared to other breeds. At 8 ½ years old, Daphne is only now exhibiting subtle signs.
"I notice Daphne's diminished sight in the evening," says owner Mardi Closson of Schnecksville, Pa. "I also started noticing sometime last year that she was a little hesitant when running agility, especially when climbing the dog walk if a tunnel was next to it. The angle of the sun and that combination seemed to cause her to be unsure what to do."
In prcd-PRA, retinal receptor cells responsible for vision develop and function normally in early life, but at some point in mid to later life they degenerate and die. These receptor cells are two types: rods and cones. The rods, which are responsible for vision in low light levels, die first; thus, affected dogs initially have difficulty seeing in dim light. Eventually the cones, which are more important for detail, movement and color vision, follow. The dog gradually loses vision in bright light too, until becoming completely blind.
Physical signs of prcd-PRA are determined by ophthalmoscopy, and electrical signs are detected by electroretinography. Both appear much earlier than behavioral signs. Owners may notice that the eyes glow more than normal. This occurs as the receptor cells die, leaving the retina thinner and thus allowing the shiny tapetum behind it to show through more. In addition, the pupil compensates for the lack of light reception by opening up wider. The added effect of the wider pupil and brighter tapetum makes the dog's eyes glow to the point that owners may be the first to notice something different. More often, however, it has been a routine eye examination that leads to discovery of the problem.
Breeders Take Action Closson discovered Daphne's condition when a routine CERF (Canine Eye Registration Foundation) examination performed in preparation for the Golden's second breeding indicated PRA. The ophthalmologist said he hadn't seen a case of PRA in a Golden in years. A second opinion with one of the leading PRA experts, Dr. Gustavo Aguirre of the University of Pennsylvania, confirmed the diagnosis and resulted in a DNA sample being sent to OptiGen for analysis. It came back positive for prcd-PRA.
Daphne wasn't the first Golden with PRA to be DNA tested, but she was the first of 20 or so to be tested in which the PRA was identified as prcd. Some breeders may have kept the news to themselves, reasoning the condition must be rare so the chance of matching up with another carrier would be slim. But Closson and Clinchy took action, encouraging people who owned dogs from Daphne's bloodline to be DNA tested.
As expected, all her offspring were carriers. The good news is that DNA testing allows carriers to be bred, as long as they're bred to genetically clear dogs. So when an inquiry came for stud service to one of Daphne's male offspring soon after she was diagnosed, they informed the owner of the bitch of the circumstances.
"Though the bitch was totally unrelated, her owner understood that it was an essential precaution to test her bitch if she intended to breed to a carrier of the prcd gene," says Clinchy. "That's when we, just by accident, found that this other bitch was also a carrier. We had all anticipated there would be other Goldens with the gene mutation, but we were stunned one was found so soon after Daphne.
"Since this new carrier incorporated lines that were more widespread than Daphne's, it raised the interest level. As the owner shared the test results of her dog, other owners and breeders felt it would be a wise precaution to start testing some of their dogs as well."
Now, more than 1,000 Golden Retrievers have had the DNA test, with six identified as being affected and 204 as carriers. Many of the carriers were tested solely because they were related to an affected dog, thus the total number of carriers may overrepresent the prevalence of prcd-PRA in the breed.
"PRA in Goldens is still believed to affect less than 1 percent of the whole population of Golden Retrievers," Clinchy says.
Finding affected dogs is complicated partly by the fact that not all dogs will be examined by a veterinary ophthalmologist. Not only is it difficult to know the prevalence of PRA in Goldens, but also the prevalence of prcd compared to other types of PRA in Goldens.
In dogs, DNA tests are available for at least eight different types of PRA, but many breeds have forms of the disease that have not yet been identified. PRA is considered to be the canine version of retinitis pigmentosa in humans, which is known to have more than 100 identified genetic mutations — all resulting in identical clinical signs.
"PRA in dogs probably follows a similar pattern," explains Sue Pearce-Kelling, president of OptiGen and a former Golden Retriever breeder. "There are likely to be hundreds of mutations responsible for different forms of PRA. Prcd-PRA is unusual in its widespread distribution across many breeds, indicating it is an old mutation that was probably present before modern breeds segregated."
Practicing Prudent Breeding Experts advise not to breed Golden Retrievers with unidentified causes of PRA since there is no way to avoid the possibility of breeding to a carrier. OptiGen statistics suggest that the major form of PRA in North American Goldens is prcd-PRA, whereas another unidentified form of PRA is more prevalent in European Goldens, Pearce-Kelling explains.
"Of the 204 prcd-PRA carriers tested so far, 184 are from North America, and the only two clinically affected Goldens that had prcd-PRA are from the U.S.," she says. "In contrast, we've received three clinically affected Goldens from Europe that do not have prcd. There is also a large database of Swedish Goldens with PRA, but it's not prcd-PRA."
In an effort to find unidentified gene mutations, OptiGen offers free testing for Golden Retrievers or any breed definitely diagnosed with PRA. Most of the dogs so far tested are from field trial lines, probably because the first dogs identified with prcd were from field lines.
"As far as I know all the dogs that have been identified as having the prcd gene are from field lines," says Clinchy. "Field breeders have been in the forefront of testing, and that's resulted in us now having identified at least 11 different family groups that carry the gene in North America and four families in Europe."
Because the same gene causes prcd-PRA in so many breeds of dog, including other retrievers, it's probable that the mutation was part of the Golden's heritage when the breed was created and thus would be found in field, show and even companion Golden Retrievers.
Whether from CERF or DNA results, the news that a dog is affected by PRA is devastating. Katie McCormick of Redwood City, Calif., tested Trevor's DNA because she'd learned he might be at risk. Still, she was unprepared for the news.
"I was training Trevor to do agility, and he was doing so well," she says. "I mourned the loss of my illusion of the perfect dog. Knowing helped me to get serious and focused about my performance goals for Trevor."
Daphne's owner Closson agrees. "When I think of knowing about the PRA versus not, I'd rather know so I wouldn't put her in harm's way. If I hadn't known about the sight issue and had experienced the hesitation on the dog walk in agility, I probably would have been frustrated wondering what was causing it. I might have continued to try to work it out, and she might have been injured. While I certainly wasn't happy to have the prcd-PRA issue appear, knowing what I was dealing with was much better than not."
"I don't think that anyone would ever knowingly pick out a puppy with PRA," McCormick says. "But I wouldn't trade Trevor for anything in the world. He is the cutest, smartest, sweetest, most talented dog I know."
Neither owner has given up hope that their dogs will retain some sight, but they're prepared to cope otherwise. "If that's not the case," says Closson, "then it's my job to make sure Daphne can be as comfortable and happy without her sight. Her happy-go-lucky disposition assures me she will be just fine."
It Takes A Village
The discovery of prcd-PRA in a top-performing agility Golden Retriever united the dog's breeders and owner in an effort to increase awareness of the disease and encourage other breeders to submit blood samples for DNA testing. Their hard work helped to diminish the potential prevalence of a devastating eye disease.
"The influence of these highly respected breeders was pivotal in encouraging more and more breeders to start testing their dogs," says Gerry Clinchy of Coopersburg, Pa., co-breeder of "Daphne" (MACH Pine Run A L'il Daph'll DoYa, WC, AAD, OD, ADHF, OF). "I can't say enough about the breeders who also tested frozen semen from important sires now deceased. It gave valuable information."
Clinchy credits Jim Drager, the owner of Daphne's sire, for contacting all the breeders who had used the sire and encouraging them to have their dogs tested and to notify owners of offspring. Others key to the effort were Pat Sadler, Renee Schulte, Jackie Mertens and Judy Rasmuson. Chris Miele, past president of the Golden Retriever Club of America (GRCA), helped notify the parent club of the finding, and Daphne's owner, Mardi Closson, was "at the epicenter" of the effort, Clinchy says.
Thanks to the awareness campaign, the Golden Retriever Foundation approved underwriting the cost of collecting blood samples at the GRCA National Specialty and shipping them to OptiGen for PRA testing.
A new Web site — www.goldendna.com — was created so breeders could share PRA test results at no cost with a worldwide audience. Golden Retriever breeder Dean Lake volunteered to manage the site she initially funded along with Clinchy. So far, nearly 400 Golden Retrievers are listed on the Web site.