pcrd-PRA Testing |
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General Information
New Genetic Advantage: prcd-PRA Testing for Toy and Miniature Poodles by Jeanette S. Felix, with contributions from Mary M. Woodsen
The new genetic test for the prcd form of Progressive Retinal Atrophy (PRA) gives breeders of Toy and Miniature Poodles a long-awaited breakthrough in sight. For almost two decades veterinary ophthalmologists Gustavo Aguirre, DVM, PhD, director of the Center for Canine Genetics at the Baker Institute, Cornell University, and Gregory Acland, BVSc, senior research associate at the Center, have been searching for genes that cause the various forms of canine PRA. Those years of hard work are paying off with new genetic tests for a variety of PRA diseases. PRA is a cluster of related heritable diseases that generally cause irreversible blindness in affected dogs. To varying degrees, nearly every breed is susceptible to some form of PRA. The disease attacks the retinal tissue in the back of the eye. The retina is where specialized cells called photoreceptors convert light into chemical signals, then transmit these impulses to the brain. Photoreceptors called "rods" gather dim light, amplifying it into nerve impulses. Bright light causes other photoreceptors called "cones" (these terms describe the shapes of the cells) to shift into gear. Recognizing PRA Toy and Miniature Poodles exhibit "late-onset" PRA, usually showing the first obvious clinical signs of disease between three and five years of age. PRA attacks the rods first, and affected dogs have trouble finding their way in dim light. (Indeed, rod deterioration can happen as early as five months of age - but no one notices it.) Eventually these dogs lose their night vision. As PRA progresses, the cones come under attack. Dog owners notice that their pet's eyes take on a characteristic "shine." The pupils become increasingly dilated in the attempt to let in yet more light and dogs develop "tunnel vision." It's like trying to look at the world through a narrow tube. Often vision loss isn't noticed until much later than three years. Dogs are highly adaptable. As long as their surroundings are completely familiar, they can compensate for extreme tunnel vision by always moving their head and eyes - and by simply knowing their way around. More than one form of Poodle PRA To complicate things further, Dr's. Aguirre and Acland found at least two different genetic forms of PRA in Toy and Miniature Poodles, even though the clinical signs of PRA in all diseased dogs of this breed look exactly the same. One form cannot be distinguished from another form based on a clinical exam. Through extensive research, they showed that the autosomal recessive gene called prcd, or "progressive rod-cone degeneration" is the cause of most cases of PRA in Poodles. ("Autosomal" means the gene is on a chromosome that is not a sex-determining chromosome - the X or the Y. "Recessive" means two copies of the mutant gene - one from each parent - must be present to cause the disease.) The exact frequency of prcd-PRA compared to another type of PRA in the Poodle is not known. We do know that prcd-PRA is frequent and is the predominant form, causing 75% or more of all PRA cases in Poodles. More information on its frequency will be gathered as more dogs are tested. The prcd-PRA multiple-marker test for Poodles is now available to breeders exclusively from OptiGen. Other breeds suffer prcd-PRA as well. Specific versions of the multiple-marker test are used for Portuguese Water Dogs, Chesapeake Bay Retrievers, English Cocker Spaniels, and Labrador Retrievers. For each breed, the test is first proven effective on a large number of research dog samples obtained with the help of the breed club. What you learn with the prcd-PRA test This marker-based test uses a set of DNA "pieces" that are so close to the prcd gene they never separate from it. The exact identities of these "pieces" mark the prcd gene as normal or mutant. This test is completely accurate in diagnosing clear/normal dogs. But unlike a test that looks at the actual mutation instead of at closely associated markers, sometimes "false-allele" readings occur which incorrectly identify dogs as carriers and affecteds. A tested carrier may actually be clear, and a tested affected may turn out to be a carrier. This multiple-marker test classifies dogs into three groups, just as for other breeds tested for prcd-PRA:
*The Pattern A result is definite and absolute for prcd-PRA. But remember - a Toy or Miniature Poodle that is clear for prcd-PRA could still be at risk for having or carrying another form of PRA that is less common. False positive allele Until the actual prcd gene mutation is discovered, allowing for a direct mutation test, or until additional helpful markers can be added to the test, we must deal with the complication of the false allele. False allele readings are the result of generations of genetic evolution and change. Originally - tens of centuries ago - the prcd-PRA gene was a normal, healthy gene for retinal functioning and no PRA disease existed. At some point, the normal gene changed - mutated - in just one dog to become an abnormal gene. That mutated dog also had a certain set of markers associated with the mutant gene. It passed the mutation with the associated markers to its offspring and whenever inbreeding allowed two copies of the mutation to turn up in one dog, the disease prcd-PRA, arose. Close relatives of the original mutant dog also had the same set of markers even though their prcd gene hadn't mutated, while other dog families had different sets of markers for their normal prcd gene. Apparently, over a long time, the original dog's markers that once accompanied the normal gene are now mostly associated with the prcd mutation. But occasionally the original dog family's version of markers connected to the normal gene turns up, creating the false allele. A full explanation of the false allele is given in OptiGen's informational sources. Breeding strategies with the prcd-PRA test Breeding strategies to avoid producing pups affected by autosomal recessive prcd-PRA are straightforward. Most importantly, they even allow continued use of dogs that test either Pattern B or C. All Pattern B and Pattern C dogs should be bred ONLY to Pattern A dogs - no affected pups will be produced. In turn, pups with one A parent and the other parent a B or a C must be tested to determine its Pattern A or B status before being used in subsequent breedings. However, if a Poodle is Pattern A for prcd-PRA, but has a close relative (littermate, parent or grandparent) with a clinical diagnosis of PRA (type unknown), OptiGen strongly recommends that the relative with PRA be tested. If that relative tests non-affected with prcd-PRA or is not available for testing, the breeder should proceed as if that relative has another type of PRA and the descendent dog should not be bred due to high risk of carrying some form of PRA other than the prcd form. Testing PRA affected Poodles Research on Poodles is continuing in order to identify the remaining gene(s) that cause other types of PRA. You can help if you have a Poodle that has a documented diagnosis of PRA. OptiGen will test dogs that have a CERF or a clinical exam report by an ACVO diplomate stating that PRA has been diagnosed. The owner can submit the dog's blood sample with a copy of exam records, along with the dog's pedigree and a statement permitting use of this dog's blood sample for research purposes if it tests clear for prcd-PRA. The price for these tests will be reduced by 50%. Testing Standard Poodles for PRA Because very few cases of PRA in Standard Poodles have come to the attention of researchers, the prcd-PRA marker test has not been examined for them. It's likely that, if Standards have PRA, it would be one of the forms also present in Toys and Miniature. However, that hasn't been proven as yet. Results for Poodles used in the research For reasons of client/doctor confidentiality, scientists at the Baker Institute cannot release the test results of dogs studied during in the past research phase without specific permission from each individual owner. Owners who donated blood samples for these studies and who want their results can obtain a request form from OptiGen (or at www.optigen.com) and complete and send it to the Baker Institute. How to test your dog Even very young pups can be tested for prcd-PRA. Your veterinarian can collect the small amount of blood needed for the test. No special sampling kit is required since your veterinarian will have the necessary supplies. OptiGen's thorough instructions outline exactly what is needed and give you tips for shipping the sample safely. And finally... As always, an annual eye examination by a board-certified veterinary ophthalmologist is very important since Poodles, like many other dog breeds, can be affected by a variety of inherited and non-inherited eye diseases besides prcd-PRA. Summary - the basic helpful facts This test...
This means... Pattern A result is not limited by the false allele.
You now can...
Please note...
The information on prcd-PRA in OptiGen's brochure and online at www.optigen.com, including the possible occurrence of a false allele and the section of "Frequently Asked Questions", applies to Toy and Miniature Poodles as it does to other breeds with prcd-PRA. Testing can be ordered by using the "Request Test" form and following the "Ship Sample" instructions found online, or by contacting OptiGen at 607-257-0301, email to genetest@optigen.com. Jeanette S. Felix Ph.D., a geneticist, is President and Manager of OptiGen, LLC. Mary M. Woodsen is a freelance writer who specializes is environmental issues, horticulture and canine genetics. |
