Jeanette S. Felix, PhD; Amy Antosh, MS; Becky Iddings
DNA-based genetic testing for canine inherited retinal diseases is a relatively new opportunity. Breeders and owners, with a basic understanding of genetics, can arm themselves with powerful tools for breeding strategies and health evaluations. They can stay up-to-date on the available technology, tests and approaches through internet resources. Many clubs offer breed-specific in-depth materials and/or provide links to informational resources.
OptiGen is a private company organized to access Cornell University biotechnology. Its sole focus is DNA-based veterinary diagnostics, primarily offering tests for canine vision diseases at present. An international market benefits from OptiGen's disease tests, DNA archives, genetic counseling, and research and development. OptiGen maintains an information-dense website to educate and update clients (www.optigen.com).
The first widely available test developed for Irish Setters almost 10 years ago detects the gene mutation for an early onset recessive form of Progressive Retinal Atrophy (PRA). Today, there are mutation and linkage tests for 9 inherited forms of retinal disease among 19 breeds or varieties. Together with genetic tests for other conditions, ranging from rare metabolic diseases to coat color selection, these demonstrate impressive growth in the field of canine genetic testing.
The retinal disease family includes many conditions, both genetic and non-inherited. The list of abnormal eye conditions tracked by CERF (Canine Eye Registration Foundation at Purdue University) demonstrates this variety. OptiGen tests for multiple genetic forms of PRA, as well as Lebers Amaurosis (congenital stationary night blindness--Briards) and cone degeneration (German Shorthaired Pointers). The term PRA is an "umbrella" term covering all inherited diseases that cause progressive degeneration of the retina. However, not all retinal disease is PRA, and not all PRA is caused by the same genetic defect. Also, the inheritance pattern of a retinal disease in a specific breed might be dominant, recessive or X-linked--all modes of inheritance have been seen. OptiGen's tests include 7 types of PRA, each caused by a different gene, with each requiring a specific laboratory test.
One type of PRA, progressive rod cone degeneration or prcd, is the most common. So far, prcd has been identified in 7 breeds as an autosomal recessive condition. The laboratory test for prcd is based on DNA markers that are so closely linked to the disease gene that specific marker combinations predict clear, carrier and affected status with a high degree of accuracy. Development of increasingly informative markers for each breed has resulted in improved prediction ability. The current frequency of the affected status among the 7 breeds ranges from 3-22%, and the carrier status from 28-48%. Clearly, the prcd test is important for prevention of this blinding disease. (to date, breeds with prcd: Australian Cattle Dog, Chesapeake Bay Retriever, English Cocker Spaniel, Labrador Retriever, Miniature and Toy Poodles, Nova Scotia Duck Tolling Retriever, Portuguese Water Dog)
An autosomal dominant form of PRA, present in (Old English) Mastiffs and Bullmastiffs, is detected by testing directly for the disease mutation. Likewise, an X-linked (i.e., on the X chromosome) form of PRA present in Samoyeds and Siberian Huskies, is detected with the exact disease mutation. OptiGen also offers exclusive tests for Type A PRA in Miniature Schnauzers, for a test developed at Swedish University for CLAD (canine leukocyte adhesion deficiency) in Irish Setters and Irish Red and White Setters, and for a test developed at Stanford University for narcolepsy in Dachshunds, Doberman Pinschers and Labrador Retrievers.
New cases of inherited disease can be eliminated in the short-term by identifying clear dogs, free of the mutant disease gene. Based on this straightforward approach, specific breeding recommendations can be given for each mode of disease inheritance. The breeder can use genetic test information to avoid producing affected pups and to control the frequency and occurrence of the mutant gene in their line over the long-term. For autosomal recessive disease, the breeder should always select one parent that has tested clear for the disease in question. The other parent can be untested, carrier, or affected, because the offspring can be tested before planning the next generation. For autosomal dominant disease, the breeder should select only normal male and female dogs, because all dogs with either one or two mutant genes will be affected. For X-linked disease, the breeder should select only normal females, but can select either normal or affected males because no affected offspring will be produced in these breedings.
Several useful conclusions can be drawn from OptiGen's experience with canine genetic testing:
Veterinarians, breeders and owners generally are eager to make use of genetic testing.
Veterinarians are often involved in testing recommendations.
Breed club participation in the processes of test development has been essential.
Internet educational materials are key to teaching and learning more about genetics.
Many breed clubs are playing a central role in educating members about genetics.
Genetic registries and tracking of breed-specific disease frequency enhance test value.
Accurate parentage, pedigree and registration information must be tied to registries.
Breeders and owners need to plan for testing well in advance, not test at the "last minute."
Breeders are willing to submit blood samples for testing, which are considered a reliable source for DNA.
Breeders occasionally need to submit frozen semen as a DNA source for deceased dogs that were key in their line.
Breeders and owners expect reasonable turn-around time for results, and are willing to accept reports by email.
Direct and confidential interaction (phone/email/letter) between the testing agency and client or veterinarian is valued.
Once a test is ready for public use, a commercial testing lab serves client needs reliably and efficiently.