Jeanette S. Felix, PhD and the staff at OptiGen, LLC
Opportunities to benefit from DNA-based genetic testing for canine inherited diseases are increasing steadily. Breeders and owners, with a basic understanding of genetics, can use these powerful tools for enhanced 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 specializes in tests for inherited forms of eye disease, currently with 10 tests used, in total, for 29 breeds/varieties. Together with genetic tests for other conditions, ranging from rare metabolic diseases like ceroid lipofuscinosis to coat color selection, these demonstrate growth in the field of canine genetic testing. In 2005, OptiGen announced two advances: a mutation test for CEA and, replacing the previous marker test, a mutation test for prcd-PRA.
CEA - Collie Eye Anomaly, also known as Choroidal Hypoplasia, is an autosomal recessive disease in the Border Collie, Rough and Smooth Collie, Australian Shepherd, Shetland Sheepdog, and Lancashire Heeler. With this condition, the choroid layer at the back of the eye does not develop normally, so the primary abnormality can be diagnosed clinically at a very young age. There is a huge range in severity of the disease, from extremely mild with no consequences to vision, to total blindness in a small percentage of cases. The mutation frequency is especially high in Rough and Smooth Collies.
The retinal disease family includes many conditions, both genetic and non-inherited. The list of eye conditions tracked by CERF (Canine Eye Registration Foundation) demonstrates this variety. OptiGen tests for Lebers Amaurosis (congenital stationary night blindness - Briards) and cone degeneration (German Shorthaired Pointers), as well as for multiple genetic forms of Progressive Retinal Atrophy. 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. The inheritance pattern of a retinal disease in a specific breed might be dominant, recessive or X-linked - all modes of inheritance have been documented. OptiGen's tests include 7 types of PRA, each caused by a different gene, with each requiring a specific laboratory test.
The most prevalent type of PRA, progressive rod cone degeneration or prcd, has been identified in 13 breeds/varieties as an autosomal recessive condition. With a test based on the disease-causing mutation, a dog's status of Normal/Clear, Carrier or Affected can be determined with the highest degree of accuracy available in genetic testing. The current frequency of affected status 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, these breeds have prcd: Amer. Cocker Spaniel, Amer. Eskimo, Aust. Cattle Dog, Aust. Stumpy Tail Cattle Dog, Chesapeake Bay Retriever, Chinese Crested, English Cocker Spaniel, Entlebucher, Labrador Retriever, Miniature and Toy Poodle, Nova Scotia Duck Tolling Retriever, and Portuguese Water Dog.
Other types of PRA can be diagnosed by direct detection of mutations: recessive early onset PRA in the Irish Setter and Sloughi; autosomal dominant PRA in the (Old English) Mastiff and Bullmastiff; X-linked (i.e., on the X chromosome) PRA in the Samoyed and Siberian Huskie; and Type A PRA in the Miniature Schnauzer.
Recently, OptiGen licensed the DNA-based test for the Border Collie neuronal ceroid lipofuscinosis disease, referred to as CL. This recessive gene defect is identified in lines of Australian descent, with up to 3% Carriers. CL results in accumulation of lysosomal storage bodies, leading to progressive degeneration of brain and eye cells with severe neurological impairment and early death. Affected dogs exhibit symptoms early in life - around 1- 2 years.
OptiGen also exclusively offers the test for CLAD (canine leukocyte adhesion deficiency) in the Irish Setter and the Irish Red and White Setter, and a test for narcolepsy in the Dachshund, Doberman Pinscher and Labrador Retriever.
The breeder can use genetic test information to immediately avoid producing affected pups and to control the frequency and occurrence of the mutant gene in their lines over the long-term. For autosomal recessive disease, the breeder should always select one parent that tests clear. 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 males and females, 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 and breeders/owners generally are eager to make use of genetic testing.
Veterinarians often are involved in testing recommendations.
Clients expect to access information and genetic counseling through the testing lab
Direct, confidential interaction with the testing lab is valued.
Internet educational materials are key to teaching and learning more about genetics.
Many breed clubs play a central role in educating members about genetics.
Breed club participation in the processes of test implementation has been essential.
Genetic registries and tracking of breed-specific disease frequency enhance test value.
Accurate parentage, pedigree and registration information must be tied to registries.
Breeders/owners need to plan for testing well in advance, not test at the "last minute".
A commercial testing lab serves client needs most reliably and efficiently.
OptiGen is a private company originally organized to access Cornell University biotechnology. Its sole focus is DNA-based veterinary diagnostics with test offerings for a growing list of canine vision diseases. An international market accesses OptiGen's 16 disease tests for 39 breeds/varieties, DNA archives, individualized genetic counseling, and research and development. OptiGen maintains an information-dense website to educate and update clients (www.optigen.com).