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Cone Rod Dystrophy (crd3) Mutation Test in the Glen of Imaal Terrier

June 16, 2010

Please note cheek swabs are not accepted for this test.

Announcing the crd3 mutation DNA test for Glen of Imaal Terriers: OptiGen is pleased to provide a new DNA test that detects the mutation causing an inherited eye disease, Cone Rod Dystrophy 3 (crd3), in the Glen of Imaal Terrier.

What is crd3? crd3 is one of several cone rod dystrophies that have been recognized in multiple breeds of dogs. All forms of CRD are characterized by the initial loss of cones, the cells in the retina that are responsible for vision in bright light/daylight, followed by the degeneration of rods, the retinal cells that operate during night vision. Unlike another recently identified cone rod dystrophy, crd2, that causes blindness in American Pit Bull Terrier pups by one year of age, crd3 is typically a late-onset disease. Clinical symptoms of crd3 are usually not evident until adulthood has been reached. In some ways, the clinical appearance of crd3 is similar to other common forms of late-onset PRA, namely there is retinal thinning that can be observed by a veterinary ophthalmologist in dogs as young as 3 years of age and retinal degeneration progression, resulting in total blindness within a few years. The Glen of Imaal Terrier’s small population size and its limited gene pool, along with the adult onset of disease -- often after an animal has been bred multiple times-- have resulted in widespread distribution of crd3 within the breed, and many Glens in the general population are likely to be carrying at least one copy of the disease mutation.

What breeds of dog carry crd3? To date, the mutation causing crd3 has been observed in only one breed of dog, the Glen of Imaal Terrier. crd3 is the only form of retinal degeneration that has been recognized in the Glen of Imaal Terrier at this time. It should be noted that many breeds of dog are known to carry multiple forms of inherited retinal disease and the DNA test will not replace the need to remain vigilant for other forms of inherited eye disease in the breed. Regular eye exams should be done in addition to having the crd3 DNA test performed on breeding stock. OptiGen offers Free DNA testing for pedigreed dogs that have been definitively diagnosed as having retinal degeneration, (e.g. PRA or CRD) by a veterinary ophthalmologist. DNA testing of these cases will help us to determine whether any other forms of retinal disease besides crd3 are occurring in the Glen of Imaal Terrier. Owners of PRA-affected Glen of Imaal Terriers are encouraged to contact OptiGen (genetest@optigen.com) to inquire about the Free DNA testing/Research program (http://www.optigen.com/opt9_research.html).

How is crd3 inherited? How should I use the DNA test? As mentioned above, crd3 mutation is widely distributed through the relatively small population of Glen of Imaal Terriers. The abundance of carriers in the population caused initial difficulties in characterizing the mode of inheritance with certainty and it was suspected that the disease had an autosomal dominant mode of inheritance. However once the mutation was identified, it was possible to determine that the disease is inherited in an autosomal recessive fashion, meaning that offspring need to inherit the mutation from each parent (i.e. dogs must have two copies of/be homozygous for the mutation) in order for disease to occur. Carriers of one copy of the mutation (heterozygotes) will not show disease but they can pass the mutation on to their offspring. The great value of the DNA test is that it will allow detection of carriers and pre-symptomatic affected dogs before they are used in a breeding program. In order to avoid producing crd3-affected offspring, carriers of the mutation should never be bred to other cd3-carriers. In other words, at least one of any breeding pair should be homozygous Normal/Clear of crd3 to ensure that no crd3-affected offspring are produced. (See chart below.)

 

Expected results for breeding strategies using the
OptiGen crd3 test
Parent 1
Genotype
Parent 2 Genotype
Normal/Clear Carrier Affected
Normal/Clear All = Normal/Clear 1/2 = Normal/Clear
1/2 = Carrier
All = Carrier
Carrier 1/2 = Normal
1/2 = Carrier
1/4 = Normal/Clear
1/2 = Carrier
1/4 = Affected
1/2 = Carrier
1/2 = Affected
Affected All = Carrier
1/2 = Carrier
1/2 = Affected
All = Affected


This table highlights in yellow the desirable breedings that will NOT produce crd3 -affected pups. These breedings include at least one parent proven "Normal/Clear" by the OptiGen crd3 test. All other breedings are at risk of producing crd3-affected pups.  With the aid of DNA testing, all dogs, even those carrying the crd3 mutation, can be bred with complete confidence that no crd3-affected pups will be produced. It isn't necessary-or even desirable-to remove any dog from the breeding population. Rather, when choosing pups to retain as potential breeding stock, one may select for dogs proven "Normal/Clear" by the OptiGen crd3 test, and select, when possible, against dogs proven to be carriers.  In this way, breeders can retain desirable traits in their lines while moving away from disease. Pups can be tested to distinguish carriers from Normals as soon as they are old enough to have a small blood sample or non-contaminated cheek swab collected.

How do I get my dog’s DNA tested for crd3?To test your dog’s DNA for crd3 please see OptiGen’s Instructions & Information webpage (http://www.optigen.com/opt9_info.html). Complete an order form and send either a cheek swab or whole unclotted blood in EDTA to OptiGen. Tests are typically reported within two weeks of OptiGen’s receiving the sample. Contact genetest@optigen.com with any questions.

Research leading to the discovery of the crd3 mutation was conducted at Cornell University and the University of Pennsylvania, with collaboration by OptiGen.

Reference:

An ADAM9 mutation in canine cone-rod dystrophy 3 establishes homology with human cone-rod dystrophy 9
Orly Goldstein, Jason G. Mezey, Adam R. Boyko, Chuan Gao, Wei Wang, Carlos D. Bustamante, Lynne J. Anguish, Julie Ann Jordan, Susan E. Pearce-Kelling, Gustavo D. Aguirre, Gregory M. Acland.


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Tel: 607 257 0301 · Fax: 607 257 0353 · email: genetest@optigen.com or optigen@clarityconnect.com
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