Graphic: corner
spacer
Graphic: corner
spacer spacer
nav left edge
nav right edge
spacer

Early Onset PRA (EOPRA) Test for Portuguese Water Dogs                 Code 319

Test Pricing

Background:
Another successful collaborative research effort between OptiGen and scientists at the University of Pennsylvania has led to the discovery of a mutation causing Progressive Retinal Atrophy (PRA) in your Portuguese Water Dogs (PWDs). Dr. Keiko Miyadera, Assistant professor of Ophthalmology at the University, has identified this "Early Onset PRA" (EOPRA) mutation in research samples supplied through OptiGen's Free DNA Testing/PRA Research program. Through this program, PWD owners and breeders contacted OptiGen to provide pedigrees, eye exam reports and blood samples from EOPRA affected dogs and their relatives to achieve a critical mass of research material needed for a successful gene hunt. Funding from the Portuguese Water Dog Club of America (PWDCA) provided major support for the research, both in its initial phase as well as through funding of the whole genome sequencing steps that were critical to the mutation's discovery. In addition to the PWDCA, OptiGen and the university researchers would like to express our sincere appreciation for the dedicated efforts of members of the PWDCA who enabled the collection of the research samples. Without their hard work in contacting owners and assisting in procuring samples, pedigrees and eye exam information, none of this work would have been possible.

PWD breeders are perhaps one of the most well aware groups of people when it comes to Progressive Retinal Atrophy, thanks to the historic prevalence of another form of PRA - progressive rod cone degeneration (prcd) -- in the breed. The PWDCA's education outreach on prcd-PRA serves as a shining example of how successful a breed club can be in improving a breed's health through making members aware of inherited disease as well as supporting basic research to allow a DNA test to be developed that will allow breeders to assure that no affected puppies are produced. OptiGen and the research team at Cornell University led by Drs. Gus Aguirre and Greg Acland worked closely with the PWDCA in the hunt for the prcd mutation through the late 90s and early 2000's. At that time, the prevalence of the prcd form of PRA in the breed was distressingly high and due to the relatively late onset of clinical signs of this form of PRA, carriers of the mutation were not obvious until after multiple litters had been produced. DNA testing for prcd offered the breed an essential means of avoiding the disease while still protecting valuable blood lines and likely helped save the breed from serious decline.

Fortunately for the breed, the EOPRA is not nearly as common as prcd --- possibly due in part to its comparably much earlier expression of clinical signs. It is not yet known what the frequency of the EOPRA mutation is in the general PWD population however as DNA testing becomes available, this information will become evident and OptiGen will openly share it with the PWD community. EOPRA has typically been diagnosed by veterinary ophthalmologists during routine eye exams when PWDs are younger than 4 years of age, however the slowly progressive change in vision may not be obvious in some cases. Both prcd and EOPRA share standard PRA clinical expression, e.g. initial hyper-reflectivity of the fundus (back of the eye) due to the thinning retina as photoreceptor cells die, followed by attenuation of blood vessels that feed the retina. Eventually, as more of the photoreceptors die, the affected dogs become completely blind. The main obvious difference between the two diseases is the age of which retinal degeneration becomes evident.

Early Onset PRA Cases that are not due to the newly identified EOPRA mutation:
We are, at this point, aware of three anomalous cases of PRA in the Portuguese Water Dog. All three dogs have shown signs of progressive retinal degeneration starting at an early age (less than ~2 years) but none of them carry the newly identified EOPRA mutation. Interestingly, two of these cases are also homozygous for the prcd mutation. We know that there are modifiers of prcd-PRA that can affect the ages of onset of clinical signs in some breeds of dog. Possibly there are modifiers of prcd that can accelerate the effects of the mutation and result in a much earlier expression of disease than is typical for prcd and that could explain two of the three cases.  But the possibility also exists that there is another, as yet uncharacterized, mutation causing Early Onset PRA in the Portuguese Water Dog. This would not be terribly surprising as many breeds of dog are known to carry multiple PRA-causing mutations. For this and other reasons, OptiGen stresses the reminder that DNA tests, although incredibly useful, in no way replace the importance of regular eye exams by a board certified veterinary ophthalmologist.

EOPRA mutation based test:
A DNA-based test has been developed to target the mutation responsible for Early Onset PRA (EOPRA) in the Portuguese Water Dog. The EOPRA test can be used to determine the genetic status of a dog in respect to the mutation and to make informed decisions about mating options to prevent the occurrence of this undesirable blinding disorder in progeny.

The DNA-based EOPRA test allows genotype determination of a tested dog as being:

NORMAL - the dog has two copies of the normal gene and it is not going to develop Early Onset PRA caused by the EOPRA mutation.

CARRIER - the dog has one copy of the normal gene and one copy of the EOPRA mutation. The dog will not develop clinical signs of Early Onset PRA due to the EOPRA mutation but it will transmit one of the EOPRA mutation to about 50% of its progeny.

AFFECTED - the dog has two copies of the EOPRA mutation and is expected to develop/is already showing symptoms of the Progressive Retinal Degeneration caused by the EOPRA mutation.

Testing and Breeding Recommendations:

Expected results for breeding strategies using the
EOPRA 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

By selecting the mate with the appropriate genotype, it is possible to breed affected or carrier dogs and never produce affected progeny. In this manner the genetic diversity of the breed can be maintained.

 

 



spacer
Graphic: footer bar left
OptiGen®, LLC · Cornell Business & Technology Park · 767 Warren Road, Suite 300 · Ithaca, New York 14850
Tel: 607 257 0301 · Fax: 607 257 0353 · email: genetest@optigen.com or optigen@clarityconnect.com
Graphic: footer bar right
spacer spacer
spacer
spacer
spacer