As many of you have heard, OptiGen intends to announce the completed test for prcd-PRA in Australian Cattle Dogs on May 1, 2002. There are many questions being asked about this test, the following are the most common questions that we're hearing. Please understand that these answers have been complied from information on the optigen website and from private emails. They are correct to the best of our knowledge, but as with everything they are subject to change without notice. OptiGen can obviously not be held to any of the information we're presenting on this page. For questions that are not answered on this site, please visit OptiGen for more information. We're still waiting on Dr Acland to do a final proof of this page and information may be changed or updated after he looks in. If you see an inaccuracy within this page, contact genetics committee chair Joyce Rowland at Olliame@aol.com.

Q: When will OptiGen start accepting blood samples?
A: As far as we know, OptiGen will start accepting blood samples for testing after May 1, 2002. If there is any change of plans this page will be updated with new information.

Q: How much will it cost?
A: Testing will be $260 per individual dogs. There are discount plans for litters of puppies that are less than 12 weeks old; these puppies will be tested for $200 each. Additionally, there is a "20/20" plan, groups wishing to gather 20 dogs for testing will be able to get a 20% discount per dog. This works out to $208 per dog.

Q: How do I request the test?
A: On the OptiGen website (www.optigen.com) there will be a downloadable form for the test. You will fill out the form and follow directions on how to send blood to OptiGen. Reporting will take about two weeks after receipt.

Q: How can I get results if I sent in blood for the initial research study?
A: Many individuals have assisted in the research study by providing blood samples from dogs. Some samples were used in developing the DNA-based test now used to establish the genetic status of dogs. In other cases, the samples were either not used, or not tested definitively, because the dogs were not informative for disease status, or because definitive testing of these samples was not necessary for developing the test. If you would like to receive information concerning samples you submitted, please download the form in either .doc format or .pdf format and follow the instructions within to request your results. Please allow several months for a response.

Q: How accurate is the test?
A: (as taken from the OptiGen website with modifications still under review by) Reliable identification of dogs that do not carry disease genes is the key to eliminating autosomal recessive diseases, like prcd-PRA. The OptiGen prcd-PRA test for Australian Cattle Dogs provides almost 100% identification of these dogs. Called "genetically clear", "noncarriers" or, more formally, "homozygous normals," such dogs pass the normal gene on to all their pups with a very high probability - which means that their pups have a very low risk of being affected with prcd. These "clear" dogs can be bred to any mate - even to a prcd-affected dog that may be a desirable breeding prospect for other reasons.

Homozygous means both copies of the gene in your dog are the SAME - both normal or both prcd. A carrier has one normal and one prcd gene.

The OptiGen prcd test is a marker test rather than a mutation-based gene test. This means that it identifies dogs by a "fingerprint" on chromosome 9 near the prcd gene locus, rather than by detecting the prcd mutation itself. The result of the test is a genotype or pattern - a fingerprint - that allows the separation of dogs into three groups: pattern/genotypes A, B and C. Due to the properties of the Australian Cattle Dog markers, there is a low risk of recombination - or dissociation - between these markers and the prcd gene. Therefore, this marker test classifies Australian Cattle Dogs into three risk groups as shown in this Table.

The next table shows that all the desirable breedings include at least one parent with Pattern A genotype from the OptiGen prcd test. All other breedings are at risk of producing pups of Pattern C, with a high probability of developing prcd. However, all dogs can be bred with a high degree of safety. It isn't necessary - or even desirable - to remove dogs from the breeding population. But when choosing pups to retain as potential breeding stock, it is important to select for dogs with Pattern A genotype - and select against dogs with Pattern C genotype.

The OptiGen prcd test can be done reliably at any age, and the test result will never change with age. Since Australian Cattle Dogs are affected with other eye diseases, we recommend that yearly eye examinations by a board certified veterinary ophthalmologist be continued, for example, through the CERF program in the U.S. or similar program elsewhere. A normal exam in a young dog cannot rule out prcd-PRA.

Q: What kind of test is the OptiGen prcd-PRA test for Australian Cattle Dogs?
A: The test is a DNA marker test, where markers very close to the disease gene are used to predict the associated normal or affected allele. New markers that are specifically informative for the Australian Cattle Dog have been chosen. The test is not a direct mutation test, since the prcd disease gene has not been discovered as yet. Results will be reported as Pattern A, B or C, reflecting the pattern of markers in each dog. See sample reports.

Q: Are there any proven cases of false negatives in this test?
A: Two dogs out of 250 did not show as ³Affected² (Pattern C) using the prcd-PRA test for Australian Cattle Dogs--even though they appeared to have PRA upon exam by Dr. Acland. Upon further pedigree research it is believed that these dogs do not have prcd-PRA. If this is accurate, they are not false negatives for prcd. Rather they are ³positive² for another disorder and do not have prcd-PRA. They may have another, rare form of PRA or an acquired retinal degenerative disorder. OptiGen has agreed to do follow up work on any ACD¹s that do not test as Affected but subsequently are diagnosed with PRA.

Q: Are there any proven cases of false positive alleles in this test similar to other breeds?
A: So far there is no known case of a false positive allele in Australian Cattle Dogs. There is no evidence so far that a Pattern B dog might actually be Pattern A, nor that a Pattern C dog might actually be Pattern B or even A. This situation is very different than for the initial prcd-PRA test in most other breeds where the rate of false positives was substantial. In Australian Cattle Dogs, the risk of a false positive result is estimated to be less than 0.05%, based on the theoretical possibility of recombination between the prcd gene and the prcd markers. With more extensive testing of new pedigrees, it is possible that the issue of false positives in Pattern B or C might need to be reconsidered

In Australian Cattle Dogs, both “expressivity” and “penetrance” of prcd-PRA play an important role in understanding prcd-PRA genetic status.

Q: What is variable expressivity?
A: Some diseases are very predictable in terms of age of onset and severity of symptoms. Such a disease is typically “expressed” in the same way in each affected individual. But Australian Cattle Dog prcd-PRA doesn’t fit this description. It can have different ages of onset, different degrees of severity, and/or different rates of progression within the same line, the same pedigree, or even the same litter. One confusing result of reduced or variable expressivity is that a dog can test Pattern C, affected with prcd-PRA, yet show no clinical signs of abnormal vision until much later, or show only mild and slowly progressing clinical signs of the disease. This dog must not be confused with a case of false positive.

Q: What is penetrance?
A: The extreme case of reduced expressivity is incomplete penetrance. An inherited disease has incomplete penetrance in cases where the individual is known to have the affected genotype, but never shows the disease. Even so, the clinical disease shows up again in its offspring. Clearly, the affected genes were present in the parent but the disease didn’t “penetrate” to a recognizable state. Again, this case must not be confused with a case of false positive. Australian Cattle Dog pedigrees with incomplete penetrance have been documented.

Q: Is there a margin of error for Pattern A?
A: Pattern A Australian Cattle Dogs are statistically normal for prcd-PRA and are not expected to develop this disease or pass it to offspring. Of particular note for ACD's is Dr. Acland's observation that, although prcd-PRA is the predominant form of prcd-PRA in ACDs, there might be a second form of prcd-PRA in ACDs, since 2 affected ACDs were not detected with this marker-based test (see above answer on false negatives). 

Q: Is there a margin of error for Pattern B?
A: Pattern B Australian Cattle Dogs are not expected to develop prcd-PRA and are a carriers of prcd-PRA with at least 99% certainty. There is a chance (risk is less than 0.5%) of a false negative result, which would make this dog prcd-PRA-affected instead of a carrier. Additionally, there is a similar chance (risk is less than 0.5%) of a false positive result in a Pattern B Australian Cattle Dog, which would make this dog prcd-PRA-normal. Neither of these possibilities has been observed as yet.

Q: Is there a margin of error for Pattern C?
A: Pattern C Australian Cattle Dogs are homozygous for prcd-PRA markers and are at high risk for developing prcd-PRA. There is a small theoretical chance, less than 0.5%, of a false positive result, meaning that a Pattern C Australian Cattle Dog could be a carrier, or with even lower chance, less than 0.0025%, could be normal. False positive results have not yet been observed with the current test.

Q: What information will be given on my test report?

A:

1. If the result is Pattern A, the report will read:

   Test Results: Pattern/Genotype A

   Risk Group: Normal

   Risk for developing prcd form of prcd-PRA: Pattern A Australian Cattle Dogs are statistically normal for prcd-PRA and are expected not to develop this disease or pass it to offspring. No known Pattern A Australian Cattle Dog has developed prcd-PRA or produced prcd-PRA-affected offspring, and no known prcd-PRA-affected Australian Cattle Dog has tested Pattern A. There is a low theoretical chance that a Pattern A Australian Cattle Dog could have a false negative result and therefore be a carrier or even be affected.

   Significance for breeding: Pattern A Australian Cattle Dogs can be bred to any dog and, with at least 99.5% confidence, will not produce pups affected by the prcd form of prcd-PRA.
   
   

2. If the result is Pattern B, the report will read:

   Test Results: Pattern/Genotype B

   Risk Group: Non-affected

   Risk for developing prcd form of prcd-PRA: Pattern B Australian Cattle Dogs are expected not to develop the prcd-PRA, and are carriers of prcd-PRA, with at least 99% certainty. However, as for the Pattern A result, there is a small chance of a false negative result, which would make this dog prcd-PRA-affected instead of a carrier. Additionally, there is a similar chance of a false positive result in a Pattern B Australian Cattle Dog, which would make this dog prcd-PRA-normal. Neither of these possibilities has yet been observed with the current OptiGen test.

   Significance for breeding: Pattern B Australian Cattle Dogs have a high probability of being a carrier of prcd-PRA and a very low probability of being affected. They should only be bred to Pattern/Genotype A mates in order to greatly reduce the chance of producing affected pups.
   
   

3. If the result is Pattern C, the report will read:

   Test Results: Pattern/Genotype C

   Risk Group: High Risk

   Risk for developing prcd form of prcd-PRA. Pattern C Australian Cattle Dogs are homozygous for prcd-PRA markers and are at high risk for developing prcd-PRA. There is a small theoretical chance, less than 0.5%, of a false positive result, meaning that a Pattern C Australian Cattle Dog could be a carrier, or with even lower chance, less than 0.0025%, could be normal. False positive results have not yet been observed with the current OptiGen test. Except for this theoretical possibility, all Pattern C Australian Cattle Dogs will eventually develop prcd-PRA if they live long enough. Known cases of extremely late onset of prcd-PRA indicate that some Pattern C Australian Cattle Dogs might not be diagnosed with prcd-PRA during their lifetime.

   Significance for breeding: Pattern C Australian Cattle Dogs should only be bred to Pattern/Genotype A mates in order to greatly reduce the chance of producing affected pups.

In addition, he notes that onset of prcd-PRA in ACD's can be quite late in life, and a dog cannot be considered free of prcd-PRA until at least 8 years of age with a clear eye exam. 

Finally, he suggests that, since he suspects a high carrier rate, owners should choose to test key dogs in the lines first.

Q: What is the role of the Orthopedic Foundation for Animals (OFA) in the prcd-PRA test?
A: At the request of the ACDCA Board, the OFA has agreed to serve as database administrator for the Australian Cattle Dog Health Registry. This Registry will include information not only on hips and elbows (what OFA is best known for) but also BAER test results, cardiac test results, thyroid and many other health conditions. Because of their extensive background in canine health registration and reporting, OFA was a logical choice to maintain the database for prcd-PRA. They will also provide this service for other disorders that we designate. You can retrieve information on certain results by calling OFA or using their Internet site www.offa.org.

Q: How will OFA obtain the information on prcd-PRA results?
A: OptiGen will send OFA a monthly report of results on all U.S. owned Australian Cattle Dogs that have been tested. The report will include the usual information required by OFA-name of dog, registration number, date of birth, etc.

Q: Who authorizes the release of information to the OFA?
A: The owner of each U.S. owned dog must agree to permit release of the information to the OFA. If the owner does not agree, OptiGen will not perform the test.

Q: What results will OFA have on dogs that have been tested for prcd-PRA?
A: For statistical purposes OFA will have information on all U.S. owned dogs. For reporting to the public, OFA will release the identify of all dogs testing Pattern A/Normal through their website or over the phone.

Q: What about the release of information on Pattern B and C dogs?
A: OFA will also contact the owners of all Pattern B and Pattern C dogs and request written permission to release their results.

Q: I have heard that the ACDCA membership will have an advisory vote on whether to ask OptiGen to change how these results are reported. Is this true?
A: This is true. The time frame is yet to be determined but hopefully no later than May 1.

Q: Does the requirement to report information to OFA apply to non-U.S. owned dogs?
A: No. OptiGen relies on the parent club of the breed in each country to advise on protocols for reporting results. Arrangements for voluntary submissions have not yet been established, although there undoubtedly will be an approach for handling these.

Q: Is there a cost for registering this information with OFA?
A: The normal cost is $15 per dog or $30 dollars for a litter of three or more. However, a donation has been made to OFA by an ACDCA member that will cover registration costs for the first 200 Australian Cattle Dogs.