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PRA HAS HAD ITS DAY!
Published February 1, 2002
On Feb. 1, OptiGen Laboratory, LLC, a canine genetic testing
laboratory began accepting and processing blood tests to determine - with 99%
accuracy - if your Toller is clear, a carrier of or affected with Progressive
Retinal Atrophy (PRA). This exciting new test, available world wide, is made
available through the research of Dr. Gus Aguirre and colleagues of the James A.
Baker Institute for Animal Health at Cornell University. It was also made
possible by the generous donations of the Van Sloun Fund for Canine Genetics
Research to benefit the work of the Inherited Eye Disease Studies Unit; the
Morris Animal Foundation; The Seeing Eye Inc., Foundation Fighting Blindness;
NEI/NIH grants EY-06855 and 13132, the US and Canadian NSDTR clubs and countless
members and Toller owners.
"The test is as close to perfect as a test can be without
actually being a true gene test," said Dr. Aguirre, Alfred H. Caspary Professor
of Ophthalmology. Technically referred to as the Toller prcd (progressive rod
cone degeneration) test, the new procedure is a gene marker test that can
predict with 99 percent accuracy a Pattern A (clear), Pattern B (carrier) or
Pattern C (affected) Toller. Unlike other prcd tests offered for other breeds,
this marker test is specific for Tollers and results in a greatly reduced chance
(0.05 percent or less) of false positive results. The test eliminates the guess
work from a breeding program with respect to prcd - the only form of PRA seen in
Tollers which results in blindness. Breeders will no longer have to remove
affected and carrier stock from their breeding programs. As long as these dogs
are bred to clear dogs, they will not produce any affected dogs.
The start of the PRA Toller study was first announced in
Quackers (Summer 1994). At that time, founding club members Sue Van Sloun and
Marile Waterstraat met with Dr. Aguirre to outline steps necessary in the quest
for the answer to PRA. By the Fall 1994 issue of Quackers, six Tollers were
featured that were the founding stock for this important research. For the next
eight years, the persistence of Dr. Aguirre, Sue Van Sloun and study
participants helped define the gene marker which is the basis of the new OptiGen
test. Blood samples, fundraising efforts and numerous visits to Dr. Aguirre all
made this test a reality. The entire Toller community will benefit from this
test, and we thank you all for your efforts and contributions.
Here is information to get started:
For PRA study participants:
You need to submit a request form to obtain your test results if any of your
dog's blood samples were sent to Dr. Aguirre for developing this test. Please
understand that all of the submitted samples were not used to develop this test;
therefore, results will not be available for all the research samples from Dr.
Aguirre's lab.
Click here to
download the study participants form in .pdf file format or contact one
of the following people to get a form:
Get Acrobat
Reader for free
To order a prcd Toller blood test:
Detailed instructions are available from
OptiGen's website that explain how to ship a sample, request a test and
information about the Toller prcd test.
For more information Contact:
Sue Van Sloun, Project
Coordinator
(941) 992- 7791 (until 02-15-02)
(508) 636-5386 (after 3-05-02)
Email:Svansloun@aol.com |
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Jane Folkman,
Education/Communication
(508) 339-6916
Email:JaneTolls@aol.com
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Watch this web site for
continuing information about the new PRA test and how to use it.
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Questions and Answers
Q:
What type of PRA (Progressive Retinal Atrophy) is seen in Tollers?
A:
Tollers have the prcd (progressive rod cone degeneration) form of PRA. It is the
only type of PRA known in Tollers at present. Thus, the OptiGen DNA marker test
is expected to identify all cases of Toller PRA in tested animals.
Q:
What is the usual age at diagnosis?
A:
Tollers have been diagnosed with prcd-PRA over a very wide age range - as young
as 3 years and as old as 8 years. The typical age of diagnosis is 4 to 6 years.
As more dogs are examined, it is likely that even younger and older dogs will be
discovered showing first signs of PRA.
Q:
What kind of test is the OptiGen prcd-PRA test for in Tollers”
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 Toller have been chosen. This test is not a
direct mutation or gene test, since the prcd-PRA disease gene in Tollers has not
been discovered yet. Results will be reported as Pattern A (clear), Pattern B
(carrier) or Pattern C (affected), reflecting the pattern of markers in each dog
tested.
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 Tollers. 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 from the initial prcd-PRA test in other breeds where the rate of false
positives was substantial. In Tollers, 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.
Q:
Can you please tell me why both “expressivity” and “penetrance” of prcd-PRA play
an important role in understanding genetic status in Tollers. 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 Toller 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, pedigree, or even the same litter.
One confusing result of reduced or variable expressivity is that a dog can test
Pattern C, affected with 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.
Toller pedigrees with incomplete penetrance have been documented.
Q:
Is there a margin of error for Pattern A?
A:
Pattern A Tollers are statistically normal for prcd-PRA and are not expected to
develop this disease or pass it to offspring. No known Pattern A Toller has
developed PRA or produced PRA-affected offspring, and no known PRA-affected
Toller has tested Pattern A. However, there is a low theoretical chance that a
Pattern A Toller could have a false negative result and therefore be a carrier
(risk is less than 0.5%) or even be affected (risk is less than 0.0025%). False
negative results have not yet been observed with the current test.
Q:
Is there a margin of error for Pattern B?
A:
Pattern B Tollers are not expected to develop PRA and are carriers of 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 PRA-affected instead of a carrier.
Also there is a similar chance (risk if less than 0.5%) of a false positive
result in a Pattern B Toller which would make this dog PRA normal. Neither of
these possibilities (1 out of 200) has been observed yet.
Q:
Is there a margin of error for Pattern C?
A:
Pattern C Tollers are homozygous for prcd-PRA markers and are at high risk for
developing PRA. There is a small theoretical chance, less that 0.5%, of a false
positive result, meaning that a Pattern C Toller 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:
How frequent is prcd-PRA in Tollers?
A:
CERF (Canine Eye Registration Foundation) reports that combined frequency of
PRA-generalized and PRA-suspicious status in Tollers as 7% of 693 dogs with CERF
exam records between 1991-1999. This is a high disease frequency, and might
suggest that a large proportion of dogs at risk for PRA are selected for CERF
exams. If the CERF frequency is valid, it indicates a high rate of carriers in
the Toller populations, possible as high as 40%. However, Dr. Sheryl Krohne,
Diplomate of the American College of Veterinary Ophthalmology says "CERF data
are rough estimates with an incomplete sample reported." A more accurate
prediction of the true incidence of PRA affected, carrier and normal dogs will
become clearer as larger numbers of Tollers are OptiGen tested.
Q:
What Tollers were used in the research to develop the OptiGen prcd-PRA test?
A:
Thirteen families of Tollers, totaling almost 100 dogs, from the US, Canada and
Denmark were studied to develop and validate this test. The test can be used on
purebred Tollers worldwide.
The Eye Committee
Sue Van Sloun
Project Coordinator
Email:Svansloun@aol.com
Sue is a founding member of the Nova Scotia
Duck Tolling Retriever Club in the US. She initiated the PRA study with Dr. Gus
Aguirre, the world's leading expert on PRA, in 1994. Sue has devoted countless
time and resources to solving the mystery of PRA in Tollers. Sue currently
serves as the Project Coordinator for the Eye Committee.
Jane Folkman
Communication/Education
Email:JaneTolls@aol.com
Jane has a BS degree in Animal Sciences from the University of Vermont and a
MS degree in Nutrition from Case Western Reserve University. Jane has previously
served as an Associate Editor and freelance writer for several national health
publications. Jane will provide education articles and communicate information
generated by the Eye Committee.
Liz Corey
Data Coordinator
Email:turkeyridge645@msn.com
Liz has a BS degree in Animal Sciences from the University of Vermont and is
currently working in genetics research at the James A. Baker Institute for
Animal Health in the College of Veterinary Medicine at Cornell University. Liz
will serve as the Data Coordinator for the Eye Committee and provide technical
review for the Eye Committee education articles.
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