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| CONCLUSION
The investigations of this Panel have resulted in the positive detection of the existence of P.R.A. in the Cardigan Corgi. This condition is inherited in a recessive manner, showing no sex or other types of linkage, and hence all untested or genetically unknown Cardigans must be considered as suspect carriers. Since it is not the policy of R.A.S.K.C. to take any steps to control the registration and/or breeding of Cardigans, the responsibility for its arrest and eradication rests squarely on the shoulders of the breeders, and the breeders both collectively and individually must accept this responsibility if P.R.A. is to be eliminated from the breed. If faithfully applied, the test-mating procedures mentioned earlier will lead to the control and eventual eradication of P.R.A., and if put into operation immediately, could result in Australia being the first country which can genuinely claim to have P.R.A. free stock. However, a note of caution must be sounded, for it is possible to fail to detect a carrier occasionally and one must be continually on the alert for its re-appearance. Assuming that adequate breeding records have been kept by each kennel, it should be possible in such cases to detect the carrier animal and hence prevent further incidence of the disease. ACKNOWLEDGEMENTS The Panel wishes to acknowledge the help and guidance it has had during the past twelve months from the following people, and in particular, for the untiring and generous help received from� Mr. R. C. Ratcliffe, B.V.Sc., of the Gladesville Veterinary Clinic, without whose help much of this work could not have been done. Prof. K. C. Barnett, Dept. of Veterinary Clinical Studies, Cambridge University, England. Asst. Prof. J. S. Barker, Animal Husbandry Dept., Sydney University. Asst. Prof. J. Bourke, Physiology Dept., School of Medicine, Sydney University. Mr. J. Keep, Director of Veterinary Clinic, Sydney University. Mr. J. Hodgman, Advisor to Small Animals Centre, Animal Health Trust, England. Mr. R. S. Bowden, Director, Small Animals Centre, Animal Health Trust, England. Mrs. A. Donovan, Research Assistant, Physiology Dept., Medical School, Sydney University. Dr. Cowel, Director, Glaucoma Research Laboratory, Sydney Eye Hospital. Mr. H. P. Manusu, B.V.Sc., Gladesville Veterinary Clinic. Mr. H. Spira, B.V.Sc., Veterinary Surgeon, Member of R.A.S.K.C. Consul. Committee. APPENDIX I The following is the report issued by Dr. K. C. Barnett of Cambridge University following an ophthalmoscopic examination of a 14 weeks old blind puppy which was sent by the Panel to the Small Animals Centre, Animal Health Trust, Kennett, Nr Newmarket, Suffolk, England. The report is dated 3rd May and addressed to Mr. R. S. Bowden, the Director of the Small Animal Centre "Cardigan Corgi Puppy�Male, Red and White" Pupillary reflex present and fair. Conjunctiva clear, cornea clear, normal dark brown iris. Lens�typical arrow head opacities at 12 o'clock, 4 o'clock and 8 o'clock joined along suture line on posterior aspect. Anterior aspect normal. Retina�left eye. Disc pink inside tapetum lucidem, roughly spherical. Vessels narrowed but not an obvious change, and fine ones can be seen on T.L. T.L. green/blue. Increased reflection. No abnormal pigmentation, becoming silvery peripherally. T.N. pale grey/brown, slightly uneven. Retina�right eye. Very similar. T.L. definitely shiny. Again vessels narrowed. But main obvious change to me is reflection. K.C.B. APPENDIX II Extract from Pathology report on the puppy referred to in Appendix I. "Histological Report on Eye Section of Australian Cardigan Corgi Examined at Kennett." Histopathological examination of sections from both eyes reveals a primary retinal atrophy most severe at the periphery, i.e., near ova serrata. There is a degeneration of the rods and cones, and loss of layer organisation just at the periphery, this soon returns to show normal organisation, but still with degeneration of the bacillary layer. There are no changes of the inner retinal layers. There is no evidence of any inflammatory retinitis. There are no changes in the pigment epithelium, and the tapetum and choroid appear normal, as does the optic nerve. Towards the periphery there is some narrowing of the outer nuclear layer. However, the layer of rods and cones is degenerate throughout the eye and this is the only real change. Sections from the other eye show similar changes in the sections examined, but with perhaps more narrowing of the outer nuclear layer. Again the primary changes are in the rods and cones and there is no evidence of an inflammatory retinal atrophy. The changes are again most severe at the periphery. The changes are very similar to those described in the Red Setter some years ago and also similar to those seen in the miniature and toy Poodle and Cocker Spaniel in more recent years; however, the age incidence is obviously much smaller in the Corgi and therefore more similar to the Red Setter than was seen and reported in the Poodle and Cocker Spaniel. 6th September, 1967. (Signed) K.C.B, M.A., Ph.D., S.Sc., M.R.C.V.S. That was then: Now for the present Now it is up to us to keep PRA out of our Cardigans. This should be quite easy as developments in science and technology have made our task simple - have our dogs blood tested - do not breed from a carrier, if such a dog should turn up - do not breed with a dog that has not been proven clear, either by a direct DNA test, by having both parents or the line clear. It is now easy and comparatively inexpensive to have our dogs tested. We should never be faced with the frightening experience of the Cardigan breeders of the 1960�s. That is unless a mutation occurs to give us a different form of the disease. Then, I would hope that we can cooperate to solve this new problem, not lay blame. Hopefully, soon the geneticists will find markers for other problems/diseases plaguing our beautiful dogs and then they will be able to be eradicated, too. I was amazed the other day to find published web pedigrees of current dogs whose parents were carriers of PRA!! The dogs on the pedigree were marked �PRA carrier�. I find this incomprehensible! At least they admitted to using such dogs. We have to be super careful that we import dogs from reputable breeders and make sure they and/or their parents have PRA clear certificates. We also need to keep track of our puppies; make sure that our puppy owners know that they should contact us, if a puppy has a problem. Don�t frighten them by leading them to believe that blindness is likely, but make them comfortable with contacting us with problems. It is possible for another such mutation to occur, but it would not be picked up with our existing test. See following press release. Marker Gene Found for PRA in the Cardigan Welsh Corgi Press Release May 1998 SUBJECT: Identification of the gene mutation that causes progressive retinal atrophy in the Cardigan Welsh Corgi and development of a DNA-based diagnostic test. The gene mutation which causes progressive retinal atrophy (PRA) in Cardigan Welsh Corgis has been identified by Drs. Simon Petersen-Jones and David Sargan at the University of Cambridge in England. PRA in the Cardigan Welsh Corgi is inherited as a recessive defect and causes a progressive loss of vision leading to blindness in the young adult. Following discovery of the gene defect, Drs. Petersen-Jones and Sargan went on to develop a DNA-based test for the PRA-causing gene mutation which can be performed on a small blood sample. This test can be used to identify whether any Cardigan: (1) is a carrier (having one copy of the defective gene and one normal copy of the gene) of the defect; (2) is affected by the defect (having two copies of the defective gene); or (3) is genetically clear of the defect (having the normal version of the PRA causing gene). This test will be pivotal in ensuring that no more Cardigan Welsh corgis affected with this form of PRA are born. Dr Petersen-Jones has recently joined the Department of Small Animal Clinical Sciences at Michigan State University and will shortly be offering the test from there. For details about testing, see below: History of the Development of the Test The first, and most difficult, step in the development of the genetic test was to identify the gene defect that causes PRA in Cardigan Welsh Corgis. Drs. Petersen-Jones and Sargan have for several years been investigating the genetics of PRA in many breeds of dog in an attempt to identify the gene defect in each breed. Along with their co-workers, they had previously been successful in developing the first DNA-based test for PRA. This test was in the Irish Setter breed, which is the only other breed for which the PRA-causing gene defect has been identified. To identify the gene defect in the Cardigan Welsh Corgi, Drs. Petersen-Jones and Sargan initially discovered that a marker they had developed for the gene known as alpha cyclic GMP phosphodiesterase was linked to the PRA defect in affected families from the UK, The Netherlands and the USA. They then sequenced that gene in the PRA-affected corgis and found a mutation in the sequence of the gene, whereby a single one of the some 50,000 bases that makes up the gene (2,583 bases of which code for the protein that the gene produces) was deleted in affected dogs. This very small alteration in the gene has a devastating effect on its function, meaning that the product the abnormal gene codes for is abnormal and much shorter than the normal protein. Dogs which produce this very abnormal gene product in the retina and none of the normal gene product develop a progressive degeneration of the retina known as progressive retinal atrophy. All the PRA-affected Cardigan Welsh corgis that have been investigated have this gene defect, including dogs from affected lines in the USA. To make sure that I understood perfectly where we now stand I put some questions to Dr. Simon Petersen-Jones Here are his answers. Q: How often should we test a line? A: Once both parents are tested and cleared there is no need to test offspring - only will need to test descendents of clear stock again if they are mated with untested or known affected or carrier dog - then test offspring to find status. Q: If this gene could mutate could it do it again? A: Although theoretically possible this is extremely unlikely. The test detects the one nucleotide in the gene that is affected in this form of PRA. The odds of another future mutation causing exactly the same change is very remote. For this reason it is not necessary to test again if you only breed from tested clear animals. Eye testing by a veterinary ophthalmologist is still important in case a different form of PRA arises in the breed. Q: Did our problems arise in the 1960�s from such an abrupt mutation or was the disease in the breed and some unlucky breeding combination brought it to the fore? A: Without DNA samples from the dogs prior to that time I cannot say when the actual mutation arose. It is likely to have been in the background for some time until two carriers were mated and an affected puppy produced, unless a brother sister mating or other very close mating had been performed. Again it is impossible to tell without having DNA samples from back then. So, my interpretation of our responsibilities: - - be careful in our choice of breeding stock - keep an eye on our puppies - check out any suspected problems, first with your vet, to be sure what is causing blindness; there are other causes especially in older dogs - if a problem arises talk to and co-operate with fellow breeders - contact, be guided by and co-operate with the geneticists Then if we are unlucky enough to face another such mutation, we should be able to stop the disease in it�s tracks Getting Our Dogs Tested First check to make sure this is necessary: - - with the register on this site. I have trusted the American CWCA to have checked their information New dogs will only be added if I receive copies of their certificates I have trusted that dogs are true to their official pedigree - with the breeder/owner of your dog or his parents. Both in Australia & New Zealand our dogs can be tested by supplying the appropriate blood sample to: - The Australian Equine Genetics Research Centre (AEGRC), University of Queensland, acting as the agent for OptiGen, LLC, USA, in Australia and New Zealand.� Information can be obtained from their web site - http://omc.uq.edu.au/~ocmps17/?page=29909 To make the process more economical they periodically offer 20/20 clinics. The address of the conveynor for the clinics in each state can be found on this website. One can either register with a clinic and attend a designated "blood draw" - the organisers send the sample to Brisbane or register with a clinic and have your own vet take the sample - you/your vet is responsible for sending and the cost of sending the sample to Brisbane. Gene Technologies, based in Fitzroy, Victoria, now offer the test. They use cheek swabs instead of blood samples. To contact them - pH 3 8412 7077 e-mail [email protected] Web www.gtg.com.au |
| A Little History - Conclusion |
| A Register of Australasian Dogs & Imported Dogs/Semen Tested for PRA |
| A Little History |
| * History cont'd * The Present * Testing |
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| Introduction What is PRA? |
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