Bob Jackson submits this article.
With kind permission from the writer Eugene Phoa for the fanciers of The English springer spaniel. Published with kind permission of the author.
While the thoughts expressed in this Article are mine and I must therefore take the blame for any mistakes made, they have been developed in consultation and conversation with a number of well-established breeders both within and outside North America. These breeders are concerned with the view, stridently expressed by some, that Optigen A status is an essential part of responsible breeding. This is a view which I believe arises out of a misunderstanding of the place. Such tests should take in a breeding program and a blind acceptance of the value of such tests.
As many of you know, at the General Meeting of the ECSCA which was held some years ago and at which questions were raised such as the mandatory publication of the results obtained by Optigen in tests carried out on members’ EC’s, I urged that we proceed with a degree of caution. That was a viewpoint which arose from my experience as a solicitor that, all too often, products are rushed into the market by commercial ventures, it being well established commercial reality that there is a tremendous advantage to be first in the market with a product, and that, not infrequently, this “rush to the market” approach results in the marketing of a product which is less than reliable. I expressed that viewpoint purely as a general view on new commercial products and without any particular reference to Optigen or its product.
In the time that has passed since that general meeting of the ECSCA, a number of dogs have been tested by Optigen and duly classified as “A” (completely clear), “B” (carriers) or “C” (afflicted). One very worrying matter was the apparent lack of correlation between Optigen C’s and (based on anecdotal evidence) clinically blind dogs, especially in solids. Because of this, I (and, I believe, several others) awaited the publication by Optigen, of the research on which its tests were based, in the belief that if that research was published in a publication of good repute, it could be peer reviewed by scientists qualified so to do. What happened a few years later was Optigen’s offer to re-test animals which they had previously tested and classified. Those re-tests resulted, at least in some cases, in animals being completely re-classified so that, again in some cases, EC’s classified as C’s (i.e., afflicted) came back on re-testing as A-1’s (completely clear). What was the reason for this change? At very least, it was an admission by Optigen that it’s earlier tests were less than reliable. Then, fairly recently, the ECSCA web-site contained a press release purportedly by Optigen, in which it was claimed that the actual gene for prcd/PRA had been identified, rendering even more important the validation of the Optigen test by the all-important peer review process; however, as of the time of the preparation of this article, Optigen has not published its research. This has led to more unease on the part of a not inconsiderable number of breeders with whom I have spoken, on whether they should or should not have their dogs tested.
There is, of course, always the question of the costs involved (and who in the business of breeding and showing dogs these days is unaware of the costs)! But perhaps more significant is the question of how much importance one should attach to the results of such tests. There was the “flare up” which, I believe first focused breeders’ attention on prcd/PRA in the early to mid ‘Sixties, when one or more dogs in the United Kingdom, including Mrs. Doreen Robertson’s beautiful blue Nostrebor Neopolitan, were withdrawn from public stud because of the problem, after which the problem seemed to “fade away”; there was the rise in the late ‘Eighties in North America, when another “wave” of clinical prcd/PRA seemed to erupt, and that also seemed to fade away. Apart from these “peaks”, although prcd/PRA has been with us, it does not seem to have been a significant problem in our breed. Also, we have some time now, had the benefit of the expertise of veterinary ophthalmologists, and of ERG’s, methods which have served us well in detecting the few cases of the problem in our breed.
I do not know of any facts which indicate that the incidence of prcd/PRA in our breed, has since changed. Recent enquiries to several leading breeders – some of partis and some of solids – would appear to indicate that the incidence of clinical prcd/PRA is still small. Even breeders who have been in the game for many years and have over that time bred goodly numbers (in the region of several hundred), have indicated that, to the best of their knowledge, they have had, if any, a single or perhaps two or 3 dogs which have gone blind with what was diagnosed as clinical prcd/PRA. Admittedly, these breeders have not been able to follow every pup they have bred, but I submit that it is a reasonable expectation that if a significant number of the stock sold had gone blind, at least SOME the purchasers would have complained. This brings me to my first (and perhaps most important) point. What is new is not a rise in the incidence of prcd/PRA, but only a new, and perhaps more accurate method of examining our EC’s for the same. THE BREED IS NOT FACING A CRISIS, and I would urge all breeders not to act precipitously. Although prcd/PRA is clearly something of which we should be aware and avoid if possible, it is not to be compared with, say, Familiar Nephropathy (“FN”) which is a fatal condition and in which, so I am informed, the animal would die in great distress unless put down.
In June, 2005, an announcement was made that Optigen had now located the actual gene responsible for prcd/PRA. This claim could only have substance if it applied to the whole of the breed, i.e. that this particular gene was responsible for prcd/PRA in both solids and partis. There was, however, a difficulty: if this gene is responsible for the condition in all EC’s, then how was one to explain the fact that in one subgroup (partis) the condition expressed itself early (2-4 years), whereas in another subgroup (solids) of EC’s carrying the same relevant gene structure, the expression was very different in that its was late (7-8 years) and its members in some cases, died as sighted dogs, i.e., never exhibited clinical signs of prcd/PRA. As I understand Optigen’s statement, they attribute this difference, i.e., the difference in the manifestation of clinical prcd/PRA in the two groups, to the presence, in one group, of another gene (which, for the sake of convenience, I will term “the Interfering Gene”). To quote the Optigen press release of June 1 2005 (as it appears in the ECSCA web page):
“We have also retested the pedigrees of extremely late onset PRA, that had multiple members testing as Pattern C1. All of the C1 dogs are “Affected” with the mutation test. That leaves us with the theory that this subgroup inherits prcd-PRA but also must inherit an unidentified second gene that modifies the onset of PRA, causing some “Affecteds” in the pedigree to exhibit typical prcd-PRA, and some retain good vision throughout their lifetime. Unfortunately, we do not have any more satisfying explanation for the situation. Hopefully it will be more clear with ongoing research.”
Although Optigen does not identify the two groups as partis and solids, I believe that, generally speaking, the experience of most of us is that the two groups or subgroups are indeed partis and solids, and for ease of reference, that is how I propose to refer to them in this article. If the number of cases of the condition in partis can fairly be characterized as being small, it has, in solids through all this time, been minimal. Certainly my own experience as a breeder of (mainly) solids, confirms this: as have many breeders, I have, over the years, frequently had my dogs’ eyes examined by qualified veterinary ophthalmologists. I can only recall having one blind EC in my stock, over what is now over 45 years in the breed, and his condition was professionally diagnosed as being the result of diabetic cataracts. This difference in expression of the condition in partis and solids, has been a puzzling factor, because both partis and solids come from the same root stock - the practice of breeding partis only to partis and solids only to solids, is a fairly recent innovation – and one would not, therefore, expect a different genetic makeup in coloured dogs as compared to solids. If one goes back to the ‘Fifties and even more in the “Forties, what we nowadays term “cross-colour breeding” was not at all uncommon.
There are several possible explanations for the difference in the clinical manifestation of prcd/PRA in partis and solids, including the following:
Let us assume, however, that Optigen’s hypothesis is correct – that there is an Interfering Gene in solids. How does one explain the fact that a good number (if not most) solids which test as Optigen C‘s, remain sighted throughout their lifetime? One explanation that has been related to me, is that if those dogs lived long enough, they would indeed go blind! This is obviously something incapable of being proven right or wrong, and is therefore more properly consigned to the realm of speculation. “Explanations” of this type are, to my mind, completely detached from the reality which we, as breeders, have to deal with, and as such, are without value. In any event, all living systems suffer the ravages of time, and if the retina (or any other part, for that matter) of an EC of 12 or 13 years of age starts to deteriorate, that is not something which, I suggest, should be unexpected.I would also question the actual predictive value of the test for Optigen C classified dogs, i.e., how many C classified dogs have in fact developed the condition within their normal life span and what proportion of C classified dogs can we confidently predict will develop the condition? I have seen no statistics on this point, but clearly (as Optigen appears to agree) there are a number of cases where C classified dogs do NOT develop the condition, and more research needs to be on this point before the value of the Optigen test can be properly established..
There are additional questions. Is it possible that, in many situations in which an EC passes on the prcd/PRA gene, it also passes on the Interfering Gene (i.e., that in those EC’s, these two genes sort of go in tandem, that there is some sort of “linkage” here )? If the Interfering Gene is often linked with the prcd/PRA gene, this would clearly diminish the significance of the prcd/PRA gene (and the corresponding Optigen C classification) in a breeding program.
I also question the wisdom of proceeding headlong into this field of the testing offered by Optigen, on the basis of the present science. If Optigen is correct and an Interfering Gene exists, or if the expression of the prcd/PRA gene is somehow dependant on some other factor, such as linkage, or the augmenting action of the R and T genes mentioned above, then, by definition, prcd/PRA is polygenic in origin, and not a simple autosomal recessive. Conditions which are polygenic in origin, are problematical. In the publication “Reproduction in Domestic Animals, Vo. 38, issue 1, page 73 – February 2003, headed “Ethics and Genetic Selection in Purebred Dogs”, V.N. Meyers-Wellen states:
“When we understand polygenic inheritance, we can potentially eliminate whole groups of deleterious genes from populations …. however, until we have enough information on gene interaction, we will not know whether some of these genes have other functions that we wish to retain. And, other population affects should not be ignored. At least initially it may be best to use this new genetic information to avoid mating combinations that we know will produce affected animals, rather than to eliminate whole groups of genes from a population. This is particularly important for breeds with small gene pools, where it is difficult to maintain genetic diversity.
Finally, we will have enough information about canine gene function to select for specific genes encoding desirable traits and increase their frequencies in a population. This is similar to breeding practices that have been applied to animals for hundreds of years …. This has great potential to improve the health of the dog population as a whole. However, if we or our breeder clients make an error, we can inadvertently cause harm through massive, rapid selection. Therefore, we should probably not be advising clients on polygenic traits or recommend large scale changes in gene frequencies in populations until much more knowledge of gene interaction is obtained.”
I feel that the above advice is something we all should heed. It is certainly axiomatic that we should certainly avoid combinations which we know will produce blind animals – and I believe that every responsible breeder of EC’s does that - but we should not be rushing headlong into a situation which could have undesirable results for our breed as a whole.
The primary aim of a good EC breeder, MUST be to breed good EC’s. Many are the factors which go into the selection of stud dogs and brood bitches. Even assuming 100% accuracy, the Optigen tests are only determinative for a single (out of many) factors which should be considered. It is to be remembered that all Optigen claims to do, is to be able to identify the gene responsible for prcd/PRA. It would be completely incorrect, and unfair to Optigen, to read any Optigen result as doing anything more than that. Even just considering the eye (and what about the rest of the dog!), there are many other parts of the eye which could be subject to one or more genetic defects. It is fairly well established that in dogs, senile changes and degradation in the eye starts at about 7 years. Of what use is a perfect retina if the function of the eye degrades by reason of, for instance, changes in the anterior chamber?
On a related point: in 1998, Dr. David Huntsman of the British Columbia Cancer Agency identified a gene (the E–Cadherin gene) in a certain family. In its normal function, this gene produces the “glue” which holds cells together. The mutated gene, however, also causes stomach cancer. Obviously, one couldn’t just try to get rid of the gene (otherwise the patient’s cells would just fall apart), and the only recourse in the case of persons carrying the mutated gene, was prophylactic surgical removal of the stomach. As Meyers-Wellen has stated, genes sometimes have more than one function, and until we know for sure ALL of the functions of that gene, it is dangerous to breed to eliminate it. Obviously, if the gene which, in its mutated form produces prcd/PRA in EC’s, also performs some desirable function, that desirable function could not be one which is central to the maintenance of life (as is the case in the E-Cadherin gene), but it is theoretically possible that it performs some desirable but less essential function. However, Meyers-Wellen’s advice quoted advice still applies.
There is a place for genetic testing in dog breeding, but I believe that all tests must, before widespread application in a breeding program, be subject to close scrutiny, and, until they have passed that test, must be approached with a degree of caution. Even after passing that test, they should only be used sensibly. In particular, the general advice not to “throw the baby out with the bathwater” ALWAYS applies except, of course, in the case of fatal inherited conditions such as FN. I repeat that our objective, as breeders of EC’s, must always be to breed better EC’s, and a genetic problem with one aspect or another of any particular animal – whether of hips, eyes, or anything else - or family of animals, must always be considered in the context of that pre-eminent objective of a good breeder, which is to breed better English Cockers. A sound retina is only ONE feature. A mongrel with sound retinas does not a Cocker make. No single feature should be elevated above the general requirements of our wonderful breed – a short, compact, sound moving, happy little dog with lovely head, and an eye, expression and temperament which continually say “I love you.”
In conclusion, my view is that breeders should “make haste slowly” on this question. Optigen has given us a tool, and probably a useful tool, to perhaps get rid of a problem, and not a very widespread problem at that – but use of that tool must be considered in the context of all the other things which need to be considered in order to breed EC’s of good type, soundness and temperament. Let’s not go overboard with this, but approach the whole issue with some common sense! If you have dogs which are going blind, or come from lines which you know have produced blind dogs, by all means use the tool which Optigen has provided if you are satisfied with the science and its value to your breeding program. However, I take the strongest issue with those who would preach that genetic testing for prcd/PRA is somehow a necessary part of good breeding, or that Optigen C dogs should not be bred from, or that only Optigen A dogs should be bred to. Genetic testing for prcd/PRA is, at best, only in its infancy, and can only constitute a very small part of the many factors which should be considered by good breeders.