Linda Holland has asked a number of questions about SAS and she has asked me to answer on this list.
The questions are difficult to answer in part because there are no certain answers but more because they are not set against the real situation.
A problem is that the mode of inheritance of aortic stenosis has not been clearly established even in the researched breed, the Newfoundland. In this breed some evidence was obtained that a single dominant gene was responsible but this became confused upon crossing to another breed.
From my background in genetics I would expect that a single gene is primarily responsible for the condition but this is not to say that any other genes such as those playing a role in heart development, blood vessel walls, elasticity of the latter, the biochemical milieu behind the nodule and fibrous ring formation that leads to AS etc do not play a part. I drop the first S of SAS for reasons that will become clear later.
Add to this that the cardiologists choose to GRADE the murmurs and MEASURE blood velocities and you have a situation in which a polygenic inheritance is almost forced. Blood velocities vary even in dogs with normal hearts - no AS in their breed, and I don't think any cardiologist would put hand on heart to say that such normal dogs never have at least minor murmurs.
So a real question is what is normal and how in the variability does one distinguish AS? Well, I don't think the answer is clear but, nevertheless, if one knows that some dogs in the breed are dying or are badly impaired, some action needs to be taken.
The UK control scheme takes the simplest approach; we simply say that we will breed from the best and avoid the worst. This is familiar territory to dog breeders; everyone can take part. All that is needed is an economical test such that everyone can test all their dogs and that the essential results, meaning those which are the best, are available for all to see. This enables those with bitches to choose a dog of the required standard and stud dog owners have the possibility of being careful which bitches they accept.
This is all fine if the opportunities for testing are widely available and the test is reliable. Many readers will have read posts in which I have talked about the difficulties on both points. In the UK we have had really bad problems over the near-10 year period of testing. But, having been seriously depressed by these problems I now find that cardiologist after cardiologist is now reporting that the numbers of referred cases of Boxers across the whole country has dropped dramatically. At Edinburgh, the starting figure position was that Boxers alone made up 45% of all referred cases of AS. That was in 1990. Now Boxers are not even among the top ten breeds. Despite all these problems, and all the problems with distinguishing the minor grades upon which the scheme was built, the scheme has been remarkably successful.
So, now, how to answer the questions:
1. If sire and dam are clear, is it one parent or both that would be carriers?
Sire and dam clear, is one or both responsible for a case? Depending upon the frequency of any single responsible gene, it might be one, or the other; and we don't know what happens with any hypothetical homozygote with 2 doses of the gene. [if one takes brindle as an example, when you get a brindle, does this mean that one or both parents are brindles? Could be either or both.Same rationale!]
2. If one or both are carriers what does that mean in regard to their parents and so forth?
Same line of argument can be applied to the question re grandparents and behind them.
3. Does SAS skip generations? In other words, could it be that the affected dog got it from a great-grandfather? Does AS skip generations?
Obviously normal appearing dogs can produce affected, so there is at this level a skipping of generations. But are the parents really normal? Here we get to the grading. This is supposed to distinguish dogs with the most minor levels of AS but the system is not that perfect. [Taking the brindle example again, most brindles are distinct from reds but under poor light conditions there would be a possibility of missing the most lightly marked tiger brindles!!]
4. Is there a test available to determine which one is a carrier?
Testing for who is a carrier? I think it is obvious that the testing systems are not infallible at the murmur or blood velocity levels etc and there is no DNA or other such test.
5. Should parents of affected dogs be removed from breeding?
Depends how affected the pup/s are, and how many. It may be possible that any extensively used dog may produce one or more seriously affected pups, but if the mean score of his progeny (to bitches of known scores) is low, then he is one of the best. However, the other side of the coin is where a dog regularly produces more seriously affected pups, or even higher scoring pups, then he would be one to avoid. Here a little bit of history might be justified; we had a dog that graded as 0 on two occasions up to 18 months of age. At stud he was found to produce a number of Grade 2 progeny, to Grade 0 bitches. On further retest it was found that he now had a Grade 3 murmur and an elevated blood velocity on Doppler. He was clearly not a dog to breed from, but what had gone wrong? On ultrasound scanning it was found that the stenosis (narrowing) involved the valve itself and therefore was not, as commonly recorded, below the valve (Sub-AS). Valvular AS appears to progress and get worse wheras sub AS appears to change little after adulthood. So it can be seen that there are 2 messages in this highly informative case. At least one other such case has since been found. Add to this that the "bad" days of AS in UK Boxers are said (I have no evidence) to be largely attribuatble to some extensively used stud dogs which had louder murmurs. There certainly was a family of seriously affected cases.
6. What does this mean in regard to the affected dog's littermates? Should they all be removed from breeding whether or not they have it because they could be carriers?
Difficult. I think at this stage one should rely more on the test results, preferably more extensive and more rigorous in view of family background. This would certainly be the best prospect if the condition is at all frequent such that clear lines cannot be recognised. I am sure that this is the case.
By the way there does seem to be some link between AS and BCM; they have often been found together. This may only mean that a heart impaired by one condition may be more susceptible to another. Who knows!
7. Should any dog with SAS be bred? I have heard of 3 categories, Mild, Moderate, & Severe. Also one that I am not really sure exists "Borderline".
As must be evident it is best to avoid the more seriously affected. Where the line is drawn will vary with the magnitude of the problem within the breed/country. If there are few affected with even minor murmurs, then one can be hard; if there are many, one must be less rigorous. In the UK we tried to knock off the worst 10 -15% with Grade 2 as the starting cut off point, but with tougher grading we find we have 30% Grade 2s and it is hard to take such a high proportion of dogs out of the breeding population. However, this number can be cut by about 50% by retesting (and Doppler at a 2.00 metres/second blood velocity limit which everyone admits is too high).
8. Should cardiologists treat affected dogs? Are there medications?
So far as I am aware there is no treatment other than perhaps sedation for AS. For my part I would prefer to let dogs have some quality of life and risk sudden death or fainting, but!!! In any case it is only the Grade 4s and above which are at risk. Very few Grade 3s and no Grade 2s develop clinical symptoms. For BCM there are surely some treatments possible but I know little about this disease. Obviously one should not treat to allow breeding, only to to alleviate pain etc.
9. Does SAS worsen as the dog gets older?
Supposedly not, but I have cited one case. It is supposed to develop with age from puppyhood through to adulthood. Having said this I have no evidence from all my records to support this. Aside from the latter this is really a veterinary question and should not be addressed to me.
10. Do dogs with BCM typically have problems with SAS?
I have commented on the tendency for dogs to have more than one heart condition. I am afraid that this response is no more than an off the cuff answer to Linda's questions. As this is a complex problem. I cannot have done it much justice but this is my immediate response to what I regard as a very delicate and perplexing situation.
Hope this helps.
Bruce M Cattanach
MRC Mammalian Genetics Unit
Harwell, Didcot, Oxon OX11 0RD, UK