Bernese Mountain Dog Club of Scotland

 

 

‘Histio’ Update (Malignant Histiocytosis, Histiocytic Sarcoma amongst other official names) by Steve Green BMD Breed Health CoOrdinator       15th March 2018

I have to be as brief and have a lot to pack in so I will get straight to the point. The purpose of this article is to make the case that the breed as a whole should be engaging with the test for this disease, which I shall refer to as ‘Histio’, and should be using it on breeding stock and acting on the results. There are many solid reasons for this which I briefly skip through below and I also comment on some of the reasons given for not doing.

The contention is that ‘Histio’ is the single biggest serious health issue for our breed. Whilst not wishing to downplay the individual impact of any other conditions, across the breed Histio, causes far more deaths and more suffering to dogs (and owners) than hips, elbows and DM put together. This test is currently our only weapon to fight back with. The test is of value for the breed but only if people engage with it and there are potential future improvements that will boost it’s benefit to our breed much further.

No one is claiming this test is yet the finished article, no one is claiming it will eliminate all our ‘Histio’ woes in a single generation, no one is claiming it is anything it isn’t and the creators and providers of the test are all very honest about it’s current limitations and real meaning and are working to improve the test and the way it can be used.

There is an expanded version of this ‘Histio’ article on the breed’s (GB) health web site, www.bernese.co.uk then click on health. More information on everything discussed here can be found there.

For me there is an obvious fact based logic chain when considering the test that goes like this…..

FACT 1 - Cancer is, by a massive distance, the biggest killer of Bernese Mountain Dogs and has been for decades accounting for over two thirds of Bernese in the UK on current figures, 68% of UK BMD die from cancer according to our own Death Survey.

FACT 2– Despite certainly being under diagnosed, and often being determined to be general ‘cancer’ of some sort or ‘cancer of a particular organ’, the most prevalent and serious cancer recorded as affecting our breed, is ‘Histio’ is still recorded as accounting for 23% of UK BMD deaths.

FACT 3 – There is no cure or even treatment for Histio …..

FACT 4 -… therefore the only way we can decrease it’s impact on our breed is to prevent it occurring in the first place.

FACT 5 – ‘Histio’ has a PROVEN hereditary aspect, albeit a complex inheritance and not a simple autosomal, affected, carrier or clear process.

FACT 6 – The bad news about an hereditary aspect is that it will continue to spread through the breed if nothing is done to tackle it. The good news about an hereditary aspect means that with right guidance the incidence of the disease can be reduced with positive breeding practices.

FACT 7 – There is a test that can give an estimation of the likelihood of any individual dog passing on, or developing, ‘Histio’ i.e. assist with the ‘right guidance’

FACT 8 – If every breeder used the test, AND acted appropriately on it, not only would they have a better chance of not producing affected dogs and generally breeding longer living dogs that not will pass on the disease for their own lines and puppy buyers but the overall state of the breed would only improve.

FACT 9 – The nature of ‘Histio’ means that the test cannot give definitive results for individual dog’s or combinations of dogs but it is proven to still give meaningful results. In time the usefulness of these results will become better but as a breed it is what we have at the moment to improve our situation.

FACT 10 – Breeders in the UK do not appear so far to be engaging with the test. It has been around for a few years now and only 39 UK dogs have been tested.

CONCLUSION – Many more BMD breeders in the UK should be using the test.

Summary of some reasons given as to why they don’t
Again, more expansion of these are available in the web site article but I give a few shorter summaries here.
It’s too expensive – How can people even say this for their breeding dogs when considering the price of puppies and stud fees? There are occasional sales with reduced prices but normally the test comes to around £150 all in, well less than hips and elbows, less than 10% of a single puppy price, or typical stud fee etc. Set this against the puppies from several litters or multiple studs and it becomes a tiny price to pay. So, personally I think the cost argument is a very feeble one for genuinely responsible breeders.
It doesn’t mean anything, it’s not definitive, it’s only a guide, it’s not accurate – I could talk at length here because to say this is completely missing the point so I would refer you to the web site article for detail. However, if you want to reduce the chances of Histio in your puppies and increase longevity then why would you not want to do whatever you could to improve matters in this most significant area for our breed? It is not about individual accuracy but about overall improvement. Proper use of the scheme means you will generally improve the health of your line, and the breed over a period of generations.


To draw a parallel in principle, the hip and elbow scoring schemes are also not definitive in, effectively, the same manner but virtually ‘everyone’ does them and all responsible people would say that people should. Responding to hip and elbow scores over several decades the breed has undeniably improved the health outlook for the breed massively. You do not absolutely guarantee good hips and elbows in any specific one of your puppies by using hip and elbow scores as part of your breeding considerations but you increase the odds and over a period of time with each generation the beneficial effect of heeding the tests is cumulative for BOTH individual lines AND the breed as a whole, and the advice becomes more and more reliable.

Every responsible breeder submits to Hip and Elbow scoring but some then say the cancer test is not definitive enough. So, if you are in this camp then the logical question from this is do you only hip and elbow score because you feel you are obliged to for the KC or Assured Breeder Scheme? If you don’t only hip and elbow score because you ‘have to’ why should the ‘Histio’ cancer test be viewed any differently to hip and elbow scoring which ‘almost everyone’ does support? Is the principle not identical?
There’s no point in knowing because you can’t do anything about it / I don’t want to know about my dogs – well in one way you cannot argue with defeatism, it’s a point of view that by definition cannot be broken and it is true that you cannot genetically do anything about dogs that have already been born, (except to test them if they are to be used for breeding). However, clearly this is a wrong premise as the test is about looking forward because as a breeder YOU CAN do something about the future and play your part in beginning to move the breed to a better place by improving the next generation of YOUR OWN DOGS. Surely it cannot be responsible breeding not to try and improve things and reduce the chances of future distress for your puppies and their buyers.
If you’re going to get cancer you are going to get it anyway– in a way this is probably true where no one has tried to take any corrective action but in future litters you can still reduce the odds in your favour for the future of your own stock. Of course, there are other cancers and some of these do not have any known hereditary link and these can be considered plain bad luck as far as we know at this time. However the fact remains that ‘Histio’ is our biggest cancer and YOU CAN do something to reduce the chance that ‘… you are going to get it …” in any dogs bred from YOUR lines.
It’s just depressing to talk about it – this certainly can be true and no one will be in this breed for too long without experiencing some heartbreak and this may often be due to ‘Histio’. However, surely it is even more depressing and creating a self perpetuating situation to simply just be depressed about them rather than embrace a chance to do what can be done to improve matters. Surely the most depressing thing would be to not even have anything to fight back with or even worse not to use something that gives a chance to do something to improve it.
It’s too complicated to do – here I would perhaps have a little bit of empathy as I think the Antagene web site could be a little bit more user friendly but it is possible to work it out and the help is good if you email them. Hopefully, the step by step guide on the web site will be of some help to anyone trying to use the test or if I can help please feel free to contact me. The bottom line is that the test is there for anyone to do if they want to.
Bernese don’t have a cancer problem, people like Steve make too much of it – sorry, but the facts do not bear this out. We may be a bit lacking in hard statistics in this country, a fact the Death Survey is seeking to begin to improve, but the early signs from the Death Survey and anecdotal feelings expressed by breeders and owners for decades all point to a cancer problem. We are not unique amongst Bernese populations all countries have this problem and ‘People like Steve’ do not enjoy pointing this out.
My lines are healthy and long living, I don’t need to concern myself with Histio – it is perfectly true that at times over the years we have identified some kennel lines that exhibit good longevity. So, if you feel you have good long living lines surely you want to keep them? If you introduce a ‘Histio dog’ into your lines you do not get a slight drop in your average life span in your dogs in the way that if all your dogs lived to 10 years previously they will now only live to 9.5 years. It simply doesn’t work like that. You will still get some dogs with good longevity the same as before because they will be unaffected but some of your dogs will now develop ‘Histio’ and will die at younger ages. Some of the families that buy your puppies will lose them at younger ages. Why would anyone want to increase the risk of that when it can be decreased?
I don’t need to take reasonable steps to not breed unhealthy dogs – Apart from the normal ‘ethical responsible breeder’ ethos it is looking quite possible that in the near future the legal requirements for every dog breeder might be increasing and they may have to take more heed of every testable genetic influence. If the Animal Welfare Act reforms, discussd elsewehere, make it legally mandatory for breeders to take account of all health testing for their breed then be sure the lawyers will not to slow to encourage people to take action against breeders who have not done so and produced what the law will describe as ‘avoidable’ or at least ‘reducable’ problems. If you are taken to court you may need to demonstrate that you have ‘done what you can’. I totally accept this is still speculation at press but not without some foundation, I remind you of the headline on Our Dogs newspaper front page in October 2017 when discussing the reforms “Government to prosecute breeding dogs with ‘genetic defects’. Even without any reforms to the Act such prosecutions have already taken place and, as far as I know, always successfully so every breeder needs to be ‘doing what they can’.

IMPORTANT POINTS OF NOTE
– It is absolutely not the intention here to say to breeders that ‘Histio’ testing should always be the single most important factor in breeding considerations and should simply override everything else. Breeders should be free to consider it’s importance to their lines in the same way they do everything else such as Hip and Elbow Scores and EBVs, DM testing, CoEfficient of Inbreeding, temperament, conformation etc. The point here is that it SHOULD be a part of the process.

Neither is it the intention to say only use ‘A grades’ in breeding nor do not use ‘C rated’ dogs, and Antagene themselves and the University of Rennes researchers are the first to make a point of saying this. This is just not practicable or feasible for several big, common sense, reasons and would not be in the best overall interests of the breed. The use and application of the test
guidance IS ABOUT not using ‘C’ with ‘C’ (or with untested), and DEFINITELY NOT ABOUT not using ‘C’ at all. ‘C dogs’ are far too large a proportion of the gene pool to discard completely and will have their share of other attributes to offer the breed.

POTENTIAL FUTURE DEVELOPMENTS
The above all refers to the test and situation as it is today but I must outline some potential important developments for the future of the test, one of which will make it even more useful to have tested dogs. These were announced as part of the update presentations given in France in 2017 although it cannot be stressed enough that two of these are a long way off yet but included here as causes for long term optimism. The other can be progressed as soon as funding can be found. There was news of ……

A blood test for the presence of ‘Histio’ tumours and Beginnings of a Treatment? – it is very early days and the University of Rennes were very keen to stress these were nowhere near to fruition as an available clinical option but the basics have been developed to make them at least theoretically possible. This test could confirm the definite presence of a Histio tumour and much, much earlier compared to what happens currently. ‘Histio’ tumours grown artificially in the lab had been adversely affected by a treatment. There are numerous big and lengthy steps to move this observation to a viable treatment and we are talking years away from this stage but at least it is a tiny bit of hope for the breed in an area where there has been absolutely no hope previously.

Obviously an early diagnosis test is little use without some kind of treatment and treatment is not so good if only administered in the later stages. However, if these two pieces of news are looked at together then the world of Bernese with them both present and fully working would be utopia compared to what we have now so we can only keep our fingers crossed and wish the University of Rennes well.

‘Histio Test’ Web site - There was even more potential good news. Like the others this is still over the horizon but dependent on funding rather than more research and at least giving us some promise of better things to definitely come. This was referred to as HSIMS in a presentation by Dr Anne Thomas from Antagene or, to give it it’s full title Histiocytic Sarcoma Index Mate Selection. I will try to explain this as best as I can using, with permission, a couple of the slides from her presentation.

The ‘Histio’ test checks the markers in nine different sites. Each of these markers can be in three different states so each dog can have almost 20,000 possible options just in the areas of DNA currently looked at for Histio indicative changes. Currently these areas are looked at for each test and basically the number of differences to the typical DNA of the healthy dogs is counted and from the number of variations the index figure of ‘A’, ‘B’ or ‘C’ is calculated. That is to say if a dog has only a few variations from a typical healthy dog it will be graded as an ‘A’ and if it has a lot of variations it will be graded as a ‘C’. In between these extremes will be the neutral ‘B’ dogs whose variations come within the numbers considered as non significant under statistical analysis.

So, a dog could be graded a C due to a lot of changes observed and for example a second potential mate could also be graded as a ‘C’ but, although having many changes they could still be a largely different set of changes present. This could mean, in theory at least, that those two dogs, although both graded ‘C’ might not be completely disastrous to put together as a high proportion of their variations were not being doubled up on. It could also be the, more likely, case that putting a certain two C grades together could be absolutely disastrous and produce a strong predominance of C dogs with a poor prognosis for longer life. At the other end of this principle two ‘A’ graded dogs could have very few changes observed but these could be completely the same variations present so all the changes would be doubling up if those dogs were put together. This could mean that those two particular ‘A’ dogs would not necessarily be as good a combination as some might think. Whilst such scenarios, (‘A-A not so good’ and ‘C-C not so bad’), may occur they will still be very much in the minority and I only use these extreme examples to make the points and the actual practical likelihood of them occurring in this way is very unlikely.
Figure 1

Figure 1 demonstrates this principle showing that two potential matings of a ‘B’ graded dog to an ‘A’ grade, a ‘B’ grade or a second ‘B’ grade. Under the current system you would expect the ‘A’ combination to be the best but you can see that it may be the case that a specific ‘B’ graded dog could be just as good as choosing the ‘A’ grade option producing the same breakdown of ‘A’ ‘B’ and ‘C’ puppies. However, a different ‘B’ dog could be much worse, even disastrous, producing 60% ‘C’ grades. Under the current system there is no way of predicting these outlooks, but if HSIMS were available it would give these much more specific and more accurate predictions in an instant on a web site freely available to all.

Figure 2

Figure 2, shows that, although generally a more desirable combination, in the worst case scenario, even a B to a B has proved to be a bad combination. HSIMS would massively reduce the ‘Histio’ risk factor in any combination of Bernese.

Do not misunderstand this, at the current time as far as anyone can say ‘A’ dogs will produce a better chance of healthy long lived dogs than ‘C’ dogs but if it was possible to assess an individual mating, a more accurate potential result for any exact combination could be estimated. This is one reason why Antagene do not recommend that the breed discards all C graded dogs from the breeding programme but to just use them carefully.

Antagene announced that they want to set a web site up for all Bernese owners and they want it to be free to use. They want to design a web site interface for the database of test results in which you could put your proposed dog and bitch combination and you would get an exact probability prediction of what those two specific dogs would combine together like and what mix of ‘A’ ‘B’ and ‘C’ you could expect, vastly more accurately than the current test. Every single potential mating could have an exact individual ‘Histio’ rating. Although similar in application, this would not be the same as an EBV type prediction system based on antecedents and the effects of the cumulative contributions of relatives, this would be a direct prediction unique to two specific dogs combining together, drawing the data it uses to give the result directly, and only, from the test results of those two dogs.

Antagene asked for €11,300 (euros) from the breed in order to fund development of this web site and I really do feel we should support this plea for funding for this initiative as it is so important to our breed. The French club raised over 800€ just that week-end in response to simply walking around the show and the pre show dinner with a bucket asking for donations. Any donations or ideas for fund raising can be sent to myself.

Conclusion
We undeniably have this horrible disease in our breed but we can do something about it. It will not go away unless we make it and use of the test is the only thing we have to fight with at the moment and into the foreseeable future.

We have been given this tool to begin to improve our breed now and, whilst it may currently be something of a blunt tool, it is still a valuable tool so, as owners and especially as today’s breeders with responsibility for improving the breed for the future, it is up to us to use it. The HSIMS web site process will vastly increase the power of this tool.


The latest figures I have show the UK has almost the lowest percentage of ‘A scoring’ dogs in the testing so far and the highest proportion of ‘C scoring’ dogs, which is perhaps a result of our ambivalence to this issue to date. This means it will not be easy to start with to find dogs to combine with the poorer scores but we HAVE to make a start and begin to try. The test is established and validated to such a degree that to ignore it can no longer be considered responsible breeding. It isn’t perfect and it gives no guarantees for individual dogs but used properly it will improve breeder’s stock and therefore the whole breed.


It appears to be a part of the fabric of our love for the breed in the UK to just accept cancer as a price we, but more importantly, the dogs, have to pay. I’d say that the time has come to move on from this culture of acceptance and begin to proactively do something about improving matters.







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