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May 2016 Report

Following on from our last report which was circulated to all clubs on 28 November 2015, we are pleased to confirm that DNA from 30 JKD cases and 26 controls has been extracted and checked for quality by the Animal Health Trust. This has now been sent to the lab so that the genome-wide association study can commence. This involves the genomes being scanned, attempting to identify the differences between the affected and control groups, hopefully identifying a candidate gene. We anticipate that the results of this research will be available in time for the next Breed Council meeting however, as has been consistently reported, this is not a simple process and success is not guaranteed.

Breed Council previously authorised expenditure of up to £7,200 for this research but we are pleased to report that the final quote received was £90 per sample, making a total of £5,040 which has been sent by cheque to the Animal Health Trust. In addition, Breed Council has covered the reasonable veterinary expenses for individuals who kindly contributed to the controls. This totalled £904.91.

It has taken a lot of effort to get to this point and we would like to take this opportunity to record our thanks to all those individuals who willingly contributed cases or controls. We now hope that the research will produce a positive outcome.

At the same time, we are aware that Bruce Cattanach is pursuing another research opportunity which has been well publicised. We wish him well. As we have said before, until a candidate gene is identified, it is very important that all credible research efforts should be enthusiastically supported by Boxer owners.

Finally, in our November report, we made our position on pedigree publication very clear. By way of reminder we said:

“It has always been made very clear that any cases submitted to Breed Council are treated in the strictest confidence however, in the Summer of 2015, we approached the owners of all cases submitted to us to establish whether they would be prepared to give consent for the pedigree of the case(s) they reported to be made public on the Boxer Breed Council website. Most of the owners gave this consent. However we recently sought advice on this topic through our independent chairman from two independent vets and two independent geneticists. We have been advised that, in the absence of consistent veterinary proof, including relevant post mortem information and histology it would not be good research practice to publish pedigrees. Considering the extremely wide variety of breeding lines involved, we remain concerned that publication of pedigree information in advance of being able to make valid conclusions from the GWAS could actually prove misleading. In terms of breeding advice, the guidance which has been on the breed council website for several years remains the best available and we do not believe that it is helped by pedigree publication.

So in summary, the Health Committee recommendation is that pedigrees originally submitted to it in confidence are not published on the Breed Council website.

However we are aware that the issue of pedigree publication excites strong emotion and so we recommend that a vote on the issue is taken at the next full breed council meeting.”

We would be grateful to receive the Breed Council’s opinion on the important matter.

November 2015 Report

We are very conscious that several months have gone by since our last report, but during this time the Health Committee has been working hard, in support of the proposed AHT research project into JKD, to try and source a sufficient number of controls to go with the 24 cases already held. This has not been easy and trying to persuade owners to provide cheek swabs and to get the necessary blood and urine tests done has required much persistence. However, we are pleased to say that we recently obtained our 24th control and on 11 November 2015 we received confirmation from the Animal Health Trust that all controls had been safely received on 4 November.

In this correspondence Bryan McLoughlin of the AHT wrote: “We'll be including this project in our next strategy planning meeting. As it stands, there are some ongoing projects and papers to finish that will take priority.” In keeping with our earlier discussions, he continues “The initial thought is that we would aim to use 24 affected cases and 24 unaffected controls in a genome-wide association study (GWAS) and this roughly costs £150 per sample, so £7,200 would be a ball park figure, but this could come down if we incorporate the Boxers with additional samples for other projects. When we come to actually placing the chip order then we can provide a more accurate quote. First of all we'll need to quality control all the potential DNA samples, as they have to meet minimum purity and concentration values to be included. When I have better idea of when we'll actually be doing the GWAS then I'll let you know, but my initial thought is that it won't be tackled until the New Year. Presumably the funds to cover the GWAS cost are in already in place so that when we place the order the monies can be provided? Once the samples have been sent then it usually takes about 3-4 weeks before the generated data is sent back, and perhaps a little longer again to analyse. Success is certainly not guaranteed and the best we could hope for from a GWAS is a chromosomal region of significant interest that narrows the genome down to around 1-2%. Further sequencing work would be required to determine the disease causal mutation, and we would certainly keep the breed council informed as to our progress/ findings.”

Subsequent to this correspondence we confirmed that the funding was in place, however, we do need Breed Council formally to authorise the spend up to a maximum £7,200 since the estimate in March was £6,240.

This spend will cover the first 24 cases and 24 controls which was always considered the minimum. As more cases and controls are received it will be sensible to consider incorporating them in the study as well. However, any additional commitment given will be subject to prior Breed Council authorisation.

In a final piece of correspondence received in the last few days, the AHT have confirmed that the quality control on the first eight samples confirms usable concentrations and purity which is encouraging. The latest estimate continues to be that the full quality control on all 48 samples will be done for the New Year. It is not until the project starts that the funding will be paid across.

We will provide updates as the final pieces of preparation come together in advance of the research commencing.

The other issue that the Health Committee has been considering very carefully is the publication of pedigrees. It has always been made very clear that any cases submitted to Breed Council are treated in the strictest confidence however, in the Summer, we approached the owners of all cases submitted to us to establish whether they would be prepared to give consent for the pedigree of the case(s) they reported to be made public on the Boxer Breed Council website. Most of the owners gave this consent. However we recently sought advice on this topic through our independent chairman from two independent vets and two independent geneticists. We have been advised that, in the absence of consistent veterinary proof, including relevant post mortem information and histology it would not be good research practice to publish pedigrees. Considering the extremely wide variety of breeding lines involved, we remain concerned that publication of pedigree information in advance of being able to make valid conclusions from the GWAS could actually prove misleading. In terms of breeding advice, the guidance which has been on the breed council website for several years remains the best available and we do not believe that it is helped by pedigree publication.

So in summary, the Health Committee recommendation is that pedigrees originally submitted to it in confidence are not published on the Breed Council website.

However we are aware that the issue of pedigree publication excites strong emotion and so we recommend that a vote on the issue is taken at the next full breed council meeting.

In closing, while we are recommending that pedigrees are not published (and we also do not believe that the publication of many pedigrees elsewhere has been helpful) the fact remains that if individuals hold an opposite view to ours on the issue of publication then there is an obvious way, frequently advertised online, that they can both access pedigree information and secure publication of any cases.

March 2015

Before I start, please do remember that any issues discussed at Breed Council should remain confidential to delegates and their club committees.

As Breed Council is aware, in order to try and identify more JKD cases we have been working with the Kennel Club and the Animal Health Trust to contact the owners of Boxers on the transfer register for whom the Kennel Club holds a valid email address. We reported on the response to the first bulk mailing in our last update.

In January 2015 we arranged for another bulk email to be sent by the Kennel Club to the owners of all Boxers born between 1 January 2013 and 30 June 2014. This email was sent to 3,589 owners. 1,479 recipients opened the email (44%) and this has resulted in five cases being reported together with swabs. This is 0.3% of the emails which were opened.

This now means that we have 26 cases with swabs at the Animal Health Trust which is in excess of the 24 required to start the research project. We were in touch with both Cathryn Mellersh and Bryan McLoughlin of the Animal Health Trust at Crufts to reconfirm the requirement for controls and we will start to organise these once the pedigrees of the most recent cases are sent on from the AHT. One control is required for every case.

The cost of doing the research (which has been previously agreed and authorised at Breed Council) was originally quoted in 2013 at £120 per swab which would make a total of £6,240 based on the 26 cases held plus corresponding controls. This price is being re-confirmed with the AHT. A reminder of the file note which was presented at Breed Council following our initial meeting with the AHT in November 2013 is attached. This gives full details of the research.

Notwithstanding the fact that we now have the required number of cases to allow the research project to begin, it is still important to gather as many as possible. 24 was simply the minimum number specified. Therefore our continuing message is that the reporting of cases is vital and everyone has a responsibility to encourage this. We would also like to remind everyone of the ‘Frequently Asked Questions’ concerning JKD which appear on the Boxer Breed Council website. These continue to be the best advice available on this complex topic.

Finally, we are aware that some individuals are being extremely vocal in urging the Boxer Breed Council to publish pedigrees of the cases which have been reported. We are also aware that an online petition on this topic was started at the end of 2014 which has since closed, having reached 34% of its target number of signatories.

Previous updates have made our position on this emotive topic very clear and, most importantly, we need to remind everyone that ever since the FAQs were first published in 2012, Question 9 has always been “Will cases remain confidential?” with the answer “Details will only be made available to the Boxer Breed Council Health Committee and its scientific advisers.” We are certainly not going to breach the confidentiality which has been promised to individuals who have submitted cases. However, in the update which will be published after this meeting we will make a request that if any of those individuals wishes for the pedigree of their case to be published then they should simply get in touch with us via the usual email boxerhealth@btinternet.com

We are very much aware that some of the loudest requests for pedigree publication are coming from individuals who claim to have information on many more cases than we do. If they hold a different opinion to us and genuinely believe that there is value in pedigree publication, then we would respectfully suggest that they could proceed to publish details of their own cases.

In closing we would simply like to remind Breed Council that some individuals continue to behave in a highly confrontational manner on this issue, using social media in a very counter-productive manner. It has also been disappointing to see letters from Breed Council and the Health Committee published in full on facebook as part of derogatory online conversations. In future, any replies sent from the Health Committee will include a confidentiality clause as standard.

COPY OF ORIGINAL FILE NOTE
Meeting between the Boxer Breed Council Health Committee and the Animal Health Trust
15 November 2013
Present: Dr Ron James, Tim Hutchings, Laura Clark, Dr Cathryn Mellersh

Following the last Breed Council, the purpose of this meeting was to explore whether Cathryn Mellersh and the Animal Health Trust would be interested in carrying out research, sponsored by Breed Council, to try and identify the gene(s) responsible for JKD.

Key points were as follows:

The research depends on sourcing DNA (via cheek swab) from a sufficient number of affected animals and controls. The genome would then be scanned, attempting to identify the differences between the affected and control groups, hopefully identifying a candidate gene. Of course it was stressed, and is well understood by all parties, that this is not a simple process and success is not guaranteed.

As a minimum, DNA from 24 affected and 24 controls would be required but the more the better
The affected animals should be as well matched phenotypically as possible ie similar age of onset, similar symptoms etc. This is to limit the possibility that we are dealing with different conditions. A protocol needs to be in place to define the characteristics of an ‘approved case’ (see Appendix 1)

As the disease appears predominantly to affect females, then the majority of controls should be female. However, DNA should also be collected from any males that fit the case definition and also from the same number of controls, so there is at least one sex-matched control for each case. A protocol needs to be in place to define the characteristics of an ‘approved control’ (see Appendix 2). As far as the controls are concerned, the important thing is that they are clinically unaffected.

The Health Committee currently has 10 cases, with cheek swabs, which are currently stored at the AHT. These all come from cases which were phenotypically similar.

In terms of identifying more cases it is proposed to engage with the Kennel Club to get an email out to suitable Boxer owners on the transfer register to tap into a much bigger population than the 'show' community. Bearing in mind the juvenile and overwhelmingly female nature of this condition it is suggested, if possible, only to email owners of Boxer bitches under the age of three.

The use of Kennel Club generated email is a technique that the AHT have used with much success. The letter needs to be carefully worded but it would be defining the characteristics of 'affected' and would be inviting the owners of any cases to submit cheek swabs. The letter would be from the AHT, referencing the involvement of Breed Council, and the AHT would handle the issue and collection of swabs directly. Veterinary evidence would need to be submitted with the swabs to confirm the characteristics of the case. This requirement can be stipulated in the letter and we could also continue honouring our current commitment to cover any reasonable vets fees incurred in supplying the swabs together with the supporting veterinary case history.

In terms of the controls, it is anticipated that sufficient breeder support will be forthcoming to source at least 24.

The cost of the research, once the swabs have been collected, is £120 per dog, making £5,800 for the minimum number of 48

Appendix 1:
Protocol for 'approved cases'
• Dogs or bitches who, before two and a half years old, have increased thirst and consequently excessive urination
• The dog/ bitch will usually have been difficult to house train and weight gain is also usually poor
• On blood sampling the blood urea, creatinine and phosphorus levels are above normal levels
• The urine specific gravity is low - usually below 1.02

Appendix 2:
Protocol for 'approved controls'
• Females aged between 5 and 8.
• Normal blood urea, creatinine and phosphorus levels on all controls
• Normal urine specific gravity level
13/09/14 Update

The reporting of new JKD cases remains extremely slow and no new cases have been reported in the last two months. For the cases which are reported, it is still proving very difficult to persuade owners to submit cheek swabs. In March the Health Committee reported that 15 sets of swabs were held at the Animal Health Trust against a requirement to reach 24 before the research project could begin. 18 are now held at the AHT and a further three sets have been sent out, but not yet returned despite numerous requests.

It is now over a month since the bulk email was issued by the KC/AHT to the owners of all Boxers on the transfer register, born between 1 January 2010 and 31 December 2012, and for whom the Kennel Club held a valid email address.

The email was sent to 4,500 owners. 28% of recipients opened the email (1,260) but only five owners requested swabs, none of which have been returned to date and so it is not known if these are genuine cases or not. Even if all five are returned and prove to be confirmed JKD cases this is 0.39% of the 1260 emails which were opened. As long as the KC and the AHT are willing, the Health Committee will try and get a further identical email is sent to all owners of Boxers born during 2013.

Against this background, it remains vital for all cases to be reported to boxerhealth@btinternet.com and every club has an important part to play in this.

In the meantime, the Health Committee continues to believe that publishing any list which names Boxers that have produced JKD would be counter-productive (even if it were legally or logistically possible). However, the guidelines on the website will be amended to include the recommendation that anyone mating a bitch should ask the stud dog owner how many (if any) JKD cases the stud dog is known to have produced. This is putting the onus on the stud dog owner to be open and honest and this is where the responsibility should rest.

The Health Committee recently requested the Breed Council’s support to re-emphasise that no-one should be advertising any Boxers as JKD free. As more cases are reported, it is quite clear that it is impossible to substantiate this claim.

Also, the Health Committee requested more active and public support from Breed Council, especially at times when public criticism surfaces. The Health Committee finds it hard not to be affected by the level of personal abuse that has been directed at them over the past few years and in 2014 it has become intolerable. This abuse often extends to the whole of Breed Council.

On aortic stenosis, we would like to remind everyone about the scheme and the guidelines which apply. It is noticeable that a few breeders are breeding from dogs with high scores when there are available dogs which are scored zero or one in their kennel. Please remember to get a dog or bitch dopplered if it has a score of 2 to try and get a satisfactory Doppler result (ie blood velocity less than 2 metres per second) before using it for breeding. There are a few breeders not following the scheme and it is showing in the results. It is a while since scores of three and four have been seen but they are creeping back in.

24/07/2014 - Update

The Boxer Breed Council Health Committee writes: “At the time of our last report, we told you that we had been provided with cheek swabs from 15 Boxers suffering from Juvenile Kidney Disease. You will recall that we need swabs from at least 24 cases before the research project with the Animal Health Trust can start which will try and identify the gene(s) responsible. By way of update, we now have swabs from 16 cases stored at the AHT and we have swabs out with the owners of a further six cases which have yet to be returned. Some of the additional cases have been identified by our letters in various veterinary journals and some have come through from breeders and owners direct. It remains essential that all cases are reported to boxerhealth@btinternet.com

To help in the identification of further cases (and to give an indication of the extent of the condition in the breed as a whole) we are very pleased to have worked in close co-operation with the Kennel Club and the AHT to get a direct communication out to a very large number of Boxer owners. An email was issued at the end of July to the owners of all Boxers on the transfer register, born between 1 January 2010 and 31 December 2012, and for whom the Kennel Club holds a valid email address. This approach was unanimously endorsed by the Breed Council at its last meeting. The wording of the email appears on the Boxer Breed Council wesite www.boxerbreedcouncil.co.uk under the ‘Latest Updates in the Health section”









































letter

June - Update

If they were unfortunate enough to see it, we are sure that all sensible Boxer breeders and owners will have been appalled at the way in which a small minority have recently been conducting themselves on Facebook. It has been disheartening to see the untruths, misinformation and vicious attacks not just on the subject of JKD but straying into other areas as well. As ever in these situations a degree of self-regulation happens when it becomes abundantly clear to the overwhelming majority that boundaries have been crossed and we note that the public Facebook group which contained the most vitriolic contributions has had most of the material removed. It is a great shame that the administrators did not step in earlier. However, we are depressed to see that the main offenders have simply set up an alternative closed group where they will presumably continue their antics.

Let us make it very clear at this stage that we will most certainly never get embroiled in any of this provocation on Facebook. It is not the right medium for sensible debate as we have seen illustrated very clearly over recent weeks and months. Furthermore, we have submitted to the Kennel Club hard copies of the most offensive Facebook posts which have been made public over the past 10 days which we believe are in obvious contravention of the Kennel Club policy on the use of social media. All clubs were reminded of this policy directly at the last Breed Council meeting.

Let’s now deal with some facts.

The Breed Council voted unanimously to support a proposed research project with the Animal Health Trust on JKD to try and identify the gene(s) responsible. We have seen it insinuated in print that such a co-operation between the Breed Council and the AHT does not exist. This is categorically untrue and we continue to be in close contact with the Trust. However what is true (and which has been made very clear since we announced the co-operation) is that for the actual work under this research project to start, we need to provide cheek swabs from 24 affected cases. At present only 15 have been reported and supplied to the Health Committee. Whenever we see individuals claiming to be aware of cases, we endeavour to be in touch in order to encourage them to submit cheek swabs. The response from people alleging to know of multiple cases on Facebook has, so far, been non-existent but we very much appreciate the honesty and the efforts of the other owners and breeders who have contributed thus far. All 15 samples are held at the AHT pending us being able to identify the remaining cases that are required.

To assist in the identification of additional cases, we have very recently had a letter printed in the Veterinary Record (which goes to all UK vets) encouraging the reporting of cases and this has resulted in one positive response already. We are also working with the Kennel Club and the AHT to get an email out to suitable Boxer owners on the transfer register to tap into a much bigger population than the 'show' community. The use of Kennel Club generated email is a technique that the AHT have used with much success. The letter is being carefully worded to define the characteristics of 'affected' and to invite the owners of any cases to submit cheek swabs.

All we want is for a sufficient number of cases to be reported to us so that the research can get underway. We simply cannot understand why anyone would not be supporting us in this aim especially since this is the only research project we are aware of which is currently on the blocks. If there are others, then we would be delighted to hear about them directly so we can see if there is any way that Breed Council could provide financial support. We take the simple view that the more informed people there are working on different research projects which are attempting to identify the gene responsible for JKD, the better.

So, in summary, we are very focused on getting the right number of cases and samples in order to get the research underway and this is what we have been asked to do by Breed Council. Every right-thinking person in Boxers should be supporting us in this and should be encouraging any cases they hear of to be reported to boxerhealth@btinternet.com

As far as some wider issues are concerned, everyone needs to be aware that the extent of this condition within the breed and its mode of inheritance are not well understood. We have seen it suggested that the condition is widespread throughout the breed and yet we seem to be having trouble getting up to 24 reported cases. We have also seen it suggested that the mode of inheritance is a simple recessive and while some cases appear to support this, others do not. There is also the added complication, when trying to explain the inheritance, that the affected Boxers are almost exclusively female. We are very much aware that everyone wants answers but this is a complex condition and sometimes in life easy answers are not available. Full support of the AHT research project may assist us in coming up with some of the answers.

The average co-efficient of in-breeding of the 15 reported cases is 13%. Seven of them are below 8% and two are 0%. The thought that by avoiding high COI you avoid the problem does not appear to be true, though we do believe that it remains a sensible precaution to avoid breedings which are too close. It is also a fact that a wide range of Boxers have produced the odd case and these Boxers come from an extremely wide variety of bloodlines. JKD is definitely not limited to a small number of bloodlines, as has been suggested, and it is certainly not confined to UK breeding. It is a fact that at a recent championship show 85% of all the entries had a potentially implicated Boxer within the first three generations of their pedigree. With that in mind, and with reports of this condition regularly being made from Boxer populations around the world, we do not believe there are any lines which could be reliably assumed to be JKD-free. However, it certainly does not appear to be the case that dogs produce multiple offspring with the condition. Taken as a % of total offspring, the number of affected cases produced by any one stud dog remains extremely low. This may have something to do with low expression of the condition in the population or it may be that we simply do not understand the mode of inheritance fully enough. It is highly likely that this condition has been around globally, at a low incidence, throughout the history of the breed.

Against this background it would be extremely unwise, even if it were legally or logistically possible, to publish a list of carrier dogs and we note with interest that this has consistently been the advice of an extremely well qualified geneticist who is familiar with the condition. We believe that it would simply prompt an un-educated witch hunt, potentially sending breeders running off to lines which they mistakenly believe to be clear, perpetuating the popular sire syndrome and reducing the genetic diversity of our breed even further. This is arguably what happened at the time of cardiomyopathy and we cannot afford to see that happen again.

In view of the fact that there are significant unknowns, everyone acknowledges that it is extremely difficult to come up with sensible breeding guidelines and, with our current knowledge, it is impossible to have breeding guidelines which guarantee that you will avoid the condition. However, the guideline which has been on the Breed Council website for many months remains the best available. By way of a reminder this states: “Until the facts become clearer the only possible advice is that you should avoid close line-breeding. It is also sensible to wait until your bitch is over three years old to be certain that she does not have the condition herself.”

Unlike the folk who spread their vitriol via Facebook, we choose to believe that the majority of UK Boxer breeders are honest, hard working dog loving people who are trying their best to produce sound healthy puppies they can be proud of. To try and fill in some of the gaps in our knowledge the most important thing at the moment is for everyone to report cases they become aware of to boxerhealth@btinternet.com so that the AHT research project can begin in earnest. It may not come up with the answers that we all want but it is our best chance of making progress.

Looking forward, it is now our intention to issue an information update on a monthly basis, at least until we have the required number of cases reported just so that everyone knows the progress being made. These updates will be made via the Boxer Breed Notes in both Dog World and Our Dogs and also via the health pages of the Breed Council’s website www.boxerbreedcouncil.co.uk/health

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