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Karlin
4th August 2008, 01:53 PM
This was released today:


NOTES ON THE MEETING HELD AT THE ANIMAL HEALTH TRUST, 25th JULY 2008

Present:
Sarah Blott ((Research Group Leader, Quantitative Geneticist, AHT)
Luisa de Risio (Head of Neurology, AHT)
Ruth Dennis (Head of Diagnostic Imaging, AHT)
Cathryn Mellersh (Research Group Leader, Head of Canine Genetics, AHT)
Tom Lewis (Quantitative Geneticist, AHT)
Jeff Sampson (The Kennel Club)
Clare Rusbridge (Neurologist, Stone Lion Veterinary Centre)
Penny Knowler (Researcher)
Mrs V Hull (Chairman, Southern CKCS Club)
Mr R Cornaby (Vice-Chairman, Midland CKCS Club)
Mr D Crossley (Chairman, Humberside CKCS Club)
Mrs L Jupp (Chairman, CKCS Club)


The meeting was sponsored by The Kennel Club and Chaired by Dr J Sampson.


The purpose of the meeting was to discuss data collection for Syringomyelia, genetic evaluation, collection of other health information, eg. MVD.
The following matters were discussed and/or noted:
MRI Scan results:

It was agreed that there is a need to standardise MRI scan results before certification.

To facilitate this, The Kennel Club will organise a meeting of neurologists and radiologist to agree a protocol. It was proposed that a panel should be formed, consisting of a minimum of five neurologists and radiologists, any two of which will be required to agree SM/CM status. It was noted that this system already works well for hip and elbow scoring. An appeal system will be set up to deal with any disputes. Scan results could be assessed by the panellists using a computer link, and therefore they would not have to be based at the same centre. Eventually MRI images will be sent directly to the panel by clinics where the MRI scan has been done.

In the interim, while the panel and protocol are being set up, MRI scan certificates received by dog owners from individual clinics can be sent directly to the AHT. This will need the support of all clubs, to encourage members to send results of MRI scans direct to the AHT, where confidentiality has been assured.

The scheme will not initially be adopted by the KC/BVA but the aim is that the scheme should be developed as a Breed Club scheme and should eventually be adopted by the KC/BVA.

It was suggested that the minimum age for an MRI scan should be 12 months. Dogs scanned under 12 months old will be given an interim report.

KC Heart Testing Scheme:

The BVA/KC are currently considering the introduction of a heart testing scheme for 4 breeds of dogs, including the Cavalier. A meeting will be held on 15th September.

If the scheme is adopted, results will be published in the quarterly Breed Registration Supplement and will appear on the progeny’s registration certificate.

Additionally, the KC is looking at ways by which breeders could access health results of dogs/ bloodlines. This service will be available to breeders and pet owners.

Permanent Identification:

The Kennel Club is currently unwilling to introduce mandatory dog identification.

However, if the clubs set up their own health scheme that includes the need for identification, it is likely that this element would be maintained if the health scheme were later adopted by the KC/BVA.

It was agreed by breed representatives present that clubs would encourage the permanent identification of dogs by microchip or swab, to ensure that data collected for Sarah Blott is valid, and thus help research teams to evaluate hereditary factors correctly. This will assist EBV estimation in a positive and decisive way.

The cost of micro chipping would be approximately £25. Cheek swabs would be £5 and kits are available from the Animal Health Trust.

Club representatives present, considered that these alternative methods could be made available at club shows and events. Dr Samson advised that dispensation could be obtained from the Kennel Club to allow un-entered dogs into such events, to take part in the scheme.

DNA profiling currently costs approximately £65. The Animal Health Trust is currently looking for ways by which this cost can be reduced.

It was noted that microchips should be positioned well down the neck, to avoid affecting MRI scan.

Estimated Breeding Values (EBVs)

It was agreed that all scan results should be sent direct to Sarah Blott for her continuing research. It was noted that a consent form will be needed to allow results to be used for research, and this can be based on current forms used for hips and elbow examination. The format of the form will be agreed by the panel of neurologists and radiologists.

It was noted that first estimates of breeding values are now available for every cavalier in the UK.

There was discussion on when EBVs should be made available to breeders. It was suggested that should EBVs become available too soon, when the programme is still at a very early stage, results could be disappointing and may alienate breeders. It was agreed that more information (ie. further MVD and MRI results) should be obtained before the system is introduced, so that it is more reliable and thus more beneficial.

It was noted that dogs do not have to be scanned to be given a breeding value. There are various ways in which EBVs could be presented to breeders. The AHT will work with the Breed Clubs over the coming months to determine the best way of doing this. The breeding value of each dog will change over the years, as information is obtained on its progeny.

It was noted that Sarah Blott particularly requires information on clear dogs.

This will be a web-based scheme but available in print from AHT, to any breeder on request.

Sarah Blott agreed to produce a special leaflet for distribution to club members, explaining the scheme in layman’s terms.

The AHT data collection will be used to provide breeders with EBVs for safer breeding programmes to reduce the incidence of both MVD and SM, and could include any other condition as appropriate in the future. The EBV system will become even more reliable when permanent identification (PI) is introduced throughout all members’ breeding stock.

CKCSC Hearts database:

The Cavalier Club hearts research database, which is currently being managed by Liverpool University, is to be made available to AHT. This will provide further data information. It should be noted that the strict confidentiality of the database would be maintained by AHT.

KC Information leaflet:

The Kennel Club would be willing to include leaflets with registration documents, informing owners of health issues and screening programmes within the breed, but this needs to be agreed by all breed clubs.

See:

http://www.thecavalierclub.co.uk/health/ebv/intro.html

Also posted today to the website:

On breeding and EVBs and info needed for Blott research: http://www.thecavalierclub.co.uk/health/ebv/genetic_study.html

Karlin
4th August 2008, 02:21 PM
Also see: http://board.cavaliertalk.com/showthread.php?t=26075

Bet
4th August 2008, 07:08 PM
The more this is read the more you realize what a Momentous Step has been taken in the Research of SM and MVD in the Cavalier Breed.

Dr Sarah Blott ,who is doing this Research at the Animal Health Trust here in Britain,will also hopefully through time ,have some answers for other Breeds of Dogs suffering Health Problems

This has been termed State of the Art Research .It is Revolutionary ,and the Cavalier Breed are so fortunate in being chosen to be Pioneering it.

The Cavalier Breed is the first in the World to be being involved in it

I know that at the moment this is not helping SM Cavaliers and other Breeds of Dogs suffering from this Disease or their owners ,but there now is hope for the Future which did'nt seem to be there before .

Bet

Karlin
4th August 2008, 07:30 PM
Yes that's true :). Dr Blott's work is also part of the overall international genome research pioneered by Dr Clare Rusbridge and Penny Knowler, which is a critical element of all of this.

The issue remains, however, whether breeders step up and get scans done as this is what Sarah Blott needs:


It was agreed that more information (ie. further MVD and MRI results) should be obtained before the system is introduced, so that it is more reliable and thus more beneficial.


While EVBs can be given for dogs without them needing to be scanned, if dogs are not scanned in significant numbers, and if heart information isn't submitted, little progress will be made. So hopefully the clubs and breeders will strongly support these schemes and get the MRI scans and cardiologist information. This of course will be especially important for frequently used sires! As the notes make clear, Sarah Blott feels there isn't enough information yet for the EVBs that do exist to be released for breeder use.

Margaret C
5th August 2008, 09:42 PM
As the notes make clear, Sarah Blott feels there isn't enough information yet for the EVBs that do exist to be released for breeder use.


There is probably a great many scan results that have not yet been added to Sarah Blott's research data.
Owners should not take it for granted that all records have been shared or passed on to the genetics researchers.

UK cavalier owners that have had their dog MRI scanned because they were showing SM symptoms, or because they wanted to check their breeding stock through one of the low cost centres, could really help this groundbreaking initiative by sending their scans, certificates or reports to:-

Dr Sarah Blott
Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, CB8 7UU
sarah.blott@aht.org.uk

Margaret C

Karlin
5th August 2008, 09:50 PM
Which reminds me that I need to send my results now that she is gathering them! :) Or at least make sure they have been passed on.

Bet
6th August 2008, 11:28 AM
Could I further mention about this Research.

I just don't know whether it will ever be known as to the cause of SM

Is it an AUTOIMMUNE Condition ,UNKNOWN

Are some Dogs Genetically Susceptible to Adverse Reactions from their Vaccinations ,also UNKNOWN

How can it be being linked to the Shape or Size of Heads ,since other Small Breeds of Dogs with SM have different Head Shape Heads and Sizes

So what the Cavalier Breed is left with is the new exciting STATE of the ART ,Revolutionary Research which Dr S Blott is carrying out at the Animal Health Trust on SM and MVD Diseases in the Cavalier Breed

Since SM has appeared out of the blue as the saying goes ,does it matter where it's come from ,the answer I think ,is to Breed it out of the Breed,

Hopefully this Research will be able to do that .

Bet

Karlin
6th August 2008, 12:14 PM
Bet, her research is also closely connected to what Clare and Penny are doing, as Sarah has explained herself. :) She needs more of the same information the other researchers are basing their work on and asked for breeder cooperation when she spoke at Rugby. Sarah also believes the condition to be a primarily hereditary condition and what she is doing is directly linked to the genome work. The EVBs will not have much meaning without the molecular genome study in Canada pioneered by Clare and Penny, as Sarah explains below. Also she feels the EVBs will be based entirely on hereditary elements -- I am not sure from what you are saying above if you realise the EVBs are totally based on inheritance? Because if there is as much doubt as you perhaps feel, and if environmental elements are the primary cause and not a more minor issue, the EVBs will have absolutely no affect at all!!

If you truly believe the EVBs will help, and that this is important, helpful work for breeders, this has to be based on a belief that SM is primarily a hereditary condition. The size and shape of heads may possibly have something to do with it as that is hereditary as well, but so far there's been no correlation. But remember, research has only begun in this area and there's much distance to cover yet.

I certainly hope you are incorrect in wondering if SM is mostly an autoimmune condition -- as if it is, Sarah's work will be utterly pointless and meaningless!! :eek: That would be devastating for the breed.


Syringomyelia is believed to be a complex disease, where the disease phenotype results from the effects of several genes plus environmental influences. The phenotype includes not only the affectation status of the individual but also clinical observations and measurements made from MRI scans. In order to determine the genetic basis of the disease two different approaches are being taken. The first uses a population-based approach, where phenotypic measurements and pedigree information are used to estimate the heritability of the disease. This requires that we have accurate phenotypic measurements, including MRI scans, on as much of the population as possible, together with pedigrees so that genetic relationships between individuals can be identified. Where information exists on other diseases, such as Mitral Valve Disease, this can also be included in the analysis allowing genetic correlations between diseases to be established. It is important to know about correlations, or relationships, between diseases so that any selection strategies take account of the possible influence that selection against one disease may have on other diseases. The second approach to understanding the genetic basis of a disease is to use molecular genetics and gene mapping techniques to try to identify the underlying causative mutations. This approach is also being used to try to identify genes causing both Syringomyelia (SM) and Chiari Malformation (CM) in the Cavalier King Charles Spaniel (CKCS) and other toy breeds such as the Brussels Griffon. It is hoped that this will identify regions of the genome harbouring the genes causing these conditions.

Data collected by Penny Knowler and Clare Rusbridge is currently being used as the basis for the population-based analysis of heritability. Their database contains clinical observations for SM and CM on around 1,400 dogs and MRI scan results for around 700 of these dogs. We have also been given access to the full UK Kennel Club pedigree records for CKCS. This enables us to estimate the heritability of SM and the genetic correlations between SM and measurements made from the MRI scans. The information obtained from this analysis then allows us to derive estimated breeding values (EBVs) for all measured dogs as well as all dogs in the pedigree. Once the results of the gene mapping studies become available it is hoped to bring this information together with the population analysis to facilitate the calculation of genomic breeding values (geBVs).

She continues:


Early estimates of the heritability of SM suggest it is around 0.7-0.8* or that 70-80% of the variation between individuals is genetic in origin and about 20-30% is environmental. In the case of SM not much is known about the environmental influences and these may include in-utero or developmental effects. The heritability is sufficiently high, however, that genetic selection against the disease should be very successful. Heritabilities for Chiari Malformation, Cerebellar Herniation and Medullary Kinking are also very high. Genetic correlations between these traits and SM are positive and, interestingly, less than one. This suggests that different genes may be controlling SM and CM and that it will be possible to select against SM even if dogs have the malformation (CM).

She especially needs MRIs from dogs people believe are unaffected and possibly clear.

Maybe it is time to start a campaign to get the clubs organised around fundraising towards scanning programmes -- something many people have been advocating for years now? Maybe you would start to push for this given how crucial you see Sarah's work, which is based on the need for further MRIs to help both her work and -- as a closely connected element of Sarah's work -- the genome work in Canada? I would happily fundraise for Irish breeders!! I'd also happily help out with a campaign, setting up a website, or whatever for fundraising in the UK or US or Canada... anywhere that this could be of help. I do not think a broad enough array of MRIs from hopefully unaffected dogs will ever come in unless the clubs really take this on as a serious project needing club funding at national level, internationally.

Alison_Leighfield
6th August 2008, 12:53 PM
Are MRI's and the written reports only wanted forn Cavaliers that have pedigrees? what about others like rescue/PF that have been scanned with no history? also will they be returned in time?

Alison.

Karlin
6th August 2008, 01:21 PM
You should email Sarah Blott as I don't know any more detail than what she explains at the link I posted above from the Club site. But I think really she needs only dogs with pedigrees as they cannot get EVBs from dogs without them as they are based on inheritance and the network of relatives. I also think they simply need copies -- not the original documents.

Bet
6th August 2008, 03:12 PM
May I answer Karlin by saying that I'm not suggesting that SM is an AUTOIMMUNE DISEASE .

The Bottom Line is nobody knows .

Also about Pedigrees ,what I think has happened is that some Cavalier Pedigrees are found to be flawed ,that is why they have now to have I believe to be Cheek Swabbed, Micro-chipped ,orTattooed

I know that in America ,the CKCS CLUB USA ,now require Cheek Swabs before Cavaliers are Registered ,because some of the Cavalier Pedigrees were found to be flawed

Bet

Bet
6th August 2008, 03:32 PM
To add to my previous Post ,Now that the UK CKCS CLUB and the KENNEL CLUB are supporting Dr S Blott in her Research ,and as I mentioned I believe the only way is for the SM Disease to be being Bred out of the Breed ,which I believe this type of Research does

Hopefully ,as was mentioned on the UK CLUB WEB SITE ,Dr S Blott will be giving more information to CLUB Members shortly

Bet

Bet
6th August 2008, 03:53 PM
Sorry about this Folks,

Iforgot to mention that on the INTERNET there is mention from the KENNEL CLUB that DR S Blott has been given £100,000 recently

So I guess the money is there ,whether it's all for SM Research I dont know ,

Also Dr Mellerish who was at the Meeting and is also a Geneticist at the AHT has been given £200,500 from the Kennel Club's Charitable Trust

Bet

Karlin
6th August 2008, 05:35 PM
I think the bottom line is that no one specifically knows what causes MVD either, but you have long been convinced that testing hearts and adhering to the MVD protocol is the best approach! :)

But in addition, Bet, there are very clear signs that indicate the hereditary element is extremely important or else Sarah would not even bother with the EVBs. If there is a stronger environmental cause -- then her EVBs will be meaningless as will her two year study.

The bottom line is -- she needs MRIs to be done, she needs them done on dogs that people do not think have SM, she needs full breeder buy in and support, she needs breeder support of the Canadian genome study as she feels the EVBs based only on pedigrees and existing MRI results are not going to be that adequate and need the genomic element to be truly useful.

Many, including more recently, yourself, have argued there's little point in breeders doing any MRIs. Have you changed that view? Because without MRIs, Sarah's work cannot succeed as she herself notes. As she and the breeders who attended the meeting recently agreed, the information she currently has is not broad enough to release in the form of initial EVBs. Who will fund and supply further MRI information? icon_nwunsure This is going to be a huge issue for this research to succeed or even for it to move forward.

It is worth mentioning this again -- there is simply no point in Sarah Blott doing her EVB study if people do not believe there's a stronger hereditary than environmental cause. If you are unsure, than Sarah's work cannot be revolutionary and a breakthrough, because it means it is just as likely to be totally useless. The only way a clear understanding of the role of inheritance will emerge, is if there is club and breeder support for the genomic work in Canada as that is the key to unlocking the role of inheritance. That is why Sarah so very clearly asked for support for that work when she spoke at Rugby, and why she takes the time to explain the role of that research in her own work in the document on the Club site.

Or to put it another way: if someone believes that the hereditary aspect has not by now been well demonstrated on gathered evidence, and if someone feels there's little point in doing MRIs, then there's also no basis in believing in or supporting Sarah Blott's study because it is ENTIRELY based on the strong evidence for the genetic component to the condition, and relies totally on getting in more MRIs.

I was hoping to see breeders -- especially those involved in this meeting -- discuss their views on this on the CKCS-SM discussion list but it is surprisingly quiet after you posted about the meeting notes! That makes me worry there is little support for Sarah Blott's work because there is so far so little public demonstration of support or discussion either way on what breeders are thinking. :( I am looking forward to some eventual public discussion of such an important meeting. There are so many more breeders interested in the topic and waiting for direction from the clubs internationally that are on that list or other lists, so I hope some public discussion will take off.

Bet
6th August 2008, 07:13 PM
Karlin ,

I cant answer your questions ,I guess I'll be like many other lay People where this State of the Art Research is concerned,being conducted by Dr S Blott

Maybe you should be asking Dr Blott herself or wait until her comments are to be being given to the lay people about her Research Work ,probably this is why there has been no discussion on this subject .

That nobody understands it ,it's way ,way above our Heads ,we will just have to have patience till it has been explained to us to have a better understanding of it .

This is Revolutionary Type of Research ,we are not experts ,but we should be grateful that the Cavalier Breed is involved with it and that the Kennel Club has given so much money for it to be being carried out

I for one am just waiting till I can understand more about it ,and because the UK CKCS CLUB have such hopes of this Research ,I'm pinning my hopes on it.

Bet

Karlin
6th August 2008, 07:44 PM
Actually, Bet, it isn't too hard to understand what she is talking about if you read through her description on the Club site -- Sarah herself says her EVBs are based on MRIs and pedigree work that she feels clearly demonstrate the strong role of inheritance. She also talks about this at Rugby, on the CDs I made of the event. But it is a bit technical, that's for sure!

I am not wondering why pet owners aren't discussing this proposal, because the meeting was really about what steps breeders and the Club will take next. I am just wondering why the breeders haven't discussed this very important meeting after you posted the notes! I don't breed, so I cannot provide any further information Sarah needs for research -- she has the scans and pedigrees from my two that have been done, as far as I know, and will receive them if she hasn't. But my other dog Lily is of no value as I don't have a pedigree for her; she's a pound rescue. But as a pet owner very supportive, like you, of her research, I would certainly like to understand better what club members think of the meeting and the notes, and if there are any ideas as to how to concretely support Sarah's work by getting more MRIs to her. :)

But I am still curious how you can support Sarah Blott's work and feel it is so important if you disagree with or at least doubt all its premises? This makes no sense, if you doubt the validity of the work Clare and Penny and others have done on showing the role of inheritance and doubt the value of the genome scan, and feel unpersuaded about the role of genes and heredity in SM. Logically, there would be far greater reason for you to dispute the value of Sarah Blott's work, than say Clare Rusbridge's. If you doubt the role of inheritance, you would be right to continue arguing that the role of inheritance should be more firmly understood BEFORE Sarah Blott gets involved and tries to develop EVBs that are completely based on existing research on inheritance.

In other words, Sarah Blott's work is absolutely pointless unless the existing work by Clare, Penny and others on inheritance is accepted as the cornerstone of the EVBs. Because that is what Sarah Blott is basing her work on!

Bet
6th August 2008, 09:25 PM
I have just read Karlin's Post where she mentions that the Hereditary Aspect of SM has now been well demonstrated on gathered evidence

What I've been trying to explain is that ,and this is nobody's fault ,is that there are some Cavalier Pedigrees flawed

As was said at the Meeting ,this is why there should be Permanent Indentification of Dogs by Microchip or Cheek Swab ,

This is to ensure that Data collected for Dr S Blott's Research is valid ,and thus help the Research to evaluate Hereditary Factors correctly

This will assist EBV Estimation in a positive and decisive way

I have been involved in collecting Cavalier pedigrees for over 20 years and know that there are some flawed

Because this new Research is what is called State of the Art Research their must be no doubt about the Authenticity of the Pedigrees ,if there is any doubt at all then Dr Blott's Research is in trouble.

I dont know anything about the Pedigrees for the Genomic Work in Canada ,but I would expect they will have been checked in the same way as well to make sure that none were flawed

Bet