Research Update

NEWS UPDATE ON EPILEPSY RESEARCH FROM THE AHT – July 2013

It was disappointing that the first genome wide scan did not give the hoped for leads for the mode of inheritance of primary epilepsy in the keeshond. however, not to be disheartened the research team continue to collect samples from keeshond’s affected by primary epilepsy in order to run a second larger genome scan. The progress of this is dependent on owners notifying the team and srubmitting a DNA sample of their dog along with the clinical veterinary information supporting diagnosis. Read the full AHT report.

 

NEWS UPDATE ON EPILEPSY RESEARCH FROM THE AHT – October 2012

After many months of communication and support from breeders and owners world wide, we have reached the stage where the collected samples have been qualitiy controlled and prepared for the Genome Wide Association Scan. This is a very exiting time for our breed and hopefully will provide the necessary data to progress with the fine analysis.  Read the AHT report

 

NEWS UPDATE ON EPILEPSY RESEARCH – 13 October 2011

For those of you with epileptic dogs life can be very stressful, particularly if your dog suffers from clusters of fits that are unpredictable
and tend to merge together into long periods of abnormal behaviour. For vets too, this is a difficult condition to manage and therefore the genetic unravelling of epilepsy cannot come quickly enough for vets and owners alike.

After the disappointment of the collaboration with Cornell we entered into a new agreement to work with Cathryn Mellersh and Sally Ricketts at the Animal Health Trust (AHT) and they have been collecting our samples for us co-ordinated by Bryan McLaughlin. Recently, thanks to the Herculean efforts of keeshond breeders and owners and some unrelenting pressure from the breed Health
Secretaries of the Keeshond Club and her colleague in the North of England Keeshond Club, Jane Saunders and Anji Marfleet, the longed for target was reached. We now have 31 samples from dogs with epilepsy and many more control dogs.

What happens next? Now the interesting bit can begin. The AHT are going to perform genome wide association analysis (GWAS) on our samples to see if they can narrow down the bit of DNA we are interested in. As many of you will know, the genome is the full complement of DNA that we have in our cells that is organised into separate units called genes. Genes, and therefore DNA, are made up of combinations of four separate nucleotides. Our dogs with epilepsy will be compared to normal dogs to see whether they differ from them in certain areas of their genome. To look for these differences the AHT will make use of things called SNPs or single nucleotide polymorphisms. These are the result of natural variation across the genome and represent DNA differences between individuals within separate families or lines. SNPs are used to define the haplotype of an animal where the term haplotype refers to the
inheritance of a cluster of SNPs.

By examining haplotypes, we can identify patterns of genetic variation that are associated with healthy dogs and those with epilepsy. For instance, if a haplotype is associated with epilepsy, then we can examine stretches of DNA near the SNP cluster to try to identify the gene or genes responsible for causing the disease.

As you can imagine, this process is not quick and the analysis of the data that it yields is complex. I guess what I’m trying to say is ‘don’t hold your breath!’ But, and this is a big but, at least we are on the way to trying to unravel the disease in the way that I referred to in my first paragraph and that means that we have made progress.

One of the last things I have to say is a massive thank you to all of the people who have contributed their time, energy and enthusiasm to this project. I really hope that we will have some results to share with you soon as I know that many people have been waiting a long time for this to come to fruition. Our samples have been collected from all around the world so this has truly been an international effort.

If, by some miracle, there are still some people out there who have an epileptic keeshond, please do not delay in sending a sample. The AHT are used to working with DNA samples extracted from buccal swabs (cells scraped from the inside of the cheek) so to contribute to this project you do not even have to take your dog to the vet. If you are confident that your dog has a diagnosis of Idiopathic Epilepsy then we would like to hear from you. If you are not sure then I am happy to discuss your dog’s condition with you. You will be sent a sampling kit from the AHT with instructions how to use it and a short questionnaire about your dog. It is a simple, quick and painless procedure to
collect the samples and you could be doing your bit to help future generations of keeshonds. Please act now – we need your epileptic dog!

Barbara Skelly MA VetMB PhD CertSAM DipACVIM DipECVIM-CA
Department of Veterinary Medicine
University of Cambridge
Madingley Road
Cambridge CB3 0ES
bjs1000@cam.ac.uk 
 

Swab packs can be  obtained from Bryan McLaughlin at the AHT. bryan.mclaughlin@aht.org.uk

NEWS UPDATE – 28 August 2011

The old saying  ‘everything comes to those that wait’ proved true last week when a shipment of samples from kees diagnosed with primary epilepsy arrived at the AHT from The University of Cornell, School of Veterinary medicine. Thanks to Dr Richard Goldstein for agreeing to forward them to our research, with the permission of the owners.  Along with others that have been arriving at the AHT from around the world the total now stands at 29 with two more coming from the USA and Europe.

The team are now ready to start preliminary analysis of the samples. This is an exciting time for our breed. Let us hope and pray that the team will be able to identify the genes responsible for inherited epilepsy in our breed and go onto develop a test to prevent future generations being afflicted with this condition. We have done it once with PHPT, so hope we will soon have a second DNA test.

NEWS UPDATE – 17 June 2011

Three months from the previous update and progress has been slow. The good news it that the target of 24 samples from dogs over the age of eight years, who do not have epilepsy has been reached. We now have the ‘controls’

What is still needed are the samples from dogs diagnosed with primery epilepsy. Information on the diagnostic stages for this can be found here.

Thanks to the support of breeders and owners around the world more samples are being collected from dogs who have epilespy. Nobody wishes any dog to have this condtion, but if you are in the unfortunate position of owning ab Epileptic dog, please support this vital research to help future generations. This research project is achievable but samples are the essential ingredient. All the information about how to participate can be found in the article below.

 

DNA research into epilepsy – a new beginning  – 21 March 2011

Last Friday I heard the exciting news that following various setbacks, Dr Barbara Skelly of the University of Cambridge UK  has formed a new research partnership with Dr Cathryn Mellersh, a geneticist at the Animal Health Trust in Newmarket UK.

The AHT is in the forefront of genetic research into inherited conditions in the pure bred dog and Cathryn is keen to collaborate with Barbara for the good of our breed. Technology has improved immeasurably over the past few years and they do not need very much DNA from each dog for the Illumina-based screening process.

It is regrettable that the work with Cornell has not been fruitful but with advancing technology we are now able to use cheek swabs which will make collection and shipping simple. The AHT are happy to use their DNA collection resource for this project which means that sample collection will be through cheek swabbing (4 per dog) by the dog owner.

How many samples do we need?

We need 24 epileptics and 24 controls to run their Illumina-based screening process. Epileptic identification is very important i.e. has the dog been diagnosed through a logical sequence of diagnostic tests. Epilepsy is a diagnosis of exclusion so all other causes of seizures must be ruled out before the dog is found to be epileptic

How does the Illumina – based screening process differ?

The screening will look at the DNA of the affected samples against a similar number of ‘control’ samples. The control samples will be from dogs over the age of 8 who have not shown any clinical signs of epilepsy. We can gather these in the UK.

This method of mapping does not rely on collecting and amassing family samples and data. When an epileptic is identified it is not necessary to sample siblings or parents, nor does this particularly help. The method relies on excluding all differences except the one (or several) differences that make that dog epileptic. It is not vital to have a full pedigree as long as the keeshond is pure bred.

How can the owner participate?

As it is by cheek swab, we hope our request will be better received as it puts the collection and shipping within the owners own home environment, and carries no cost beyond the cost of postage.

Collection packs can be requested from the AHT from their sample collection co-ordinator, Bryan McLaughlin (bryan.mclaughlin@aht.org.uk). These can be requested on a case-by-case basis or in bulk for a show.

Can we be successful?

I hope so. The success of this relies on individuals and breed clubs around the world working together and combining resources so that we can gather every possible sample from keeshonds diagnosed with primary epilepsy.

Barbara estimates that we currently have 11 -12 samples so we are half way towards our goal. We do not have access to the DNA sent to Cornell, so if anyone has previously participated by sending blood there, we would ask them to resend to the AHT via a cheek swab pack.

And finally  

Barbara is keen to get back to work for the good of our breed. It is true that a gene screen has failed once but time has moved on and these information methods are improving all the time. We have the UK Kennel Club research grant to do this again but we need to work to a tight time schedule.

We are a small breed individually, but as a world wide family of keeshond lovers we can achieve this goal. We own the best breed of all so we owe it to them to do the very best we can on their behalf.

Please support Barbara Skelly and Cathryn Mellersh to achieve our dream of a genetic test for inherited epilepsy in the keeshond.

Owners contributions can be entirely anonymous if they wish, however if anyone wishes to contact Barbara her details are

 Barbara J Skelly MA VetMB PhD CertSAM DACVIM DECVIM MRCVS

 

    Department of Veterinary Medicine
    University of Cambridge
    Madingley Road
    Cambridge CB3 0ES

    e-mal BJS1000@cam.ac.uk

NEWS UPDATE – 19 March 2011

Following a disappointing setback in the quest to identify the genetic cause of Epilepsy in the keeshond, Dr Barbara Skelly has advised that we will be taking a new path in collaboration with the Animal Health Trust in Newmarket. Advances in DNA research, mean that sample form dogs diagnosed with primary epilepsy can be gathered via cheek swabs (4 per dog) and sent in confidence to the AHT.