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At times it seems unbelievable but it’s now 6 years since I took over the role as CA coordinator for the ISCGB. Most of the time it’s been an uphill struggle but in the last two years we have started to make some real progress regarding the collection of samples needed for DNA sequencing and hopefully, some time in the future, a DNA test for CA.

A lot has happened since I wrote the last update in November 2003 and it’s taken up most of my spare time, and almost all of my energy, but I hope that you will agree with me when I say that it’s all been worthwhile as we are beginning to see light at the end of a very long, dark tunnel.

When I wrote to the Animal Health Trust last October about the possibility of adopting the “candidate gene” approach, to try to identify the gene which carries CA, I sent a copy to Dr. Jeff Sampson, KC Canine Genetics Coordinator, just to keep him up to date with our progress. I received a very interesting reply from him suggesting that I contact Dr. David Sargan, a molecular geneticist at Cambridge University Vet. School, who was beginning to investigate an alternative approach to identifying genes carrying hereditary diseases, (using linkage analysis), known as homozygosity mapping that might be successful with fewer samples. (Dr. Matthew Binns and his team at the AHT have successfully used the traditional linkage approach in order to identify genes responsible for inherited diseases which require DNA samples from families in which one or more affected dogs have been identified. Samples from the affected dogs, their unaffected siblings, and parents etc. are needed and the more samples that can be collected the more likely it is that any research project would be successful.)

I contacted Dr. Sargan, Senior Lecturer in molecular pathology, in November last year and we have corresponded on several occasions since. He is very interested in CA and is keen to assist us in any way that he can. He and Dr. Matthew Binns spoke at the end of November and, at that time, both thought that there had been too few cases to make much progress using genetic linkage approaches, leaving the only way forward a “candidate gene” approach; where they hypothesise that the disease is equivalent to a better characterised condition (probably in humans or laboratory mice) and look for mutations in the dog equivalent of the gene mutated in these conditions. However, since November the number of samples held by AHT has increased considerably so, for the time being, we shall assume that both methods of research may still be options available to us.

Apparently there are many distinct inherited cerebellar degenerations in humans; one of the most complete keys to human inherited conditions list 273 separate entries under “cerebellar ataxia”. Dr. Sargan said that they cannot hope to look at all these genes so must narrow the field to just a handful or two at the most and this requires the assistance of a veterinary neurologist. By pure coincidence at the very same time that I was looking to find a neurologist to take over from Dr. Mike Targett, as he had left the Royal Veterinary College, and my telephones calls to the RVC had drawn a blank, Dr. Sargan suggested that his colleague, Dr. Nick Jefferey, Lecturer in Clinical Neurology, may be interested in helping. Fortunately Dr. Jefferey rang me the very same day, expressed great interest in the condition and offered to help us by investigating the disease further, possibly by reviewing past and any current cases. He is also to willing to see any new cases but these must be referred to him in the normal way by a veterinary surgeon. I have since provided him with copies of the pathology reports from three of the UK cases, video tapes of the UK and Italian puppies and also contact details of the Italian and Dutch pathologists and neurologists. I am currently discussing with him the logistics of transporting the brain and spinal cords, from two affected pups, from the USA to the UK for histopathology at Cambridge University.

Those of you who attended the Health Seminar in 1999 may remember that, whilst watching the video of Teabag at the RVC, I mentioned that Dr. Targett had commented that he had been told by Dr. Simon Wheeler that he had found abnormalities, not just in the cerebellum but possibly in parts of the forebrain and long tracts of spinal cord. After I had sent a copy of the video of the Italian pups to Dr. Jefferey he said that some of the symptoms which the puppies displayed were not due to abnormalities of the cerebellum so there was definitely something else going on. Hopefully, if the UK, Dutch and Italian neurologists can collaborate successfully we may see CA fully identified in the not too distant future.

Added: 09/18/2005  Hits: 39528  Votes: 1  Rating: 

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