But there have been ‘ups’, with both the ARVC and JKD research. A few days ago I visited paediatric cardiologist Robert Hamilton from Canada who was attending a cardiology conference in Wales and got an update on his bio-marker for ARVC. In a remarkable piece of outside-the-box thinking he had come up with an idea for detecting the presence of the disease before it was overtly recognisable. He had tested it out on number of his ARVC patients and all showed positive. Then he turned to Boxers affected with this same heart disease. All affected Boxers (American) also showed positive while a sample of UK Boxers, deduced by pedigree to be free of the gene responsible, proved negative. More intriguingly, but in a separate study, several dogs from a further UK sample, including some that were seemingly totally normal, although at risk by pedigree of carrying the gene, showed weakly positive suggesting they carried the gene and the test was offering an early diagnosis.
Finding this bio-marker represents a stunning discovery and it has since been probed and checked. The human work, supplemented by the main Boxer result, have been submitted for publication in a top American medical journal. I believe I have got it right when I say that only 40% of papers submitted to this journal get through the first editorial stage and go out to formal review. Dr Hamilton’s paper cleared this first hurdle immediately and I have great expectations for full reviewer acceptance as I think this a major milestone in human, and also Boxer cardiomyopathy research. For both species it opens up the possibility for a pre-clinical test which will serve virtually as a gene test for the disease. Much work still needs to be done to ascertain how early in life, and how effectively it picks up dogs which carry the gene but are apparently normal still needs to be ascertained; further investigation is needed.
For this further Boxer work, a first requirement is funding, and application has already been made to the AKC (about $50,000 is needed) and, given its importance for American breeders, I would hope that the ABC will step in to help. The second very obvious requirement is full breeder support without which nothing can be done. Here about 50 new affected cases will be needed plus a like number of clear-by-pedigree controls, plus as many close family relatives as possible, all with pedigrees (in total confidence). Breeders interested in helping would best contact me (email@example.com) in the first place. But no work or even sample collection will start until after the needed funding is obtained. In conclusion, the opportunity to get a sound working test for ARVC is now possible, but it is entirely up to Boxer breeders to help with the needed investigations. I do hope there will be major breeder support as an ARVC test is desperately needed in NA and, I’m afraid also in the UK.
Developments with JKD research are equally exciting. I wrote earlier about Professor Amos’ new findings, and progress continues He is quite confident that he has found the chromosome on which the gene for JKD lies, this indicated by an association between the disease and two of his micro-satellite markers on the chromosome. Moreover they mark the site to a small region in the chromosome where a number of genes lie, mutations in which could be responsible for the disease. He is now working through each of these genes, sequencing them for mutations. One gene has been eliminated and results on a second should be available by the end of November, and so it will continue until the gene with the causal mutation is found. If a mutation cannot be found then it all gets difficult; the mutation may lie in an inter-genic or regulatory region, which would make it very hard to find, but let’s hope for something simple.
Interestingly, we hear that the Swedish and Norwegian work has now also found what they believe is the location of the gene, and discussions on the possibility of all researchers working together henceforth are now in progress. However, although the Scandinavian interests are currently focussed on the diagnostic aspects of the work, any future collaboration will depend on agreement by everyone on the candidate region. Nobody is offering this information yet, and there are also practical problems to be resolved such as the partial duplication of material caused by the AHT contribution of swabs from UK dogs with the blood samples I sent to Norway earlier. With or without any collaboration this could bias the Scandinavian GWAS results. But it is all very exciting and illustrates the commitment of all researchers and their confidence that JKD has a basically simple inheritance. Professor Amos is still eagerly accepting swabs from affected normal dogs, and may be contacted directly for swab kits (firstname.lastname@example.org).