Lhasa Apso Association of Wales & South West
As at 30th April 2002 the total donated to the Lhasa Apso Breed Council PRA Fund was £5552.32.
NEWSLETTER FROM DR. DAVID SARGAN
University of Cambridge
Department of Clinical Veterinary Medicine
To Mrs Pauline Torrance of the British Lhasa Apso Breed Council
Unfortunately the late onset of this particular form of PRA means that some dogs will inevitably have been certified as clear in these tests which will later become affected. Thus 26 is a minimum number of affected animals, whilst eyetests must be repeated every year. The disease is believed to be an autosomal recessive condition: this means that to be affected by the disease a dog has to inherit copies of the PRA mutant gene (causing the condition) from both its father and its mother. Working backwards from the proportion of eye tested dogs which are affected, one can calculate the proportion of Lhasa Apsos which carry the PRA mutant gene. Unfortunately it appears that this
may be as high as one third of all these dogs.
Testing for PRA: Eye tests and DNA tests.
How are we to get rid of this scourge? Eye tests are a first essential: clearly animals which are affected with PRA should not be bred from, and nor should their parents. The problem is that PRA is a late onset disease - so you have usually bred from a dog before you realise it has PRA. Worse than this, the affected dog's parent are likely to be towards the end of their breeding lives before they are withdrawn. So eyetests by themselves are not sufficient. What we need is a reliable way to detect those animals that will be affected with PRA before they show symptoms, and also to detect those animals that have the potential to father or mother PRA affected animals, before they are bred from. Analysis of a dog's DNA has the potential to provide such a test, if the mutation that causes PRA can first be identified. Such testing uses a small blood sample, or sometimes a salivary sample, from the test animal, and makes a specific analysis of the gene which carries the mutation. Test are 100% reliable and the result does not change over the life of the dog. Best of all, carriers of the disease (dogs in which a single copy of the mutant gene is present) are detected by these tests. These dogs will have normal eyes, but when carriers mate together 1/4 of their offspring will
have 2 copies of the mutant gene, one from each parent, and these dogs will suffer from PRA.
DNA tests are being applied to PRA in 2 breeds already: the Irish setter and the Cardigan Welsh corgi. In both breeds eye testing (combined with test matings) had been used to reduce the disease with some success in this country, but in both there had not been complete elimination of carriers of the disease here, and resurgences of the disease had occurred abroad and could occur here. This is despite the fact that in these diseases affected pups can be detected by eye test within 4 months of birth: a much easier situation for control than pertains in the Lhasa Apso. Mutations causing these diseases (different for each breed) were uncovered in my laboratory and as a result DNA
testing programmes for each breed are now available (in the case of the Irish setter, run by the AHT), and we are well on the way to entirely eliminating both diseases worldwide.
Finding a mutation and developing a DNA test.
BUT, (and this is a big but) before we can develop such a test we have to find the mutation causing the disease. The DNA which encodes all the instructions to make up a Lhasa Apso (or come to that, the DNA that makes you or me) is a long string of 4 different chemicals ("bases") the order of which specifies the information in the DNA (just like the order of letters in a sentence determines what we read). Just as a sentence is broken into words, so the information in the DNA is broken into genes, each of which supplies information for one protein. There are about 100,000 genes in the DNA and over 3,000,000,000 bases. A change in just one base causes the PRA mutation in each of the 2 breeds mentioned above. In each case it is a different base in a different gene. Thus the trick is to find the mutation. Techniques do exist to help us do this, but it is still a very big and complicated job, needing several (2-3) man years of effort (and a modicum of luck) for each disease tackled. Even with this amount of effort, we can only hope to succeed if we have blood samples from quite a number of PRA affected animals (at least 10, preferably more) and IMPORTANTLY, also from their parents and their brothers and sisters.
Once the mutation has been found, development of a useful DNA test is usually fairly straightforward and can occur in a matter of months. Once a test is in place there is one further requirement. This is that breeders take it up and use it.
Using DNA tests.
A DNA test will tell you whether your dog has two copies of the normal gene (Normal dogs); one normal copy and one mutant copy (Carrier dogs); or two mutant copies (Affected dogs). It is then up to you as breeders, through the auspices of the Lhasa Apso Breed Society to decide how to use this information.
"What can I do to help now?"
The Cambridge Vet School lab has applied for funding to search for the gene causing PRA in the Lhasa Apso, and some work has already begun. When we are fully funded this research will become the full time project of a postgraduate student who we hope will gain their PhD whilst finding the mutation and developing a test, but we wish to continue work immediately.
To continue the study we need owners of Lhasa Apsos affected with PRA to send us 2ml blood samples (taken "into EDTA" by their veterinary surgeon) to the address below. Even more important, we need them to trace the parents and siblings of the affected dogs and pursuade their owners also to send us blood samples from these dogs. In each case, we need the name and registration number of the dog, and its relationship to the affected dog. Fuller pedigree
information would also be very valuable.
We will not (at least initially) be able to tell owners of sibling dogs whether their dog carries PRA, since these samples are to do the research to allow testing to be developed. (Parents of Affected dogs are by definition carriers of the disease). But we will keep all of you informed of progress to
the goal of test development, and hope we will be able to announce a test within a fairly short time.
Please send blood samples to
Dr David Sargan
Centre for Veterinary Science
Department of Clinical Veterinary Medicine
University of Cambridge
Cambridge CB3 0ES, UK.