Breeding for a healthier future...
Auto Immune Disease
Autom immune disease has been a concern in beardies for as long as I can remember. In the past dogs died from 'kidney disease' or 'liver failure' and now we know it is probably these individuals may have been suffering from Addison's disease or Haemolytic Anaemia. Many more dogs had 'nail bed' infections and the truth is they were most likely suffering from one of the most common of the AI disease found in Beardies, SLO or symetrical lupoid onchodystrophy.
Auto immune disease is rare but Beardies, and many other breeds, have a predisposition to develop various forms. At the moment all we know is that several elements come into play when a dog develops an AI disease. There has to be a genetic predisposition but there must also be environmental factors that trigger the disease. If the environmental factor is not encountered even those dogs with the highest genetic predisposition will not go on to develop a health problem. The environmental factor is probably a virus or group of viruses but it could be any form of stress the dog encounters, from breaking a leg to coming into season or rearing a litter of puppies.
I was very pleased to attend the Kennel Club's 2012 Breeder's Symposium which covered aspects of genetics, DNA testing and breeding for health.
I was particularly pleased to hear Dr Lorna Kennedy, senior scientist at the Centre for Integrated Genomic Research at the University of Manchester. Dr Kennedy spoke at a Beardie Health seminar earlier in the year and someof her material related to Beardies. She has spent the past 20 years working on the Major histocompatibility Complex region of the genome in dogs and wolves. The MHC plays an important role in the immune system of all mammals and, as in humans, MHC associations have been indentified in most canine auto immune disease. Within the MHC there is a region called the Dog Leucocyte Antigen (DLA), a set of three variable polymorphic genes that are inherited from each parent. These sets are referred to as haplotypes and, in line with most breeds, Beardies have about five different haplotypes. Also in common with other breeds, one of these haplotypes is more common than the others.In Beardies this is haplotype 1 and is carried by more than 40 per cent of the breed. Haplotypes can predispose a dog to developing a particular auto immune disease but act as a 'protective' against it developing another. Haplotype 1, for example, is thought to be a risk factor for SLO but seems to be protective against Addison's disease. Haplotype 3 appears to carry greater risk for the development of Addison's disease and, in many breeds, haplotype 4 has been implicated with auto immune haemolytic anaemia.
Sadly all this information does not mean we can go test our dogs for their haplotype status, breed accordingly and live happily ever after.
The haplotypes do not work on their own but are affected by around 40 other genes and by all important environmental factors such as viruses. If a dog has all the genetic markers to predispose it to a particular disease but is lucky enough never to encounter the trigger factor it will remain healthy. And a dog with a haplotype that predisposes it to a particular disease but without the multiple other genes involved will also remain unaffected even if it encounters the virus.
Dr Kennedy explained that is was very unlikely that there would be a genetic test that would advise breeders on which dogs would produce AI disease. The most we can hope for is a test that will give a percentage risk of what a dog will produce. Percentages can be difficult to work with. A ten per cent chance of venturing out in the rain without a coat and getting caught in a shower might seem a much less risk than having one puppy in a litter of ten destined to suffer a dreadful disease. We might even find ourselves in the position of having to evaluate, for example, the risk of developing hypothyroidism, which is relatively easy to treat and manage and the risk of developing Addison's disease which, whilst manageable, can have more devastating effects.
Dr Kennedy emphasised the importance of maintaining all haplotypes. A common haplotype is probably common for a good reason - it give protection. A rare haplotype might be rare for a good reason, being detrimental to the dog. At the moment we don't know enough to take the huge risk of trying to eliminate any haplotype. It would probably be a good idea to breed dogs with a particular haplotype to dogs with an alternate set. However, testing is expensive and the best offer would be testing a batch of 100 dogs for around £5,000.
It is interesting that the same haplotype can have different effects in different brees. Although we should be working to make the best of our gene pool we must also consider the fact that introducing a 'new' haplotype might also introduce diseases that we currently don't have. In the same way, working to increase the incidence of a minority haplotype might have the unwanted effect of increasing the incidence of a disorder that is currently rare.
There may never be a DNA test that will identify the dogs most likely to produce auto immune disease. We may eventually have a test that will give us a 'percentage chance' of a particular dog developing a particular disease but even that is some years in the future.
What we can do is to adapt our breeding programme to ensure we make the best use of the genes we have available. We must work to reduce the average co-efficient of inbreeding within the breed. COI represent the likelihood of a dog inheriting identical genes from the same individual ancestor. In Beardies it is common to find a dog has 20 or more lines back to an individual stud dog of years gone by, 16 or more lines back to a second dog, 14 or more back to a third dog and so on. This gives the breed a COI that is higher than average and which we must work to reduce.
What Can We Do ?
The first and most obvious step is the reduce the use of popular stud dogs. The popular stud dogs of today are the high COI of tomorrow. In my opinion no dog should be used more than an absolute maximum of 10-15 times in its lifetimes, given the breed's annual rate of production of less than 600 puppies. Some stud dogs have produced well over 400 puppies in their lifetimes and this is simply unacceptable. They may be great sires of many champions but production at that level is harmful to the future of the breed as a whole. There isabsolutely no criticism of breeders of past years who have allowed their dogs to be used 40, 80 or even 100 times at stud. Knowledge evolves and as it evolves we must make use of it for the benefit of the breed we love.
Breeders should do their best to ensure the COI of litters bred are lower than the COI of the parents.
Some early lines in the UK have been underused and where these lines exist overseas it would be valuable to import them back into the UK.
Dogs affected by any auto immune disease should not be bred from. Matings that produce progeny affected by auto immune disease should not be repeated.
Breeders may need to consider the use of carefully selected working stock. If this is deemed necessary the dogs used must have every DNA test available and we must steer clear of obvious pitfalls such as using merles. A variety of dogs should be used to bring in a useful injection of new genes. Progeny should be mated within the existing KC registered gene pool for a minimum of five generations before application is made for them to become KC registered. Care must be taken to ensure that, as far as possible, the outcross dogs are kept in seperate lines. This will maximise their value when and if they join the registered gene pool. During this period ALL puppies produced must be DNA tested and checked for eye disease and other abnormalities. If any health issues become apparent the line concerned must be discarded.
We may never be able to eradicate auto immune disease but by ensuring our dogs have as wide a gene pool as possible we give them a better chance of being heterozygous - that is having different genes at the same locus. If one gene is faulty the chances are its 'pair' will be healthy and the dog will have a far greater chance of a healthy life. The big challenge to breeders of the future will be to maintain breed type at the same time as promoting a wider gene pool and consequent low COI. In my opinion the best way of achieving this will be to breed for 'type' without discounting dogs because their lines do not 'tie in' with those of the bitch.
Wendy Hines December 2012