by C.A. Sharp
Should dogs with two copies of the MDR1 mutation be bred? How about those with one copy? These are questions many breeders are wrestling with. In some countries, regulating authorities have established rules that breeders must follow. Others are considering them. What is a reasonable approach to dealing with this mutation in the breeds where it has been found?
The MDR1 mutation needs to be kept in perspective. It is a mutation which can lead to reactions to some drugs whether one or two copies of the mutation are present; those with only one copy react at a higher dose than those with two.
Drug reactions are not unusual. Every drug has limits that define how much must be given to be effective in treating an illness and how high the dose can go before it starts causing unwanted side-effects. In chemotherapy agents the “enough” and “too much” overlap; the effective dose will cause side effects and sometimes very bad ones. But if the disease being treated is fatal when untreated, as with most cancer, enduring the side effects – even with the possible risk of a fatal result – may be the best alternative. It is also well known that some individuals react to some medications less well than others, this reaction may be that the drug doesn’t do what it is supposed to or does it less well, or the individual may have side effects that the great majority of people taking the drug don’t have. Many of these differences in drug reaction have a genetic basis. The MDR1 gene is one of the genes that can cause a reaction, as its original full name implies: Multi-Drug Resistance 1. There are probably many, many more genes that may cause reactions to certain drugs in dogs but we don’t know what they are yet.
Having the MDR1 mutation is a problem if you don’t know it is there. If a dog with even one copy of the mutation receives too much of certain drugs it can make the dog very sick or even kill it. But dogs have survived for millennia without these drugs and for at least a century – before the development of many of our modern drugs – some dogs have survived with the MDR1 mutation with no ill effect. In a wild animal which don’t go to the vet this mutation would have null effect.
Finding this mutation is a great boon to veterinary medicine: For some drugs the veterinarian can now know ahead of time that there could be a bad reaction and she can select another drug. For so many medications this option does not exist. No dog will go untreated because of the MDR1 mutation; it is a matter of personalizing the treatment to the individual dog, something that is now receiving great attention in human medicine.
The MDR1 mutation isn’t desirable but so long as testing of dogs in the affected breeds is standard and owners take a few basic precautions there need never be a dog that is lost to a drug reaction to those particular drugs because the veterinarian didn’t know there was a risk. We can’t say that for most drugs. Most breeds and mix-breeds have to take their chances when receiving medication because they have no similar test for whatever gene forms they have that can cause reactions.
So, what should breeding policy be? This mutation is a fault; it can have serious consequences if not dealt with appropriately. It is also an extremely common mutation in some breeds. In the case of Australian Shepherds fully half of the breed has at least one copy. You cannot eliminate half of a population from breeding without risking serious consequences to the gene pool. If your local laws or club and registry rules allow it, dogs with two mutations should be bred only to clear-tested mates; puppies with only one mutation will have a much reduced risk of reactions. Dogs with one mutation ideally should be bred to clear-tested mates as well, but in breeds where the mutation frequency is so very high this may be difficult to do. It may also be difficult if the breed population in your country is small. Making breeding decisions based on the status of one gene over all others only risks allowing other things, including other health issues for which we have no genetic screening, to become a greater problem. However, when dogs with a single mutation are bred, wither to each other or to dogs that have tested clear, all offspring should be tested and preference given to the best of the clear offspring of that cross to carry on with. In time the frequency of this mutation can be significantly reduced, but it must be done over a number of generations not overnight. Doing so will avoid creating bigger problems with diseases that are serious and complex in inheritance.
The MDR1 mutation should not be ignored. In breeds where the frequency is high (Australian Shepherds, Miniature American/Australian Shepherds, Collies, Long-Haired Whippets, McNabbs, and Silken Windhounds) every member of the breed and every mix-breed that has or is believed to have a high percentage of any of these breeds should be tested so its status is known. The test results should be shared with every veterinarian who ever has cause to treat the dog. The potential effects of this mutation can be totally avoided by responsible owners and veterinarians. Responsible breeders can reduce the frequency of the mutation over time without discarding quality dogs. That cannot be said for cancers, immune-mediated diseases, and even things like hip and elbow dysplasia, which all have a genetic basis, have no genetic tests, and can cause misery and even death to dogs both purebred and mixed.