Why a Dog with a Single Copy of the MDR1 Mutation Shouldn't Automatically Be Removed from a Breeding Program
The MDR1 (Multidrug Resistance 1) gene mutation is a well-known genetic factor in dogs that can influence how certain medications are metabolized. While the mutation has gained attention, it’s important to understand why many experts, veterinarians, and breeders believe that carrying a single copy of the mutation should not automatically disqualify a dog from a breeding program. Here, we’ll explain why we believe a responsible breeding program should not exclude dogs with a single copy of the MDR1 mutation and how genetic testing and informed breeding practices can help maintain breed health.
The MDR1 gene encodes a protein called P-glycoprotein, which plays a crucial role in removing toxins and medications from a dog’s body. When a dog has a mutation in the MDR1 gene, it may have difficulty metabolizing certain drugs, leading to an increased risk of toxicity. Some medications, such as ivermectin (commonly used in heartworm prevention), some chemotherapy drugs, and anesthesia, can build up in a dog’s system if it carries the MDR1 mutation.
The mutation is particularly common in certain breeds, especially those with herding backgrounds, including Collies, Australian Shepherds, and Long-Haired Whippets. This shared role on the farm helped lead to the initial awareness of the mutation in dogs. Farmers who treated livestock for parasites, unknowingly exposed their dogs to much higher concentrations of the drugs through medicated feeds or droppings from treated animals. While the mutation is prevalent in these breeds, it is important to note that not all dogs with the mutation will experience severe reactions to medications.
Oh no, here comes the science. I'll try to not get too sciency, however we are talking genetics so it's impossible to completely cut out the science talk. Simply put, a puppy gets one copy or variant (known as an Allele) of the MDR1 gene from each of it's parents. When talking about mutations, if a dog is homozygous, it means they have two of the same gene - either both the mutated version or both the normal non-mutated version. On the other hand, if a dog is heterozygous, they have two different versions of the gene with one being mutated and the other being normal.
Most people are familiar with the concept of genetic dominance, where a dominant trait or mutation will overwrite or hide the recessive trait. The MDR1 mutation however is referred to as being incompletely dominant. With incomplete dominance, rather than one dominant gene completely covering up the other recessive gene, the two mix together to create something in between. For this reason it is inaccurate to refer to a dog with only one copy of the MDR1 mutation as a “carrier” as some people do, because traditionally, the term “carrier” implies they will exhibit no signs of the associated trait.
Genetic testing not only provides insight into an individual dog's genetic makeup, it also enables us to track how these genetic traits express themselves over time throughout the breed, offering a more comprehensive understanding of the overall genetic profile for the breed. In the case of MDR1, possessing a single copy of the gene has typically resulted in a markedly reduced expression of the trait, minimizing potential risks.
The presence of a single copy of the mutation does not automatically signify that a dog will experience adverse drug reactions. In fact, most heterozygous dogs are able to handle the medications in question, though they may face a slightly higher risk of dosage sensitivity compared to dogs without the mutation. Here are a few reasons why we feel a responsible breeding program shouldn't automatically exclude heterozygous dogs.
With proper veterinary care, the medication needs of a heterozygous dog can be safely managed through dosage adjustments or the use of alternative treatments. This careful management ensures the dog’s health without the need to exclude them from a breeding program.
It's worth mentioning that while drugs like ivermectin are commonly mentioned in relation to the mutation, the typical doses used for heartworm prevention are generally safe, even for dogs with two copies of the mutation. The concern arises when higher dosages are needed, as in the case of an infestation, where complications could occur if the mutation isn’t taken into account.
Experienced veterinarians, particularly those familiar with herding breeds, often adjust dosages or choose alternative medications with or without testing just to be cautious, understanding the prevalence of the mutation in herding breeds.
Modern genetic testing is an essential tool in any responsible breeding program. When it comes to MDR1, where homozygous dogs face a significantly higher risk of drug sensitivity compared to heterozygous dogs, genetic testing allows breeders to effectively eliminate the risk of producing homozygous offspring. This ability to manage the likelihood of dogs being at higher risk allows breeders to make thoughtful decisions, ensuring that dogs with a single copy of MDR1 can still be responsibly included in a breeding program. By carefully considering factors like genetic diversity and the overall health of both the breed and individual dogs, breeders can maintain the well-being of their dogs while making informed, ethical breeding choices.
Genetic diversity is essential for the health and long-term sustainability of a breed. By removing dogs with one copy of the MDR1 mutation from breeding programs, breeders risk reducing the genetic diversity within the breed. For breeds like the Australian Shepherd where roughly half the population possesses the mutation, eliminating all dogs with the mutation would mean eliminating half the gene pool. A decrease that severe in genetic diversity could inadvertently lead to the propagation of other genetic health issues.
Responsible breeders should strive to maintain a broad genetic base and carefully select breeding pairs based on a range of factors, including health, temperament, and overall genetic integrity, rather than excluding dogs based solely on the presence of a single mutation. In this way we minimize the risk of producing homozygous dogs (those with two copies of the mutation), while at the same time ensuring that healthy, genetically diverse populations are maintained.
While genetic testing is an important tool, it is just one aspect of a balanced, comprehensive breeding strategy. Responsible breeders take a more holistic approach, considering not only genetic testing results and their impact, but also factors such as overall health, temperament, conformation, and a dog’s ability to thrive in its intended role. A dog with a single copy of the MDR1 mutation should not be automatically excluded from breeding if it excels in these other key areas.
A responsible breeding program should prioritize the long-term health and well-being of the breed, focusing on the full range of traits rather than fixating on a single genetic factor. When bred with care and consideration, dogs with one copy of the MDR1 mutation can still make a meaningful contribution to the gene pool.
While the MDR1 mutation is an important consideration when breeding dogs, carrying a single copy of the mutation should not automatically disqualify a dog from being part of a responsible breeding program. With proper genetic testing, holistically based ethical breeding practices, and informed veterinary care, dogs with one copy of the MDR1 mutation can live healthy, productive lives. By maintaining a focus on genetic diversity, overall health, and responsible breeding, breeders can help ensure the long-term health and stability of their breed, without inadvertently propagating other genetic health issues or unnecessarily excluding valuable genetic contributors.
Breeding dogs is a complex process that requires a deep understanding of genetics, health, and the breed’s unique characteristics. By taking a well-rounded approach to breeding, we strive to produce healthy, genetically diverse dogs that will thrive in your home for years to come and contribute to the future of the breed.