Genetic Testing
There's a LOT of information out there...
We understand this is a lengthy read, but we ask that all prospective families read this page prior to inquiring about our puppies.
Boxers can be prone to certain health conditions that can be scary and devastating to a family. But what are these health conditions and what can we do to mitigate the risks of developing these disorders in our beloved pets? Primarily we hear a lot about cancer, DM and ARVC. In recent years, we have also been hearing a lot about genetic screening to detect these diseases or the risk potential for these diseases in our dogs. There is a LOT of information (and MISinformation) out there, and it can be confusing and overwhelming.
Arrhythmogenic Right Ventricular Cardiomyopathy, or ARVC, is a primary heart muscle disease characterized by abnormal ventricular rhythms. The disease is so common in boxer dogs that it is often called Boxer cardiomyopathy. Common clinical signs are exercise intolerance and syncope. Many dogs have no outward clinical signs, but some may suddenly die. Fortunately, thanks to advances in genetic testing, there is a genetic screening test to detect the gene responsible for this disease and it is possible to avoid breeding two affected dogs together, which avoids producing puppies that could ever be affected. Our sire and dams have tested negative for the gene responsible for ARVC, therefore, no puppy we whelp will ever be affected by this disease.
The testing for DM is not as clear cut.
Degenerative Myelopathy, or DM, is a progressive neurological disorder that affects the spinal cord of dogs. Dogs that have inherited a specific and unknown group of genes will experience a breakdown of the cells responsible for sending and receiving signals from the brain, resulting in neurological symptoms. The disease often begins with an unsteady gait, and the dog may wobble when they attempt to walk. As the disease progresses, the dog's hind legs will weaken and eventually the dog will be unable to walk at all. Degenerative Myelopathy moves up the body, so as the disease progresses, the dog will eventually be unable to hold its bladder and will lose normal function in its front legs. Fortunately, there is no direct pain associated with Degenerative Myelopathy. The onset of Degenerative Myelopathy generally occurs later in life starting at an average age of about 10 years. The average lifespan of a Boxer is 10-12 years.
DM cannot be diagnosed without a necropsy (post-mortem autopsy). There are many things that mimic DM that are not DM. Despite what many breeders say, currently there is NO "test" that truly predicts the likelihood of developing DM in Boxers.
We were unfortunately convinced by others into believing there was a specific genetic test to determine if our dogs carried the “DM gene”. After our first litter, we had the genetic testing done on our sire and dams, and were deeply upset to learn that our dogs were either considered “carriers” or “at risk” for this mutation. What we were NOT told by other breeders, or by the genetic testing services we used, is that the SOD1 gene (what they consider to be the DM genetic test) is only a small piece to the genetic puzzle that is DM. We were NOT told that the genetic test does not test for a “DM gene” specifically, but rather for a mutation that has been found to be present in dogs with DM (the SOD1 mutation), and is present in many more healthy dogs that never develop DM, and even present in breeds that are not ever diagnosed with DM. DM is a polygenetic inherited disorder, meaning there is more than just the SOD1 mutation needed to inherit the disorder, and those genes are currently UNKNOWN.
Determined to get more information about this genetic screening before we made the permanent decision to alter our dogs and no longer produce puppies, we reached out to an expert in the field.
Jerold S. Bell, DVM is an Adjunct Professor of Genetics for the Department of Clinical Sciences at the Cummings School of Veterinary Medicine at Tufts University here in Massachusetts. He is also the chairman of the Hereditary Disease Committee for the World Small Animal Veterinary Association, a Director at OFA - The Canine Health Information Center, and is a well-respected DVM at Freshwater Veterinary Hospital in Enfield, CT. To say he is an expert in the field of canine genetics is an understatement. His credentials speak for themselves. We asked him about the current genetic testing for DM. His unedited response is as follows:
“The issue with degenerative myelopathy (DM) is that there is a gene (sod1 mutation) identified that must be present with two copies (homozygous) to have clinical disease. However, DM is a complexly inherited disease involving more than one gene pair. Compounding the fact is that the sod1 mutation is the most common mutation found in dogs, with 7.8% of all mixed-breed dogs and 5.4% of all purebred dogs carrying the gene. In some breeds, the frequency of the sod1 mutation is over 90%, though no members of the breed have been pathologically confirmed with the disease.
OFA sod1 test stats have 49.5% of Boxers testing homozygous "at risk".
In the only clinical study by Dr. Roy Berghaus at UCDavis (summarizing the breed frequency of DM at 26 US veterinary school hospitals between 1990-1999), 0.59% of all Boxers were clinically affected.
This would make a homozygous "at risk" sod1 test result in a Boxer only 1.2% penetrant. In other words, only 1.2% of all Boxers with a homozygous "at risk" result would be expected to become clinically affected with DM and 98.8% of Boxers with a homozygous "at risk' result would never develop the disease.
This makes a homozygous "at-risk" sod1 test result in a Boxer to be poorly predictive of developing clinical degenerative myelopathy.
There is ongoing research to try to determine the other genes that a dog must have to develop clinical disease. One gene variant in Pembroke Welsh Corgis in the SP110 gene increases the chance of developing clinical DM, but this mutation has not been found in other breeds.
The issue for Boxer breeders is how to use the sod1 test results to make informed breeding decisions. Selection against 81.2% of all Boxers (49.5% homozygous "at risk" and 31.7% carriers) would leave only 18.8% of the breed available for breeding. The breed cannot lose over 80% of its gene pool and survive as a viable breed. Uniform selection against the sod1 mutation should not be done until other genes causative of DM in the breed are identified.
While degenerative myelopathy is a devastating disease, it is a rare disease in the Boxer breed affecting less than one out of every 100 dogs. However, there are breeders with higher frequencies of clinical DM in their dogs due to the accumulation of the other gene or genes necessary to cause clinical disease. The results of homozygous "at risk" sod1 testing should only be considered if there are close relatives in the pedigree with pathologically confirmed cases of DM. In these cases, there is high risk of carrying the other mutated genes necessary for the development of clinical disease and causing the homozygous "at risk" sod1 result to be more predictive of clinical disease.
I hope that this information is helpful to you. I hope that additional mutations in the breed are identified (research ongoing at UMo) to provide a more helpful genetic test for breeders.
Jerold S Bell, DVM
Adjunct Professor of Genetics
Department of Clinical Sciences
Cummings School of Veterinary Medicine
Tufts University, USA
Chairman, Hereditary Disease Committee
World Small Animal Veterinary Association
Director, OFA - The Canine Health Information Center
Freshwater Veterinary Hospital
Enfield, CT USA
Tel 860-749-8348, Fax 860-749-4760
http://vetprofiles.tufts.edu/faculty/jerold-bell “
We are happy to forward his email directly to anyone who would like to review it.
We almost spayed and neutered our dogs based on well intentioned, albeit inaccurate, information being shared by breeders, none of whom were experts in genetic sciences or specific genetic testing for Boxers.
Attempting to actively breed away from this end-of-life and painless disease, without knowing all the genes that truly cause it, could in fact be harmful to the breed. If you actively breed out this particular mutation, you could be unknowingly breeding in a higher prevalence of far worse mutations.
We understand that this is complicated information, and we are always willing to answer any questions or concerns you may have regarding this testing, and if we cannot answer your questions, we encourage you to reach out directly to Dr. Bell at Tufts.
We also understand if this deters you from choosing one of our puppies as your new furever companion, and that's ok. We strive for total transparency with all of our families, and share any and all relevant, and even irrelevant, information prior to sending our puppies home. Our gorgeous dogs have wonderful temperaments, and have no known close relatives in their pedigrees with pathologically confirmed cases of DM. We cannot make guarantees about the lifetime health of our puppies, nor do we feel any breeder truly can. We can guarantee that our puppies (and their parents) are raised in a happy home surrounded with love and receive excellent veterinary care up until the moment they leave us. We can also guarantee our puppies will leave our care in good health. Until better testing is available, we believe that the benefits of continuing our breeding program far outweigh the risks of our puppies ever developing this disease. A diverse genetic pool is far more beneficial to the Boxer breed than to eliminate over 50%-80% of it.
If you are interested in reading further, here are links to other articles we have found:
Maneuvering the Maze of Genetic Tests: Interpretation and Utilization