The Doberman Heart
An estimated 60% of Dobermans will be diagnosed with Dilated Cardiomyopathy (DCM), which is a fatal disease. DCM has an average age of onset of 6-8 years old, but can develop at any age. There is no definitive test to determine if a dog will develop this disease in the future. DCM incidence in a dog's pedigree, along with confirmation that neither parent is already affected, are the far and away the best two tools we have to help us minimize the risk of producing puppies that might become affected by this condition. Every ethical breeder should have a recent, clear ECHOCARDIOGRAM and 24 HR HOLTER MONITOR done on their breeding pair. See the different sections below to learn more about DCM, the tests used to screen for it, how genetics play a roll, and how we incorporate this information into our breeding program. While genetic testing is a valuable tool, NO ethical breeder will call their dogs "cardio clear" based on DCM1/2 gene test results.
What is DCM?
Most Doberman DCM exhibits as left-sided heart failure. However, about 30% of cases exhibit arrhythmias which can result in sudden death. Early signs of the disease are subtle (gradual exercise intolerance and weight loss) and are very frequently overlooked or attributed to other causes. By the time a Doberman is overtly symptomatic (lethargic, coughing) the disease has already progressed to end stage and life expectancy even with medical intervention is short: days to weeks. However, if preclinical signs of DCM are found and supportive medication and monitoring are begun while the disease is still in the occult phase, affected dogs can expect many more months and even years of life before end stage DCM presents.
Tests for DCM
Because DCM can initially present in two different ways, via structural changes to the heart or via ventricular arrhythmias, it is important to screen for both. An echocardiogram directly measures heart morphology, and a 24-hour ambulatory electrocardiograph (Holter) checks for the presence of arrhythmias. It is recommended that every Doberman have both screenings done at least yearly starting at the age of two because by the time a dog shows overt symptoms, they have already sustained irreversible damage to the heart and their long-term prognosis is poor. Please see the DCM Genetics section below for more information about genetic testing.
DCM Genetics
Studies by Dr. Meurs, a veterinary cardiologist at North Carolina State University, found two potential genetic mutations that were initially believed to be strongly linked to a given dog's risk of developing the disease(1). Unfortunately, follow up studies have found that these two mutations are not the answer that Dr. Meurs had hoped for. Many dogs with copies of both mutations have healthy cardiac checkups their entire lives and pass away due to other causes at well past 10 years old. Additionally, quite a few dogs who have testing clear for both mutations have gone on the develop and die from the disease, sometimes at heartbreakingly young ages. The reality is that DCM is likely due to a very complex interrelation of both cardio-protective and cardio-destructive genetic mutations, and that DCM1 (PDK4) and DCM2 (TTN) gene test results do not accurately predict DCM risk at this time(2). No ethical breeder will call their dogs "cardio clear" based on DCM1/2 gene test results.
Additionally, a new study in Europe has identified two other potential DCM risk markers and cast additional doubt on the validity of the DCM1/2 markers(3). Because prior genetic markers failed to hold up to real world testing, the new genetic markers are specifically noted to not be causative or to eliminate all risk even in genetically clear dogs, and were found using only European dogs, we are not confident that these genes will prove to be any more predictive of DCM risk in the American Doberman population. The study's authors cautioned against eliminating any Doberman from the gene-pool based solely on these results, so we have chosen to hold off testing for these markers until it is available as part of the Embark testing panel, or if real world testing done by others substantiates the study's findings in the American Doberman population.
Additionally, a new study in Europe has identified two other potential DCM risk markers and cast additional doubt on the validity of the DCM1/2 markers(3). Because prior genetic markers failed to hold up to real world testing, the new genetic markers are specifically noted to not be causative or to eliminate all risk even in genetically clear dogs, and were found using only European dogs, we are not confident that these genes will prove to be any more predictive of DCM risk in the American Doberman population. The study's authors cautioned against eliminating any Doberman from the gene-pool based solely on these results, so we have chosen to hold off testing for these markers until it is available as part of the Embark testing panel, or if real world testing done by others substantiates the study's findings in the American Doberman population.
(1) Canine Dilated Cardiomyopathy - Recognition & Clinical Management. Kathryn M. Meurs, DVM, PhD. (2002).Waltham/OSU Symposium
(2) Assessment of PDK4 and TTN Gene Variants in 48 Doberman Pinschers with Dilated Cardiomyopathy. Kathryn M. Meurs, DVM, PhD, Joshua Stern, DVM, PhD, Darcy Adin, DVM, Bruce W. Keene, DVM, MS, Theresa C. De Francesco, DVM, and Sandra P. Tou, DVM. Journal of the American Veterinary Medical Association. (November 15, 2020, Vol. 257, No. 10, Pages 1041-1044)
(3) Identification of novel genetic risk factors of dilated cardiomyopathy: from canine to human. Niskanen, J.E., Ohlsson, Å., Ljungvall, I. et al. Identification of novel genetic risk factors of dilated cardiomyopathy: from canine to human. Genome Med 15, 73 (2023)
(2) Assessment of PDK4 and TTN Gene Variants in 48 Doberman Pinschers with Dilated Cardiomyopathy. Kathryn M. Meurs, DVM, PhD, Joshua Stern, DVM, PhD, Darcy Adin, DVM, Bruce W. Keene, DVM, MS, Theresa C. De Francesco, DVM, and Sandra P. Tou, DVM. Journal of the American Veterinary Medical Association. (November 15, 2020, Vol. 257, No. 10, Pages 1041-1044)
(3) Identification of novel genetic risk factors of dilated cardiomyopathy: from canine to human. Niskanen, J.E., Ohlsson, Å., Ljungvall, I. et al. Identification of novel genetic risk factors of dilated cardiomyopathy: from canine to human. Genome Med 15, 73 (2023)
Genetic Diversity
Inbreeding depression is a term describing the negative effects high levels of inbreeding can have on a population of animals. One such effect is reduced longevity: a recent study found a direct relationship between increased inbreeding coefficient and decreased lifespan. The genetic Coefficient of Inbreeding (COI) is a measurement assessing inbreeding in an individual. Embark vet is currently the leading veterinary laboratory to provide this measure. Genetic COI ranges from completely diverse/outbred at 0%, to completely inbred at 100%. As a reference, a sibling-to-sibling mating in a healthy, diverse population would produce a progeny with an approximately 25% COI.
Unfortunately, Dobermans are critically inbred on a breed wide level, with an average COI of 40%. Additionally, no registered purebred Doberman in the 3,000+ dogs tested through Embark and the Doberman Diversity Project have been found to have a COI lower than 20%. Piper and all Kickturn puppies have been tested through Embark and their COI results can be found here.
While lowering COI is an important consideration in breeding towards better health, it is only one piece. Indiscriminate breeding without consideration of health and longevity in the pedigree can do more harm than good. Read on below for more insights about how we factor in the need to conserve genetic diversity on a breed wide level, as well as improve genetic diversity within our own lines.
Unfortunately, Dobermans are critically inbred on a breed wide level, with an average COI of 40%. Additionally, no registered purebred Doberman in the 3,000+ dogs tested through Embark and the Doberman Diversity Project have been found to have a COI lower than 20%. Piper and all Kickturn puppies have been tested through Embark and their COI results can be found here.
While lowering COI is an important consideration in breeding towards better health, it is only one piece. Indiscriminate breeding without consideration of health and longevity in the pedigree can do more harm than good. Read on below for more insights about how we factor in the need to conserve genetic diversity on a breed wide level, as well as improve genetic diversity within our own lines.
How to lower COI Through Breeding
If the breed is highly inbred, how can you lower inbreeding? While overall the breed is highly interrelated, data collected through the Doberman Diversity Project found that individual Dobermans cluster into four population subsets that are more highly related to each other than to Dobermans of other clusters(4). Breeding across these subsets, while also keeping a close eye on overall pedigree health and longevity, in any potential breeding dog, will produce puppies with much lower COIs.
The four distinct population subsets in Dobermans Four genetically distinct clusters were found: American exhibition lines (a.k.a. "American show"); European exhibition lines (a.k.a. "Euro show"); European working lines; and informal lines (a.k.a. "pet"). A fifth cluster was also found and appears to be a hybridization of other clusters. Of these distinct population subsets, there are two whose health and longevity are generally tracked and considered in breeding choices: American show lines, and European working lines.
The four distinct population subsets in Dobermans Four genetically distinct clusters were found: American exhibition lines (a.k.a. "American show"); European exhibition lines (a.k.a. "Euro show"); European working lines; and informal lines (a.k.a. "pet"). A fifth cluster was also found and appears to be a hybridization of other clusters. Of these distinct population subsets, there are two whose health and longevity are generally tracked and considered in breeding choices: American show lines, and European working lines.
(4) A multi-dimensional scaling (MDS) plot showing the genotype-based clustering in PLINK can be found here. 48 individual dogs of known locale and purpose were used to identify each genotype-based cluster. Note: the lines I utilize are represented by the green (European working lines) and grey (American show/exhibition lines).
Individual COI vs Breedwide Diversity
In addition to the inbreeding of an individual dog, there is also the diversity of the entire breed's gene pool to consider. Unfortunately, the Doberman gene pool's diversity is as limited as it is inbred: most well-bred Dobermans are very closely related to each other. There are, however, a few lines found in some lesser-known populations that are relatively unique. We don't know yet whether these rare genetics are helpful (lines that escaped the genetic bottlenecks of the breed's history) or harmful (breeders may have incidentally bred away from these genes because of prior issues). But we do know from recent research that the less bottle-necked a breed's gene pool is, the better the breed's overall health and longevity.
Because the Doberman gene pool is so limited, healthy dogs that have uncommon genetics should be bred to limit further loss of genetic diversity on a breed level. Because there isn't enough data linking specific haplotypes to health outcomes, preserving uncommon genetics is not a focus of our breeding program. However, we still participate in STR genetic testing through UC Davis to contribute additional data points to the collective understanding, as well as follow with interest and support those who focus preserving the genetics of the breed as a whole.
For those who are interested, the UC Davis results for Piper and the entire "A" litter can be found here. It is interesting to note that both the sire (Keeper) and dam (Piper) of our foundation litter each carried a few less common haplotypes and our current breeding bitch, Rose, happened to inherit several of these less common haplotypes from each of her parents, making her more of a genetic outlier than we would have otherwise expected. Please see the Measuring COI & Diversity section below for more information.
Because the Doberman gene pool is so limited, healthy dogs that have uncommon genetics should be bred to limit further loss of genetic diversity on a breed level. Because there isn't enough data linking specific haplotypes to health outcomes, preserving uncommon genetics is not a focus of our breeding program. However, we still participate in STR genetic testing through UC Davis to contribute additional data points to the collective understanding, as well as follow with interest and support those who focus preserving the genetics of the breed as a whole.
For those who are interested, the UC Davis results for Piper and the entire "A" litter can be found here. It is interesting to note that both the sire (Keeper) and dam (Piper) of our foundation litter each carried a few less common haplotypes and our current breeding bitch, Rose, happened to inherit several of these less common haplotypes from each of her parents, making her more of a genetic outlier than we would have otherwise expected. Please see the Measuring COI & Diversity section below for more information.
Measuring COI & Diversity
As part of our commitment to health, we genetically tested our foundation bitch, as well as every Kickturn puppy through both Embark and UC Davis. There is a lot of discussion in the breed world about these two tests. Each uses its own methods and has its advantages and disadvantages. Below is a bit of information about them both.
Beyond testing for specific genetic traits, genetic testing can tell us more about levels of inbreeding in the dog itself, and the genetic diversity of a given dog compared to the breed population as a whole. The Doberman gene pool is quite limited because the breed was established using a limited number of dogs and has been further bottlenecked multiple times since by a variety of issues. Today the breed as a whole is in a genetically precarious position and we need to remain aware of continued loss of what genetic diversity remains. Genetic testing can allow us to see which dogs might carry genetic variation that is in danger of being lost in the breed. Below is a primer about genetic testing and it's roll in producing healthy dogs and a healthy breed population.
COI: The Coefficient of Inbreeding
Inbreeding is deleterious because many unhealthy and undesirable traits stem from recessive genes and doubling up on the same genes increases the chance that these recessive genetics can be expressed. To limit the level of inbreeding that occurs in a fixed genetic population, a metric called the Coefficient of Inbreeding, or COI, is used. There are different statistical methods to measure an individual dog's COI; it can be done with pedigree information or through genetic testing. In reality, true distribution of genetics can vary greatly from pedigree-based COI calculations that assume ideal averages of inheritance. To understand how COI is determined genetically, we need to understand the differences between the two ways of extracting DNA information: SNPs and STRs.
Genetic Diversity: Comparing Dogs and Preserving Genetics
Because the Doberman gene pool is already limited the breed is already seeing the effects of inbreeding with declining health across the breed. It is important to save what genetic diversity remains. How to best do this is a not clear cut, and each type of genetic test lends itself to different approaches. I do feel that Embark has one aspect that will be more helpful to the breed over time - extensive information about specific genetic variations paired with health information will give us far more opportunity to better understand genetic risk over time.
Beyond testing for specific genetic traits, genetic testing can tell us more about levels of inbreeding in the dog itself, and the genetic diversity of a given dog compared to the breed population as a whole. The Doberman gene pool is quite limited because the breed was established using a limited number of dogs and has been further bottlenecked multiple times since by a variety of issues. Today the breed as a whole is in a genetically precarious position and we need to remain aware of continued loss of what genetic diversity remains. Genetic testing can allow us to see which dogs might carry genetic variation that is in danger of being lost in the breed. Below is a primer about genetic testing and it's roll in producing healthy dogs and a healthy breed population.
COI: The Coefficient of Inbreeding
Inbreeding is deleterious because many unhealthy and undesirable traits stem from recessive genes and doubling up on the same genes increases the chance that these recessive genetics can be expressed. To limit the level of inbreeding that occurs in a fixed genetic population, a metric called the Coefficient of Inbreeding, or COI, is used. There are different statistical methods to measure an individual dog's COI; it can be done with pedigree information or through genetic testing. In reality, true distribution of genetics can vary greatly from pedigree-based COI calculations that assume ideal averages of inheritance. To understand how COI is determined genetically, we need to understand the differences between the two ways of extracting DNA information: SNPs and STRs.
- Embark' Vet uses SNPs. SNP testing can be done cost effectively on a broad scale across the genome and directly tests markers that remain stable over time. Genetic COI using SNPs to look at large swaths of genetic data pulled from hundreds of thousands of locations across the dog's genome and assess the number and length of "runs of homozygosity", or tracks of identical genetic markers that indicate inbreeding in the dog's pedigree. the runs of homozygosity to calculate genetic COI by considering hundreds of thousands of markers that remain largely stable over time, More information about Embark Vet's testing can be found on their website. This is currently considered to be the most precise approach to measuring COI outside of direct calculation from full genome sequencing, which is not yet commercially available.
- The UC Davis Veterinary Genetics Lab (VGL) uses the STR approach. STR testing is only cost effective on a limited scale, which severely limits how much data can be efficiently extracted. Despite this limitation, STR brings the advantage of providing more insight about relatedness and recent genetic changes because it focuses on genetic material that is much less stable and changes with each generation.
Genetic Diversity: Comparing Dogs and Preserving Genetics
Because the Doberman gene pool is already limited the breed is already seeing the effects of inbreeding with declining health across the breed. It is important to save what genetic diversity remains. How to best do this is a not clear cut, and each type of genetic test lends itself to different approaches. I do feel that Embark has one aspect that will be more helpful to the breed over time - extensive information about specific genetic variations paired with health information will give us far more opportunity to better understand genetic risk over time.
- Embark Vet's SNP panel has the capacity to see which dogs carry uncommon genes that the breed may be at risk of losing if a given dog isn't bred, but they do not make this information available to the end user with the philosophy that rare genetics shouldn't be a consideration in breeding choices because we don't yet know whether a specific version of a given gene is rare by happenstance, or is rare because it is associated with a health or temperament issue. While this is a valid point and would be reasonable in a population that wasn't already severely bottlenecked, such a stance doesn't allow us to preserve genetic diversity while science continues to seek better understanding of genetic variation. This stance also neglects to account for the reality that responsible breeders are already holistically limiting the continuation of deleterious genetics by considering the health, temperament, and conformation of every dog that they use in their breeding program. I personally feel that Embark is withholding important insights by not providing some sort of metric that compares how genetically similar a given dog is to the breed as a whole. While our ability to utilize this information remains limited, it is still important information to track.
- UC Davis Veterinary Genetics Lab's approach uses the STR method focused at points in the genome that have proven to be independent of physical and behavioral traits that breeders actively select for. They use the STR method to better understand relatedness in recent generations and compare it against the same points in the breed as a whole because they feel this indicates how inbred or unique a dog is relative to the rest of its own breed, rather than as a strict measure of inbreeding. More information about how the UC Davis Veterinary Genetics Lab developed the Canine Genetic Diversity test based on STR marker data for Dobermans here. I personally feel that, while there is value in focusing on nuanced relatedness within the breed, not all genetic diversity is automatically good diversity, and it is dangerous to lose focus on overall levels of inbreeding.
The Doberman Diversity Project
The Doberman Diversity Project partners with Embark in order to access participant's raw genomic data. This vast dataset is a priceless resource for researchers trying to help the breed's health. We submit all of our dogs and puppies' Embark test results as well as updated health test results, to the Doberman Diversity Project in support of their mission.
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HOW kICKTURN dOBERMANS UTILIZES GENETIC TESTING FOR GENETIC dIVERSITY
It is important to note that genetic diversity is only one aspect to consider in breeding towards better health without losing type or temperament. The health, longevity, structure, and temperament of the dogs in the pedigrees behind the breeding pair are all of vital consideration when making breeding choices.
Out of concern for the high levels of inbreeding found in purely show and working lines, we chose to cross our foundation bitch from American show lines with well documented health and longevity to European working lines with similarly strong pedigree health to try and help give the next generation of Dobermans the best chance for a long and healthy life. Additionally, we feel that such a breeding brings an excellent balance between form and function. Our future breeding choices will continue to consider genetic COI as one of the many aspects to balance as we strive to breed for better health, proper temperament, and correct conformation.
As mentioned above, we genetically tested our foundation bitch, as well as every Kickturn puppy through both Embark and UC Davis as part of our commitment to health. While we appreciate the value of using VGL's measure of haplotype frequency to directly compare individual dogs to the breed as a whole for purposes of preserving what is left of genetic diversity, we feel that inbreeding is best measured in absolute values using a genome wide panel such as Embark's because it considers a much larger portion of the dog's genome in its calculations than the specific markers used by VGL. Thus, we ultimately use the Embark panel to guide our efforts to reduce the level of inbreeding in the puppies we produce. Beyond contributing to collective understanding, we continue to test with UC Davis - VGL to stay aware of how our dogs relate to the breed population as a whole.
Out of concern for the high levels of inbreeding found in purely show and working lines, we chose to cross our foundation bitch from American show lines with well documented health and longevity to European working lines with similarly strong pedigree health to try and help give the next generation of Dobermans the best chance for a long and healthy life. Additionally, we feel that such a breeding brings an excellent balance between form and function. Our future breeding choices will continue to consider genetic COI as one of the many aspects to balance as we strive to breed for better health, proper temperament, and correct conformation.
As mentioned above, we genetically tested our foundation bitch, as well as every Kickturn puppy through both Embark and UC Davis as part of our commitment to health. While we appreciate the value of using VGL's measure of haplotype frequency to directly compare individual dogs to the breed as a whole for purposes of preserving what is left of genetic diversity, we feel that inbreeding is best measured in absolute values using a genome wide panel such as Embark's because it considers a much larger portion of the dog's genome in its calculations than the specific markers used by VGL. Thus, we ultimately use the Embark panel to guide our efforts to reduce the level of inbreeding in the puppies we produce. Beyond contributing to collective understanding, we continue to test with UC Davis - VGL to stay aware of how our dogs relate to the breed population as a whole.
Other Health Testing
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In addition to cardiac health and genetic diversity, it is important for breeders to test for other potential issues in the breeding pair. Dobermans are prone to and should be tested for:
The OFA is a public database for independently verified health test results. Completion and recording of all breed club recommended health testing with the OFA will earn a dog its CHIC certification. For Doberman Pinschers, CHIC certification also includes a Working Aptitude Evaluation (WAE). Piper was CHIC certified before she was bred and is retested annually to keep her certification current. Rose has completed all of the recommended health testing for CHIC certification but has not yet had the opportunity to go through the WAE. However, her yearly SAR certification considers temperament as part of the certification process and her lovely temperament is seen every time she is called to work. We believe transparency is an important part of responsible breeding and update our dogs' Dobequest Profiles with all of their test results regularly. We also request that puppy homes keep us appraised of any health issues so that we can have a full picture of the health of our lines. |
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