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COI and DLA I & II

A thorough look into Doberman genetic diversity.
This page is undergoing continuous construction. Please check back often for new information!
COI means coefficient of inbreeding. Carl Beauchat with the Institute of Canine Biology defines COI as "Inbreeding coefficient of an individual is the probability that both alleles at a randomly taken locus of this individual are identical by descent. Or in other words: the average homozygosity in an animal that is caused by ancestors common to both the sire and dam." COI simplified is "the probability of an animal inheriting two copies of the same allele from an ancestor". The lower the percentage the less inbreeding - identical alleles by decent- a dog has. The higher the number the more inbred the dog is. There are many ways to calculate inbreeding, but the most common methods are genetic testing and pedigree study. The main fault with using the pedigree method is not knowing exactly what genetic diversity there is. The fault with genetic testing alone is you don't know what dogs or bitches saturate the pedigrees. (FREE ICB course on COI here!)

Pedigree dogs and wild isolated populations make excellent case studies for genetics, diversity, and health. Both examples share a commonality; both have high genetic COI and low diversity. It is an accepted fact that inbreeding reduces health and longevity. Inbreeding. The gene pool becomes reduced and the risk of inheriting genetic mutations rises. Inbred populations have more infertility issues and  autoimmune diseases. Doberman are one of the most inbred of the breeds. A 2017 study calculated the average genetic COI of Doberman to be 43% (https://www.instituteofcaninebiology.org/blog/an-update-on-the-genetic-status-of-the-doberman-pinscher) with Embark Vet showing the current breed genetic COI at 36%! Embark marks genetic COI under 30% as "good". The lower the percentage the better. A higher percentage is correlated with increased risk of autoimmune disease and a shortened life span. Note; ALL beings have a COI. 

Genetic COI is one tool all breeders should be looking into when planning pairings and litters. High genetic COIs should be avoided when possible, but are not inherently a bad thing. It is one part of the whole picture. Breeding for diversity is just as important as breeding for the breed standard. A low genetic COI does not always mean a healthy dog, and vise versa a high genetic COI doesn't always mean a poorly dog. You can have a low COI dog that is riddled with illness from the day it came home and you can have a high COI dog that lives to be 18 years old without any major health concerns. Breeders should breed for the whole picture. A breeding that offers phenomenal genetics and working ability is a good trade off for breed average COI percentages. It is also fair to trade some give room with show traits for a lower COI breeding. Breeding is complex and never a simple black and white/ right and wrong answer.

"The bottom line is that an Embark genetic COI calculated from your dog's DNA is the Gold Standard of COI testing and gives you insight and accuracy not possible to get from a pedigree calculator  "
Picture
The above graph shows the COI of Jackson's Rise of the Phoenix as compared to the average of both the Doberman Pinscher breed and to the average all other breeds.
COI made simple: http://www.dogbreedhealth.com/a-beginners-guide-to-coi/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579366/
​https://www.thekennelclub.org.uk/health/for-breeders/inbreeding/
https://www.instituteofcaninebiology.org/blog/coi-faqs-understanding-the-coefficient-of-inbreeding

The consequences of inbreeding: https://embarkvet.com/resources/dog-health/oedipus-rex-inbreeding-its-consequences-and-its-quantification/
​
https://www.thekennelclub.org.uk/health/for-breeders/inbreeding/
​https://www.akcchf.org/canine-health/your-dogs-health/a-clean-bill-of-health.html
​
https://www.betterbred.com/2019/01/05/lets-talk-about-coi-and-other-estimates-of-inbreeding/
​
http://www.standardpoodleproject.com/What%20is%20COI.htm
​
http://abri.une.edu.au/online/pages/inbreeding_coefficient_help.htm
​
Inbreeding and loss of genetic diversity, study: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0202849
inbreedinglittersize.pdf
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inbreedinginfertilitystudy.pdf
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Cross-Breeding Inevitable to Preserve The Highly Inbred Norwegian Lundehund (study)
​https://www.researchgate.net/figure/Average-inbreeding-coefficients-in-various-dog-breeds-a-selection_tbl1_312671522
When looking at potential breeding stock it is best to pick the dogs with the lowest COI that have the fewest homozygous genes and are a stable representation of the breed. Those dogs do not need to be a show dog or working do to be a foundation for a breeding program nor do they need to be of "superior" status to be "worthy to breed. Those "tags" have only hurt breeds and breeds like the Doberman. We need stable dogs with good health. A low COI dog with good genetics that is within the breed standard is a good candidate for a breeding program, most likely more so than a dog of equal genetic value with a much higher COI. 

Keep in mind, breeding for genetic COI is preservation breeding. It takes education, it takes time, it takes planning, it takes a lot of effort to find the right dogs, the right pairings and the right balance. It's breeding better. Breeding strictly for pedigree, for the titles and for the show (show or working line only) is no different than breeding just for color or off standard traits; it can ruin a breed and leads to inbreeding and increased health issues. But when breeding for COI you can inadvertently bottle-neck or eliminate valuable lines. It's the same balancing act as before. Don't shun other lines or dogs, keep an open mind and be prepared to open your kennel to new dogs. That is how you save a breed!
DLA and Diversity
major_histocompatibility_complex_diversity_in_dogs___disease_associations_-_tuftsbg2009_-_vin.pdf
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Lack of diversity results in fewer genetics and poorer health as a general population. There are two classes used to track canine autoimmune diversity; DLA class 1 (DLA II) and DLA class 2 (DLA II). DLA stands for dog leukocyte antigen. When researching DLA you may come across another term, MHC. MHC stands for major histocompatibility complex. These two terms are interchangeable. "The MHC plays a critical role in the immune response system and consists of three regions: class I, class II and class III. DLA genes belong to the first two classes, which are involved in the regulation of antigens in the immune system. The class II genes are highly polymorphic, with many different alleles/haplotypes that have been linked to diseases, allergies, and autoimmune conditions such as diabetes, polyarthritus, and hypothyroidism in canines." What that is saying is MHC is responsible for much of the immune systems response to disease and illness. Limited diversity increases the risk of developing autoimmune disorders.

Doberman as a breed have limited haplotypes and haplogroups. We have lost much of the diversity that was once there, mainly due to inbreeding for favored kennels and dogs, often seen in show and working kennels.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152640/
​
https://pubmed.ncbi.nlm.nih.gov/12074709/
​
https://www.sciencedirect.com/science/article/pii/S1090023314005309
https://help.embarkvet.com/hc/en-us/articles/115000246234-What-can-you-tell-me-about-inbreeding-
https://cgejournal.biomedcentral.com/articles/10.1186/s40575-015-0026-5
https://www.researchgate.net/publication/6384000_Canine_DLA_diversity_1_New_alleles_and_haplotypes
https://en.wikipedia.org/wiki/Dog_leukocyte_antigen

The Show Dog Killed a Breed

Yes, show dogs and working line only kennels do have higher genetic COI and inbreeding ratios than pet line and crossbred lines. Studies show solid evidence that show lines have, in fact, bottle-necked the breed. "American and European Doberman suffer the same heritable disease problems, but their incidence may be higher or lower in American than West European Doberman depending on the disorder. For instance, American Doberman Pinschers have a higher incidence of heart disease, while European Dobermann have a higher incidence of eye disease. The incidence of many of these disorders is reportedly low in Dobermann from Eastern Europe, but this may indicate less accurate diagnosis and reporting. If true, it would suggest that the incidence of these heritable conditions is increasing with the increasing interchange of show quality breeding dogs between these regions of the world." (paragraph IV., A.) - http://www.doberman.gr/arthra/DCM_Testing.html
Doberman Breeding Philosophy: https://dobermanblog.com/doberman-breeding-philosophy/

​
"​The inbreeding of the breed and continuous use of a few popular sires paired with the hereditary problems of certain dogs resulted in an increased hereditary problems in North American Doberman population. Dr. Reinhard Haberzettl mentions 5 hereditary defects of the breed (see Table 1). He further mentions that the population of German and European dogs is currently similarly highly burdened with 2 hereditary problems as a consequence of the same bad breeding practices." - http://dobermanpuppyforsale.com/health.html

Common practice among many esteemed kennels is to only use what they deem the "best" dogs and bitches, often that translates into breeding titled dogs and their offspring together and among other titled families. Many times popular sires like AM. CH Cambria's Cactus Cash and IDC SIEGER Fedor del Nasi. IPO1, ZTP V1B were bred to their own relatives and bred often. This severely crippled the gene pool; promoting the use of only a handful of studs and breeding among relatives was accepted and highly encouraged among breeders. This practice was, and still is today, seen as "responsible" breeding. Science shows that practice is detrimental to a species overall health and survival. While inbreeding can have a positive effect on a breed/species, it should not be the accepted norm and should only be used when there is no other option.  Genetic diversity is the key to a stable breeding population and to the breed/species general well being. 

The Current Hapoltypes & Haplogroups in Doberman

I reached out to Embark Vet and requested a complete list of the haplotypes and haplogroups in the Doberman. Embark kindly replied and provided the complete list:
Valeria Amato (embarkvet)

"Jun 4, 2020, 4:05:27 PM EDT
Hi Kalee:

I heard back from our Science team. Here is the full list:
Haplotypes found in Dobermans:
A11a/419_MT
A11a_MT
A16/17/99/100_MT
A18/19/20/21/27/36/94/109/361_MT
A18/19/20/21/27/36/94/109_MT
A226_MT
A228_MT
A22_MT
A247_MT
A29a_MT
A361/409/611_MT
A381_MT
A388_MT
A408_MT
A427_MT
B102_MT
B121_MT
B1c_MT
B28_MT
B45_MT
B47_MT
B57_MT
B58_MT
B6/8/67_MT
B95_MT
C1/2_MT
C16_MT
C25_MT
C34_MT
C38_MT
C42/54/55_MT
C59_MT

Haplogroups:
A1a_MT
A1b_MT
A1d_MT
A1e_MT
A2_MT
B1_MT
C1_MT
C2_MT


Best,
Valeria
Valeria Amato
Senior Customer Support Manager
Embark Vet"

What is a haplotype? A haplotype is the group of common genes inherited from one parent. Why is this important? Haplotypes help identify the origin of a species and track lineage. (https://help.embarkvet.com/hc/en-us/articles/115000241313-How-does-Embark-determine-haplotype-) Haplogroups are common genes inherited from a group (or family). Haplogroups help us understand and track lineage and how a group has come to be. Both haplotypes and haplogroups are means to identity a dogs genetic origin and background throughout time.

Breeding for the Whole Dog

"New DNA testing doesn't only permit us to calculate the Genetic COI in a dog. It also provides critical information on DLA haplotype, mitochondrial DNA, and more insight into meaningful genetic diversity. Geneticists now understand how this information is just as important (and possibly MORE important) to the genetic health of a dog than are the individual disease test results. It may be that a dog with strong genetic diversity (revealed through new DNA testing) is more likely to enjoy not only better health but also longevity than a dog that may be weak in terms of genetic diversity yet "negative" for DNA mutations for single diseases. But we don't yet know. What we do know is that relying solely on DNA disease tests, especially those related to Dilated Cardiomyopathy (e.g., PDK4 or DCM1 and DCM2) or solely on diversity testing (especially if based on a smaller number of genetic markers which can inadvertently speed the loss of genetic diversity) is likely an ineffective and potentially dangerous way to approach breeding where longevity and genetic diversity is important. 

As such, The Doberman Diversity Project strongly advises that buyers and breeders consider disease-specific DNA tests in light of a dog's overall genetic diversity, conformation, temperament and pedigree/ancestral longevity. Doing so, and working with a reputable breeder who is transparent and open about the breed's genetic challenges, increases the odds that an individual dog or litter are stronger genetic contenders and better serves the BREED's health in the years to come, in ways we previously did not understand was possible."
https://www.dobermandiversityproject.org/diseases.html
The Doberman Diversity Project was created to assess and address the genetic diversity and poor health of the breed. The aim of the program is to test every Doberman possible searching for the rare dogs that may help revive the breed. Unfortunately, the breed as suffered extreme diversity loss and faces an uncertain future. The DDP has failed to provide a solution or education on what dogs to breed to and has remained silent on the matter. They are a screening tool and not educating breeders on creating and truly preserving diversity.

​"Over time, the Doberman gene pool has continued to dwindle through the rampant use of popular sires, the cumulative effects of unchecked inbreeding (including linebreeding), and dramatic bottlenecks due to the World Wars and political upheaval. Modern Dobermans -- whether in America, Europe or Asia -- are remarkably genetically similar to one another. Their close genetic relationships further concentrate the genetic mutations behind life-threatening genetic disease -- disease that is very serious and often cannot be effectively treated or cured." This means that all Dobermans regardless of pedigree, line, kennel, and origin are basically genetic carbon copies of each other and genetic diversity has been severely lost.

Outcrossing? Is it a Viable Option?

I am not shy about supporting outcrossing. I believe outcrossing done right, to breeds not prone to the same cardiac, eye, and cancers that plague Doberman, would benefit the breed. One risk of outcrossing with other breeds is it could potentially lose what the Doberman is. I believe crossing back to the breeds that helped establish the Doberman will help reduce any lost traits (if any), making it easier to cross back into the Doberman we all know and cherish.
​
Much like the LUA program that outcrossed to correct and reduce the rate of painful and often fatal bladder stones in the Dalmatian, an outcross program may help save the Doberman breed and allow for fresh, untapped lines to be worked into the diversity pool. Diversity can't be added without actually adding to the gene pool. You can't just create new diversity from the diversity we have now.

Let's speculate an outcross program is started and approved by the DPCA. How should it be done? I personally feel we should avoid breeds with VWD, PRA, and cardiac issues. We need to pair to dogs of compatible genetics/genomes. Selecting the best dogs genetically as well as health-wise is crucial. Second, you would breed to look at the dog physically, matching with breeds similar in build to the Doberman. Thirdly, you want to consider the temperament and working ability. You don't just want a dog to look like a Doberman, you want it to be ​a Doberman. Once you have established a solid base of dogs to cross between, you then start the tedious process of selecting which dogs fit the Doberman standard and your health/program aim and keep them back. You continue to selectively breed until you have worked back up to purebred Doberman (genetically testing as 98% and higher). Temperament testing and working ability can be assessed by professional trainers. It will take as little as 2-3 generations to get back to purebred Doberman, in appearance, temperament and conformation.

I firmly believe the key to saving the Doberman and preserving the breed is to create more diversity. How that is to be best done is the million dollar question! Outcrossing is the only way to introduce sustainable genetic diversity.

"As far as we are aware, there are currently no formal breeding schemes operating which aim to reduce or eliminate this common condition ... (DCM) ... from the Doberman pinscher breed. A genetic test would be very valuable as this would enable the detection and removal of affected individuals from the breeding pool. However, because the condition is so common in Dobermans, there is concern that removal of all affected individuals from the breeding pool might cause excessive restriction in the choice of Dobermans to breed from, and hence a reduction in the size of the breed’s gene pool with the risk that other genetic defects may inadvertently increase in frequency. Such problems could be avoided by out-breeding with dogs of other breeds." - ​https://www.ufaw.org.uk/dogs/doberman-pinscher-dilated-cardiomyopathy

Keeping Purebreds Purebred

Many fear a true outcross program would ruin the breed's integrity and "dilute" their purebred status. I want to see the breed preserved and thrive. I am passionate about maintaining the breeds integrity. Doberman are a unique and versatile breed. I feel there may be hope for the breed as long as pockets of lesser known or used lines are tapped into. Genetic diversity lies in unused pockets across the country and around the world. Maintaining the Doberman as we know it today is crucial to keeping the breed intact.  The key to keeping purebreds purebred is to find and use lesser known dogs. Pet lines and imports from smaller countries may offer invaluable genetic material. Those pedigrees are often snubbed by fanciers of champion dogs and champion pedigrees because they lack the thrill, name, and popularity found in show or working kennels. Working lines bred to show lines can help create diversity. Show lines bred to service lines, pet lines bred to working lines, American pedigrees bred to imports ... we still have some tangible room to work with! Keep in mind these pockets are only sustainable for a short time and eventually we must look at what is best for the breed ... and that is to introduce new genetic material.

How to Use Genetic Testing and COI to Really Breed Better

The term "Low COI" has now become a street term used to gain trust and boost sales, but what does "Low COI" mean? Low COI means the dog has a below the accepted inbreeding index. A true low COI purebred is a COI at and below 2%. A  dog can be called a low COI dog with a COI of 33% even though it's breed breed average COI is just a few points higher at 36%. In some breeds, those minute percentages make a huge impact (such as in the Doberman) while in others it doesn't really matter as much. Regardless, it is best to maintain the lowest COI possible while preserving and breeding for the whole dog.

What makes a Doberman a "low COI" Doberman? The breed average COI is 36%, with many lines (especially European lines) creeping into the 50s! There is no definitive definition of "low COI" for the Doberman breed. It's an umbrella term used to describe dogs that have lower inbreeding ratios than the average. Any dog under 36% is technically a low COI dog. I classify a dog with a COI below 40% as a low COI Doberman. Ideally, the lower the number the better! I prefer to see dogs as close to 20% as possible. Unfortunately finding Doberman at and below 20% is extremely rare. When those dogs are paired with other Doberman their offspring are still high COI, with the ratio increasing with each generation, not lowering or maintaining.

When breeding for COI alone you will run into litter COI estimates still being high. This is because two low COI dogs can still be so closely related that they produce a higher COI litter. This is why it is important to use breeder tools that help you estimate the COI of your litter and why you should breed for the whole dog. Breeding is a trade off; there is no perfect litter. Your litter may be free of genetic mutation (carrier status) but have a higher COI, or a low COI status and have more carrier genes than you'd prefer or not have the exact conformation you wanted. Either way, breeding requires careful planning ahead of time. 

How do you breed for low COI? You research your lines. You know your pedigrees. You pair dogs that are unrelated genetically and pedigree-wise. Use the data given to you in you Embark or other breeder genetic panels. Use the maternal and paternal haplotypes and haplogroups and pair for as much diversity (differences) as you can get. Don't settle for a dog just because of convenience. 
It is crucial to note that genetic COI breeding within the Doberman is limited and unsustainable. The breed's genetic COI, even if a low COI Doberman, is too high to maintain a functional breeding pool. There are not enough genetics to preserve the breed for the future. The ideal way to create diversity is to create a universal outcrossing program closely monitored by conservation specialists. This would allow scientists to identify genetically valuable dogs and maximize their breeding potential. A professional outcrossing program is on the horizon and can soon become a reality!
Genetic diversity and morphological characterisation of three turbot (Scophthalmus maximus L., 1758) populations along the Bulgarian Black Sea coast - https://natureconservation.pensoft.net/article/64195/

Slow Recovery from Inbreeding Depression Generated by the Complex Genetic Architecture of Segregating Deleterious Mutations - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558994/
​
The effect of genetic bottlenecks and inbreeding on the incidence of two major autoimmune diseases in standard poodles, sebaceous adenitis and Addison’s disease - https://cgejournal.biomedcentral.com/articles/10.1186/s40575-015-0026-5

A Spectral Theory for Wright’s Inbreeding Coefficients and Related Quantities - https://www.biorxiv.org/content/10.1101/2020.10.07.329755v2.full

At a Crossroads: The Impact of Genetic Testing on Breed Diversity_purina_pro_club.pdf
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todays_breeder_dna_testing___genetic_diversity_tb100_sm.pdf
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doberman_pinscher_autoimmune_thyroiditis_screening___purina_pro_club.pdf
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​ Doberman Pinscher Update, Nestlé Purina PetCare
genomic_and_phenotypic_effects_of_inbreeding_across_two_different_hatchery.pdf
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_400__perrier_molecular_ecology_2017_do_genetic_drift_and_accumulation_of_deleterious_mutations.pdf
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how_genomic_selection_has_increased_rates_of_genetic_gain_and_inbreeding.pdf
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    • Fawn and Blue Doberman
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    • Heterochromia: Two Eye Colors
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