By Peter van der Lugt

Nowadays, many Akita breeders and owners have been confronted with the nightmare called Sebaceous Adenitis. Also known as SA for short, this autoimmune disease has pretty much spread out to almost every corner of our breed. As its cause still hasn’t been determined, I thought it was good idea to have a short conversation with Dr. Niels Pedersen, who friendly accepted my request.

Dr. Pedersen is an expert on SA & genetics with an immense track record, and used to be responsible for the Veterinary Genetics Laboratory and the Center for Companion Animal Health at UC Davis. Even though he is sort of retired now, he still continues to do research full time. He was recently involved in a research on SA and Addison's disease in Standard Poodle and currently spends his time on a valuable research on genetic diversity in Akita. The latter is a project that is still open to receive DNA swabs of more dogs—so please join in—but more on that later.

Several examples showing the clinical symptoms of sebaceous adenitis in japanese akita inu

Several examples showing the clinical symptoms of sebaceous adenitis in japanese akita inu

When talking to Dr. Pedersen, he eagerly offers some basic, but important advice on how to combat SA.

“The main thing that Akita breeders must do is to stop fighting with each other as to who has the purest dogs, stop denying that DNA testing is of no value and that pedigrees provide all of the information that is needed, and to actually contribute to the research monetarily, with good health data, and with DNA samples. Most researchers grow frustrated by their inability to get the kind of help that they need. Breeders cannot complain about researchers not doing their job when they do absolutely nothing to help projects succeed. There are many researchers studying SA in various breeds, including Akitas that fail for lack of help. We also need a lot better cooperation on our basic genetic diversity testing, which is essential for helping to understand heritable health problems in the breed.”

I mention him that, even though the cause of SA still hasn’t been confirmed, there are researchers that note SA “appears to be inherited as an autosomal recessive trait”, which in my opinion is a misconception.

“The inheritance is definitely not as an autosomal recessive with partial penetrance as many breeders have believed. It is definitely polygenic and could involve many genetic polymorphisms, each contributing a very small amount of risk, and none of which is absolutely essential for disease. These polymorphisms appear to be ancient in dogs, as SA has appeared in a number of breeds in combination with other autoimmune conditions. The more inbred a breed or an individual, the more concentrated risk factors become, and the more likely you will see autoimmune diseases like SA.”

Currently the only diagnostic test available for SA is a skin biopsy evaluated by a dermatopathologist. Because the age of onset varies and some affected dogs are "subclinical" with no outward signs of disease, SA is an especially challenging problem for breeders. This is why (in the US) Standard Poodles used for breeding should have a yearly biopsy, something that is not being done with Japanese Akita. I ask Dr. Pedersen about this way of preventive screening.

“Yes, it is always a problem dealing with a disease that often does not appear before a dog has sired or birthed many litters. SA usually appears before 7 years of age, but some are even older when diagnosed. Therefore, the biopsy program used in Standard Poodles does not make complete sense. By the time a dog becomes positive it may have produced dozens or more offspring of various ages, so what do you do with them? Do you just repeat the same cycle of testing on their healthy progeny or do you eliminate all of their offspring from breeding even though many of them appear healthy and their skin biopsies are negative. Also, there are a lot of Standard Poodles that have subclinical disease on biopsy – they show lesions in the skin but have no gross skin lesions. Most of these dogs never develop clinical disease, but rather remain outwardly normal. What do you do with these dogs? A better approach would be to identify families that have a high incidence of SA and to identify genetic risk factors that favor SA, such as certain DLA haplotypes, certain levels of inbreeding, etc. I doubt that a specific genetic marker for the disease that will identify carriers will ever be found, although it is still worth the attempt. SA is a disease of inbreeding, just like all autoimmune diseases, and the best way to deal with it is to increase genetic diversity."

We continue our talk about the background of the Akita, mentioning some of the bottlenecks like WWII, the breed split and impact of dogs like Ise Unryuu, as well as cultural differences that bring in challenges on solving things. Taking all of that into account, I ask Dr. Pedersen how he thinks breeders should fight this disease.

“I am well aware of the history of the breed and the problems that have existed between the various camps and ethnicities, but the time has come to work together. The first step is to identify all of the genetic diversity that exists in Akita, no matter the variety, in all parts of the world. We have taken the first steps in doing this with the preliminary diversity testing being done through the VGL that has now reached phase 2. This was not an easy study to do and there are still registries that have refused to participate in the study and more data to be collected. Therefore, the results that you see come from breeders and Akita lovers that have been willing to work outside of their registries and camps for the good of all Akitas.”

Of course, I am also interested in hearing about Dr. Pedersen’s view on how much risk people can take. If a breeding dog has known SA carrier in its pedigree, how many generations back would in his opinion be considered OK?

“These types of diseases are ancestral and may go back thousands of years in the process of dog domestication and evolution. If a disease occurs after a specific genetic bottleneck, like a popular sire effect, the pedigrees need to go beyond the bottleneck to be of any value. Three or five generation pedigrees are of no value if the bottleneck that brought in the disease occurred before these generations. Also, a pedigree is like a family history that provides knowledge about individual ancestors, i.e., was it a champion, where did its ancestors come from, how many puppies did it produce, etc. However, they are only a theoretical measure of genetic contributions, e.g., 1/2 ,1/4, 1/8, 1/16, etc. They do not take into consideration genetic recombination and any falsifications or mistakes that may have occurred. The only way to determine the actual genetic contributions of ancestors is to do DNA testing. That is not to say that pedigrees are of no value – both pedigrees and genetic testing based on DNA are important for a thorough study of a breed. For instance, we used both DNA testing and pedigrees extensively in our recent research publications on autoimmune disease in Standard Poodles and Italian Greyhounds. I would encourage people to go to the Journal of Canine Genetics and Epidemiology to freely download both of those papers.”

In this research Dr. Pedersen earlier worked on, it is mentioned that in Standard Poodles there is a strong link between its inbred population and SA. While personally not being the biggest fan of intensive line breedingpreferring to focus on keeping genetic diversity in the long termif I understand things correctly this connection does not literally say line breeding causes SA. I ask him for a bit of clarification.

“Breeders use the term “line-breeding” very loosely. A line is technically a subpopulation that is phenotypically and genotypically distinct from other lines. True line breeding would be to cross families of dogs that vary both phenotypically and therefore genotypically. Line breeding in the current sense is often used for crosses between Ms. Smith’s kennel in Boston and Mr. Jones’ kennel in London. Without knowing the genetics of a line and how they differ from other lines, line-breeding can be no more than outcrossing between closely related and highly inbred lines.”

Next to SA's genetic cause, I ask Dr. Pedersen about its famous external trigger and the influence it plays.   

"Well, we clearly stated in our articles on Standard Poodles and Italian Greyhounds that only about 50% of the incidence of autoimmune disease is heritable. This means that the other 50% is influenced by other factors. Epigenetics refers to genetic changes that occur after conception that occur either spontaneously or as a result of external influences such as exposures to infections, sex hormones (neuter vs. not-neuter), stress, natural radiation, sunlight, drugs, etc. The roles of these post-conception changes are evident in human identical twins. The older they become, the more different they appear in many aspects. Therefore, one twin can suffer from a certain set of diseases, whle the second twin develops different diseases."

Current SA treatment is focused on minimizing symptoms, instead of solving the cause of it. Even though a dog's DNA has already been handed out by its parents and therefore determines if he/she theoretically is high risk for SA, I can't help asking Dr. Pedersen if he thinks there is a way to avoid having it appear. Of course, that (sadly) was too much to wish for.

"No, at least not at this time – we have no knowledge of the specific genetic risk factors that predispose to diseases like SA (other than inbreeding) and we have little control over the epigenetic factors that affect how those risk factors will be expressed. Therefore, in almost all cases the “die is cast” at birth and we become spectators in subsequent events."

As I somehow remembered people claiming SA cases to actually be thyroid problems, I ask Dr. Pedersen about the most common misconceptions about this disease.

“I am not aware of this misconception, but it has a grain of truth. SA is a distinct disease entity, as is hypothyroidism. The latter is probably the most common autoimmune disorder in both dogs and humans, and it is the first autoimmune disease that tends to show up as a breed becomes more inbred. Therefore, it is not unusual for both conditions to occur in the same dog. The target of the immune system is the thyroid gland in one disease and the sebaceous glands in the other.”

While mentioning him about having heard of some differences in how SA presents itself in short and long coated breeds, I am curious if there are there any specific differences on how SA presents itself with Akita compared to other breeds that tend to suffer from it.

“SA is SA, no matter in what breed it occurs. The pattern of disease or its outward appearance may differ a little between breeds, but the basic lesions are identical. It is a difficult disease to treat, because some dogs respond to conservative topical therapies, others to immunosuppressive drugs, still others to a combination of topical and immunosuppressive drugs, some go into spontaneous remission, and some get progressively worse no matter what you do.” 

By now I have noticed Dr. Pedersen is genuinely focused on solving things together and generating a respectful debate. Everybody who is involved in this breed brings in his or her share, but it still makes me wonder about something, so I can’t help to ask him a more personal question. He shortly shares his feelings on breeders that know certain dogs have given complications in the past and continue making combinations with the same risk giving dogs sometimes even appearing 10 times in it.

"In answer to this question, which would appear to be more than theoretical, these are the types of breeders that ruin one breed after another. They have full faith in their own instincts and believe that the problems occurring from inbreeding are myths. What more can I say?"

Dr. Pedersen has mentioned he is currently working on a research on Genetic Diversity in Akita and that he has been somewhat disappointed by the small amount of entries till so far. I myself see enough valid reasons to participate, but I can imagine some people saying "We already know the genetic diversity of our breed is immensely limited. If we already know that, why should I join in?" How would he convince them? 

"The truth is that they do not really know how much genetic diversity their breed possesses. They know that the breed started with a limited number of founders, they know that there have been some artificial genetic bottlenecks such as a popular sire effect, and they know that their breed suffers from many chronic health conditions that appear to be heritable. Admitting that they have these problems and not wanting to know why they occur is an admission that nothing can be done, so why do anything. Many breeds that have been bred into genetic corners can be helped. Some may require a rebalancing of existing diversity, some may require reducing homozygosity by breeding for heterozygosity using careful mate selection, some breeds may need to search out new diversity from within the breed that they don’t know exists, and some may have to go to outcrossing to bring in new diversity. All of these courses of action require a detailed knowledge of the genetics of their breed based on pedigrees and DNA testing."

The first results of the same research have been published recently, and I must applaud Dr. Pedersen for their swiftness. While I would recommend everyone to take a look at the results themselves and keep an eye out for any updates, Dr. Pedersen summarizes the most important findings till so far.

"The preliminary baseline genetic data on the two main varieties of Akita and blends of the two have allowed a new insight into genetic diversity in the breed. Some of the information confirms what is historically known, e.g., AKA and AKJ are varieties of the same breed and were created from dogs originating from the same pool. The data also confirms that AKA and AKJ have lost a lot of the genetic diversity contained in their present day randomly breeding village dog relatives. The data, particularly on the AKA, show a pronounced positive selection for dogs sharing the same DLA haplotypes. This is probably the result of a popular sire effect. The data also demonstrated the ability to increase diversity to some extent by judicious crosses based on actual DNA based data within and between AKA and AKJ. The test procedures used to obtain this information provides an essential tool to search out more diversity, whether in other Akita or in closely related breeds and to provide the mechanism to integrate this diversity with the greatest efficiency and effect."

I bring up Dr. Pedersen's advice to fight SA by outcrossing the Akita with another breed. When looking at the history of our breed, in particular the restoration during the beginning and middle of the last century, we already know outcrossings took place, so it wouldn't be completely bizarre. For example, the pedigree of Dewa Go, one of the founding dogs of our breed, shows two interesting ancestors: Katsuhire Go a.k.a. Kappei Go (who was a Hokkaido dog) and Goma Go (who is said was a German Shephard). Furthermore, we know of breeds like the Chow Chow having played a role as well. Still, during recent conversations on outcrossing with Akita enthusiasts, reserved objections like "It will only bring in new problems & disease from other dogs" or "We will loose the type we have worked so hard for" and "We should look for the solution from within our breed" have not been uncommon. To end our conversation, Dr. Pedersen shares his opinion on this point of view.

"Well, I don't see why Akita breeders should be so concerned about outcrossing between the various varieties or even outcrossing to different breeds having a similar appearance. All dog breeds (and humans as well) are products of continuous outcrossing, backcrossing, and inbreeding for periods as long as millions of years and as short as a single generation. Why should such normal genetic manipulations be treated so abnormal? The goal is to have a dog with a certain look, function and behavior/personality. How you get to this dog is not the most important point, but rather how to maintain the full health potential of the species while creating this dog."

A FINAL MESSAGE:  One of the the ultimate goals of breeding an Akita dog is of course a healthy one. In a perfect world, the easiest thing to breed healthy dogs is to start with healthy parents, but this is exactly where the challenge arises: underneath the genetic surface of our dogs issues and risks are often hidden. And because we can't see those, the result is that clinically healthy parents sometimes & somehow end up giving puppies with problems.

For the people that aren't too familiar with genetics, the starting point is to take into account that genes come in pairs, of which dogs inherit one from their mother and one from their father. When looking at inheritance patterns, the simplest situation to describe is when a health problem is "dominant" and only takes one bad gene to express itself. Those problems are fairly easy to exclude and dogs having issues that are inherited this way aren't fit for breeding. However, some issues aren’t dominant and instead have a recessive component. They need two of the same to result into a successful “evil pair”. In that case, if a dog ends up being affected, both parents are always to blame. But if a dog ends up receiving only one problematic gene from its parents, then the issue won’t show up. The latter is of course beneficial to the dog itself (as it won't have that specific problem), but it still is a carrier, so when this dog is used for breeding it will transfer that one "evil" gene to a part of it's offspring.

As Dr. Pedersen noted earlier, SA isn't inherited in either of these ways. It is a complex genetic disorder with polygenetic inheritance, which means more genes are in play. The way I normally explain this is by comparing it to a puzzle. For the SA puzzle to be completed, a dog needs to receive the right amount of "SA-puzzle-pieces". When again taking into account that dogs inherit genes in pairs and receive one from each parent, that would mean both parents play a role in SA. These roles aren't necessarily evenly divided though, it could for example be that the father has more of these "SA-puzzle-pieces" than the mother does and therefore also pays a bigger contribution to the cause of a dog having SA.

After our interview, I mention my puzzle comparison to Dr. Pedersen. Appreciating the parallel, he interestingly adds "... there are enough risk pieces in the breed so that almost any mating is likely to produce a puppy that will be affected. Of course, dogs that have SA or that are closely related to dogs with SA will have many more risk pieces than dogs that are clear of SA for several generations and with close relatives. Such dogs are rare, however. If you breed them, the risk is even higher of producing puppies that might develop disease."

Either way, as there is no DNA-test yet available to determine anything like this, Akita breeders will remain struggling to find the right combinations, underlining the reasons for participating in aforementioned research.

A big thanks again to Dr. Niels Pedersen for willing to share his knowledge and spending his time on doing this interview. We both hope it will be interesting for Akita enthusiasts around the world and stimulate discussion to help improve our breed.