Interview June 2021

Question:
Thank you very much for taking the time to answer our questions, which we would like to publish with reservation to your agreement, so that more and more Akita breeders and enthusiasts deal with Gentetic Diversity.

Ph.D. Avila
Thank you for this opportunity to discuss genetic diversity in Japanese Akitas!

Question:
You have taken up the legacy of Dr Niels Pedersen, who set the milestone for genetic diversity in Akitas to improve and preserve the breed. There was an interview with Peter v. d. Lugt and Dr. Pedersen about 6 years ago. Do you share Dr Pedersen’s opinion, do you have a different opinion, or have there been any new developments, e.g. with regard to the inheritance of SA, combating autoimmune diseases?

Ph.D. Avila
I completely agree with Dr. Pedersen, and share his opinion that genetic testing is an extremely useful tool that should be used in combination with in-depth pedigrees in order to breed healthier dogs over time. Unfortunately, since Dr. Pedersen’s interview in 2015, there haven’t been many developments in terms of the genetic factors contributing to SA in dogs, but one thing is for certain: inbreeding increases the potential risk of development of autoimmune disorders such as SA. So again, a powerful tool breeders have to combat autoimmune disorders is genetic testing, which will inform the degree of relatedness of potential mates, which in turn will guide breeding decisions with the goal of maintaining and distributing genetic diversity within the breed.

Insights from the recent years

Question:
The VGL genetic diversity test for Akita has been available since 2015. The first phases with diversity testing and study phase are over, and you currently have data from over 500 breeding dogs in the VGL database. Are you satisfied with this number?

Ph.D. Avila
As of December of 2021, we have tested over 750 Akitas of different varieties at the VGL. Even though this number gives us a great picture of genetic diversity within the breed, the more individuals we test, the better. This is due to two main reasons: 1) we can estimate genetic diversity in a population more accurately by having genetic data on a greater number of individuals; and 2) continued sampling of dogs allows us to monitor genetic diversity trends in the breed over time. This way, Akita breeders can make informed mating decisions based on more current genetic diversity metrics.

Question:
Do you already see an improvement in genetic diversity and haplotypes in our breed?

Ph.D.Avila
According to our latest assessment of genetic diversity in the breed, published in 2019 (https://vgl.ucdavis.edu/canine-genetic-diversity/akita), Akitas show a relatively high level of inbreeding, more so the Japanese variety when compared to the American variety, possibly due to a founder effect. But the good news is that since then, we have tested 200 additional Japanese Akitas and genetic diversity metrics have remained fairly similar both for the STR loci across the genome as well as for DLA region. As explained by Dr. Petersen in his interview, the DLA region is extremely important for immune regulation; therefore, the goal is to maintain (and ideally increase) genetic diversity in this region in order to prevent the occurrence of autoimmune disorders in the breed. This indicates that breeders have been doing a good job in maintaining and distributing heterozygosity, both across the genome and in the DLA region, over time.

Question:
What do you think would be the next steps to (further) improve the genetic diversity together with VGL?

Ph.D. Avila
I believe it is important to continue testing Akitas in order to closely monitor existing diversity into the future, both across the genome and in the DLA region. This can be most accurately done with the use of interrelatedness (IR) scores from our genetic test, in order to mate dogs as unrelated as possible. Moreover, testing of STR loci across the genome and assessment of DLA class I and II haplotypes are needed to better balance and maintain genetic diversity and as a supplement to in-depth pedigrees. The goal for breeders should be to produce dogs with IR scores close to (or lower than) zero. Mates should be preferably selected to avoid homozygosity at any genomic loci or DLA class I and II haplotype, and mating of dogs with less common genomic alleles or DLA haplotypes is encouraged.

Different haplotypes

Question:
We see in your VGL statistics, 70 to 80% of the Japanese Akitas tested so far carry the four most common haplotypes of class 1 and the four most common of class 2. Or in other words: We have 4 haplotypes in DLA 1, which are present in 88% of all tested Japanese Akitas.

What to do when we are at the point when we can no longer mate to get different haplotypes in the puppies?

Ph.D. Avila
Dr. Pedersen says (and I agree) that a relative lack of genetic diversity (as is the case of DLA haplotypes in the Akita) is not inherently bad, as long as breeders are judicious in avoiding a loss or imbalance in the existing diversity. Genetic testing can guide breeders to slowly increase the frequency of less common DLA haplotypes, in order to balance the existing genetic diversity in the breed.

Question:
What advice can you give to breeders of the Akita breed?

Ph.D. Avila
As a geneticist, my advice to breeders would be to make use of the vaulable information provided by genetic testing in addition to pedigrees to make breeding decisions. This is especially important in breeds that have a high incidence of autoimmune disorders such as the Akita, since the genes in the DLA region are intimately associated with immune regulation.

Question:
Is there a more positive development for our breed in genetic diversity and can we hope for mutations, e.g. of new haplotypes that are not yet in the breed database?

Ph.D. Avila
Since the Akita is a relatively popular breed, the more individuals we test the higher are our chances of identifying additional autosomal and DLA alleles, albeit at lower frequency. This knowledge is potentially useful for breeders, who can use it to propagate these additional alleles across the population through informed breeding practices.

Future perpectives

Ph.D. Avila
This is difficult to predict, since diversity depends on several variables. But breeders need to keep in mind that it is essential to mate dogs that are as unrelated as possible in order to maintain and distribute genetic diversity in the breed. Additionally, testing as many individuals as possible would allow us to potentially find individuals with rare alleles within the breeding population, and thus increase the frequency of such alleles by including these individuals in the breeding pool.

Question:
What do you think about the following possibilities for our breed?

• Rebalancing genetic diversity
• Reducing homocytogy (breeding heterocytogy with careful selection of partners)
• Seeking new diversity in the breed
• Outcrossing with closely related breeds

Which possibility would make sense for our breed at this point in time? What should be our main goal at this point in time? Are there any other solutions? At what point do we have to start thinking about crossbreeding with another breed?

Ph.D. Avila
At this point in time, I believe the goal should be to maintain and distribute the existing genetic diversity within the breed. We have tested breeds in the VGL that are far less genetically diverse than the Akita, so I don’t foresee a grim scenario for the breed in the near future as long as breeders work together towards the goal I mentioned above. Outcrossing is a delicate topic, because there are breeders that defend this practice in order to increase genetic diversity, whereas other breeders are vehemently against it since it allows for the introgression of alleles that might potentially alter breeddefining phenotypes. However, as I said earlier, I don’t believe this should be a concern for Akita breeders at the moment.

Risk factors

Question:
In Dr. Pedersen’s interview, there was talk of expected certain haplotypes that could be associated with risk factors in terms of autoimmune diseases (as in the case of the poodles, for example). In relation to the small number of haplotypes in the Akita breed, can we say about 50% of the Akita population carry a risk? How do you think about it? Have you identified haplotypes that carry a higher risk?

Ph.D. Avila
Unfortunately I cannot answer this question at the moment, as it would require a more in-depth research on the genetics of SA in Akitas. According to Dr. Pedersen’s studies on Standard Poodles and Italian Greyhounds, approximately 50% of the incidence of autoimmune disease is heritable; the other 50% is influenced by other factors. We would be able to answer your question, and identify DLA haplotypes that are potentially associated with increased risk in Akitas, through a research study focused on answering these questions, as Dr. Pedersen did on Poodles and Italian Greyhounds.

Evaluated Akita with SA

Question:
SA has not a recessive inheritance, but a complex genetic disorder with polygenetic inheritance. How should breeders deal with the ancestors here? How should this influence their breeding? How would you as Geneticist act here as a breeder?

Ph.D. Avila
Here, I will refer to Dr. Pedersen’s answer to a similar question in his interview: “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“.

Decision criteria based on VGL Mating Calculator

Ph.D. Avila
The goal of the mating calculator is to help breeders choose dogs that are as unrelated as possible, in order to maintain and distribute the heterozygosity currently existing in the breeding population. Therefore, I believe that the second option would be better because this would indicate that these dogs are more unrelated than those in option 1, and would also introduce more haplotypic variability with the breeding. This is corroborated by the variability in phenotypic features between the two dogs, because genomic loci with greater genetic diversity across the breed can be associated with phenotypic variation among individuals.

Question:
How important is it to decrease genetic diversity below zero for our matings?

Ph.D. Avila
When is comes to genetic diversity metrics, both internal relatedness (IR) and the inbreeding coefficient (F) below zero indicate outbreeding and thus are desired. When it comes to internal relatedness (IR), results from our genetic test are extremely useful in selecting potential mates. Ideally, breeders should aim to produce puppies with IR scores lower than zero over time. This can be accomplished by testing breeding dogs and using their IR scores to assure puppies of equal or greater overall diversity. Additionally, an inbreeding coefficient (F) of zero indicates that a population is in Hardy-Weinberg equilibrium, or in other words, mate selection is entirely random. This is achieved in outbred populations.

Thank you very much for your answers and the possibility to make that interview with you.

Ph.D. Avila
It was a pleasure to give you that interview.