Update polymyositis and Fit2breed

Update cooperation VHNK and the ExpertiseCentrum Genetica Diergeneeskunde (ECGG)

Polymyositis research (Dr. Peter Leegwater, Drs. Yvet Opmeer & Dr. Paul Mandigers)

There is some good news. We have found the mutation that can be associated with polymyositis. All the examined dogs with polymyositis have the mutation. This mutation can be found close to two important genes involved in the functioning of the immune system. Furthermore it is shown that Kooikerhondjes suffering from polymyositis have an abnormal function of these two genes. So the mutation no doubt has a meaning. However, not all the Kooikerhondjes with this mutation become ill. Kooikerhondjes that are homozygous for this mutation (they therefore have the two different alleles) have an increased risk, but not all of them will get sick. We see this more often with immune-mediated diseases.

Environmental factors or variations in the rest of the DNA can cause a dog to become ill or not. That is why we call this mutation a risk factor. Also heterozygous Kooikerhondjes (Kooikerhondjes with only one deviating allele) are also at risk. That risk is very small (probably less than 1 percent) but present. Since there are many Kooikerhondjes with this mutation, we see that about 1 in 3 sufferers of polymyositis is heterozygous (carrier) for the hereditary risk factor.

Pedigree research has shown that other factors are also involved. We noticed for example that in some litters several dogs got sick, which would not make sense if the mutation is only expressed in a small proportion of the Kooikerhondjes. However, if there is a variation in the DNA that makes a dog more at risk or less at risk, this explains what we see in some litters.

In order to investigate this factor the DNA of a group of heterozygous sufferers was compared to a group of homozygous sufferers which have remained healthy throughout their lives. This comparison led to signals on two chromosomes that have been further investigated. The first signal led to a DNA variant that seemed promising, but it turned out that it had a high frequency in the entire population. It was a false positive result that was a coincidental. The second signal could not yet be traced back to a variant in a gene. This investigation will be continued.


Improvement in the treatment of Kooikerhondjes with polymyositis (Dr. Paul Mandigers)

In recent years we have seen several Kooikerhondjes with polymyositis. In the early years of this study, the treatment results were downright disappointing. In most cases, a dog did not or hardly responded to the chosen prednisolone therapy. You expect this with an immune-mediated disease such as polymyositis. The treatment results did improve when we also treated with certain muscle supplements. Furthermore, based on the pathology result, we could also reasonably predict whether or not a dog would respond.

Thanks to the research by Dr. Leegwater and Drs. Yvet Opmeer (at the time a student), the hereditary risk factor was identified. Because the two genes immediately adjacent to this mutation functioned abnormally, we started treating Kooikerhondjes with a specific inhibitor of these genes. So far the results seem very hopeful.

Meanwhile, we have treated various Kooikerhondjes in different countries and some dogs recover in such a way that the owners report that they no longer notice something about their dog. A hopeful result! Of course the goal remains to combat the mutation, but given the wide distribution of the mutation this requires several generations.


Progress Fit2breed (VHNK)

At the moment a lot of progress is made with the development of “our” new app Fit2breed. Fit2breed will help us in the near future to breed healthy and social Kooikerhondjes in a responsible manner.

In the Fit2breed app pedigree data will be combined with DNA data. The app is being developed to provide the breeder with a tool in choosing a suitable partner for their dog. In the meantime, it is becoming an increasingly large project, many other breed clubs are showing interest and the Raad van Beheer is also considering a participation.

INPUT
Pedigrees
DNA marker
DNA tests
Population data
OUTPUT
List with suitable breeding males
Lower risk of health problems
Improvement of the genetic diversity
Limitation of inbreeding

At this moment various people are working with the data in the ECGG, choosing the most important data, converting the ZooEasy data to a version that is suitable for Fit2Breed. In close consultation with the information committee and the board of the VHNK, considerations are made, information and ideas are exchanged and input is given for further development. The structure of Fit2Breed as a company or foundation or ? also has to be chosen. This has to do with finances and here it is again very important, whether and to what extent major players such as the Raad van Beheer or Utrecht University participate.

One thing is certain, without the cooperation of the VHNK, the development of such a beautiful project would not have been possible in this time frame. This will also be reflected in the price. We have negotiated hard and owners of Kooikerhondjes will receive a special price. But here, too, no definitive answer is yet possible.

Collecting DNA samples

The next step for further development is now the collection of a large number of (sponsored DNA) samples. These samples are distributed from the VHNK for collection among recently used and soon available breeding animals. Within the Netherlands, a large number of owners have been approached from the VHNK with a request to collect DNA of their dog. Since DNA is already available from many dogs, the VHNK has made a selection for this.

In order to further fill the database, the VHNK will approach various stud owners in Germany, Denmark and Sweden with the request to take DNA from their dog. This selection is made by the VHNK and on the basis of already available DNA profiles.

Breeding regulations

The Club Breeding Regulations (VFR) were amended in the General Assembly of 11-05-2019 and have now been approved by the Dutch Kennelclub (Raad van Beheer).

It concerns the article about the behaviour certificate. This is necessary because ‘Vereniging Alpha’ now has a different name, namely ‘Vereniging van Gedragstherapeuten voor Honden’ (professional association for qualified dog behavioral therapists, formerly Alpha).
This has been changed in Article 1.7.

View the: amended breeding regulations

Notification polymyositis

The VHNK is happy to report on some important steps forward in the research around polymyositis.
A mutation has been found which is the cause off the illness. This means heterozygote and homozygote animals can be identified. However, this mutation does not cause all homozygote animals to become affected by the illness. As a result, the mutation does not differentiate between sick or healthy homozygote animals. Therefore, we cannot yet offer a DNA test that can specifically mark animals affected by the illness.

At present the laboratory of Utrecht University (UU) is engaged with genotyping all breeding-animals. When completed, this will give the necessary information to come to a constructive method to avoid breeding Polymyositis cases. As soon as the Fit2Breed app is ready for use, a risk assessment will be available in the app.

This research was supported by donations of Kooikerhondje clubs, breeders and individuals from all over the kooikerhondje-world. This project does not end with finding the mutation and the development of a risk assessment. Research will continue to find why animals do, or do not develop polymyositis. Therefore, it is important we continue to collect blood-samples of all breeding animals.
We are very glad about the collaboration with the University of Utrecht and will continue this into the future.

Fit2Breed App, estimated release 2020

We all have the purpose to breed dogs as healthy as possible. The breed clubs also have the purpose of maintaining the breed as a Nederlandse Kooikerhondje. To breed healthy dogs in a responsible and sustainable way, it is not only important to look at the individual combinations, but to consider the entire population.

A lot of data is already being collected, for example from clinical screenings for orthopedic disorders (Patella luxation) and eye disorders and the results of monogenetic DNA tests such as vWD and ENM. This data is often used on an individual basis to make male-female combinations and breeders use ZooEasy and the club register to look back on a number of generations of what occurs in their lines.
It would be a pity if breeders would not consider the clinical data when planning a mating.

At present, a source of concern for breeders is primarily polymyositis. We now know about this disease that at least one genetic factor is responsible for the occurrence, plus strong environmental factors or perhaps a second gene. In such a case you can no longer work with concepts such as “carrier” and “affected”, but we must proceed with a risk assessment for the proposed combination.

With the Fit2Breed project we also get SNP markers for the Kooikerhondje. These are small variations in the DNA that have many different applications. With these markers new DNA tests can be developed, but also parental determination, measuring genetic variation in an individual dog and combining parent animals (“genetic matchmaking”) are possible. The Expertise Centre Genetics of Companion Animals (ECGG) is currently working hard on developing the Fit2Breed software module. In addition to the Nederlandse Kooikerhondje, the Labrador Retriever (just in the Netherlands) is one of the two breeds for which Fit2Breed will be used first. With the Fit2Breed software it is possible to analyze all important data (disease data, results of screening examinations, risk estimates and breeding value estimates, results of monogenetic DNA tests and SNP data for genetic variety) and thus arrive at a scientifically supported breeding advice. For the breeder this means that he can fill in his female in the module, after which he gets a list of all males, sorted by suitability. It is also possible to enter a desired combination of a male and a female, whereby it is then indicated whether or not this combination is suitable. For the system to run as well as possible, it is very important that as much data as possible is entered into the system.

The Kooikerhondje, with all the data already collected and entered in the ZooEasy database, is very suitable for co-developing this software. Considering the overwhelming amount of known data for the kooikerhondje, a breeding program that uses only the pedigree data and calculates the mean kinship of animals, does not seem a suitable choice.