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.

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.