ARDS in Dalmatians

The author, dr. Tyge Greibrokk, has been professor of analytical chemistry at the University of Oslo in Norway since 1986. He is the head of a major research group, international editor of a scientific journal, he has supervised more than 100 masters and Ph.D. students and he is the author/coauthor of about 200 scientific publications, including papers on methods for DNA-analysis and one paper on inherited deafness among Dalmatians.

Introduction
Adult Respiratory Distress Syndrom (ARDS) appeared as a symptom of a genetic defect (ref.1) among Dalmatians in Finland (and once in Denmark) in the years 1987-1997. In Finland 6 litters were affected, the last in 1997, with a total of 17 dogs thought to be suffering from the disease. All the 17 dogs died or were euthanized. Early on, indications for an inherited disease were found by dr. A.-K. Järvinen and coworkers in Finland and studies of the pedigrees of the affected litters soon pointed towards the bitch O´Soul Escada as the probable source of a genetic defect. The damage to her genes is thought to have been caused by a point mutation. Several of the descendants from Escada were extensively used in breeding and the results (concerning ARDS) appeared to be in accordance with an autosomal recessive mechanism of inheritance. Although there has been no test matings to ultimately prove this mechanism, the national breed clubs in Finland, Norway and Denmark and the health committee of the Danish Kennel Club have accepted the recessive inheritance hypothesis based on strong circumstantial evidence.

A study utilizing simple statistical metods for estimating the number of affected dogs that would be expected in Finland, starting with the first litter after Escada in 1977 (the O´Soul K-litter), ending with all the litters registered in 1997, including all the litters in between (in Finland) supported the hypothesis of a recessive inheritance (ref. 2).

Probability of inheriting the defect gene
A dog which has inherited the recessive defect gene is called a carrier. A carrier cannot become ill, unless both parents carried the bad gene. If a carrier is mated to a non-carrier, the probability for a puppy of inheriting the bad gene is 50% (1/2). Since we in most cases do not know who the actual carriers are, we can only talk about statistical probabilities for inheriting the defect gene. This means that in the next generation (the 2. generation after a known carrier) the statistical probability for being a carrier is 1/4, in the 3. generation 1/8, in the 4. generation 1/16, in the 5. generation 1/32, in the 6. generation 1/64, in the 7. generation 1/128 and so on. All this assumes that the other parent is outside the ARDS lines. Thus, from the 7. generation on, the probability of being a carrier is less than 1%.

A recessive gene in the population will by constant “dilution” (mating each new generation with non-carriers) soon become no health problem, as long as new carriers are not produced. As a matter of fact point mutations are quite common and a national population may contain many defective recessive genes, which are not known, appearing only by extensive in-breading. This is the reason why small populations are bound to give genetic problems and why it is important not to reduce the genetic variation more than absolutely necessary.

Probability of provoking the disease
Recessive inheritance means that the illness can only be caused by parents both carrying the disposition for the defect. In average, 25% of the puppies (1/4) after two carriers will become ill, 25% will be free of the gene, while 50% will inherit the gene without becoming ill. It is important to be aware of that this is the statistical average of large numbers. Thus, in a small litter it is very likely that no defects will be found. The way of calculating the statistical probabilities of provoking the disease, in mating two dogs which both have an ARDS background, is to multiply the two probabilities. If a 7th generation dog is mated with a 6th generation dog, the probability of provoking ARDS is 1/128 multiplied with 1/64, which is close to 0.01%. For all practical purposes this is outside the danger zone.

Recommendations to the breeders
In 1993 the discussion of means to stop the ARDS threat, spread from Finland to Norway and Denmark. The breed clubs made some preliminary recommendations, until further knowledge could be obtained. The author of this article, who by the way had no breeding on the ARDS lines, argued for taking rapid measures, in accordance with the expectations of recessive inheritance. The discussion soon centered on the potential losses by eliminating too many good dogs from breeding, versus the risk of spreading the bad genes. After extensive discussions with veterinarians that were familiar with inherited diseases, it became clear that the specialists would not give direct advice on exactly where to stop breeding, because they had little knowledge of other potential problems that could be provoked by limiting the population too much. Everybody agreed on, however, that parents, littermates and direct offspring of afflicted dogs should not be used in breeding. Further measures were left to the breed clubs to decide. The recommendations which finally were made, met no opposition when this author discussed the situation with geneticists at a conference of inherited canine diseases in UK in 1994. Later, when the situation had become less urgent concerning immediate measures, the recommendations (in Denmark and Norway) were strengthened in order to prevent new carriers from being imported.

Current rules/recommendations in breed clubs
So far the breed clubs in Finland, Norway and Denmark have rules/recommendations for their breeders on ARDS. The recommendations vary according to how difficult the situation was considered in each country. In Finland, carriers, littermates of carriers and the first generation of offspring are not allowed in breeding. In Denmark the same plus the second generation are not allowed. In Norway the same plus 3th and 4th generation are not allowed. In Finland the sum of ARDS-generations must not be below 10 when two dogs are mated. In Norway the sum is at least 13 and in Denmark it is at least 14. Thus, in Denmark it is allowed to cross two 7th generation dogs or i.e. one 3th generation dog with one 11th generation dog. In Denmark, imported dogs must not be closer than 7 generations after a carrier. According to the opinion of this author, more breed clubs could assist their breeders by making recommendations for breeding. Such recommendations should probably vary in different countries, according to the size of the potential problem. It is important that the information is balanced, not resulting in hysteria and war between breeders. Furthermore it should be made clear that it is up to the breeders how long the ARDS will continue to be with us as a potential problem. By continued breeding on dogs close to carriers, the ARDS threat will stay with us. By breeding away from the carriers, the problem can be solved in a few years, as demonstrated by the development in Norway. A country (breed club) without dogs on ARDS-lines, wishing to avoid the extra bureaucracy of keeping track of every generation, could follow the import restrictions of the Danish club.

Possibility of identifying a carrier
In theory it is possible to develop methods to identify the carriers by analyzing their DNA. However, the site of the bad gene on the DNA is not known, and blood samples from only a few afflicted dogs are available. Current methods cannot resolve the problem with this material, unless new research is directed towards developing more information. Unfortunately, such research is very expensive, probably too expensive for the limited resources of the breed clubs in Europe. The possibility of developing a DNA-test for checking the absence/presence of a carrier in the near future, is therefore not high. Consequently it would be wise to base new measures on the information which already is available today.

Getting information
That information is available from the Word Association for Dalmatians (WAFDAL). Dalmatian owners/breeders seeking the “ARDS-status” of their dog(s) may contact the author, with a copy of the pedigree(s). Some of the European Dalmatian clubs already have received the background knowledge and can also provide the same information on request.

References

1. A.-K. Järvinen, E. Saario, E. Andresen, I. Happonen, S. Saari and M. Rajamäki, Lung injury leading to respiratory distress syndrome in young Dalmatian dogs, J. Vet. Int. Med. 9 (1995) 162-168.
2. T. Greibrokk, Inheritance of the disposition for ARDS among Dalmatians, ECDC meeting, Kolding, Denmark, August 1999.

Follow the link to ARDS-tables for more information