THE PRA – RESEARCH PROJECT ON HUMAN GENETICS AT THE BOCHUM RUHR-UNIVERSITY

Gabi Maue

The Progressive Retina Atrophy (PRA) is a hereditary eye disease which many breeds of dogs are suffering from. It can't be treated, is not curable, and in its terminal stage it leads to blindness.

First visible impairments, not noticeable to dog owners, are uneasiness in twilight or in dark rooms, because the vision ability in twilight can not longer adjusted. Furthermore, there is a dilation of the pupils and an unusually strong light reflection in the back of the eye. This is why the eyes of such a dog seem to be large and radiant, and this phenomenon is alarming when it occurs in daylight and sunny weather.

In the initial stage of the PRA, however, a dog would have a completely normal behaviour, especially in its familiar surroundings. In places that are unfamiliar and strange to him, his increasing uneasiness is often interpreted as a behavioural disturbance.

The PRA is a disease transmitted autosomally recessive (except for the Siberian Husky and Samojede – here the PRA is transmitted chromosomally and by Mastiffs autosomal dominantly).

Recessive transmission means that only in descendents suffering from this disease (afflicted with this disease) we can find defect-gene-carriers hidden in seemingly healthy animal-parents.Therefore, parents with only one defect gene-copy appear to be healthy and won't become diseased. But these defect genes are passed on to their descendents without being recognized.

Animals with only one defect gene are called carriers. Animals with two defect genes will become diseased – here we talk about marking carriers.

When two carriers mate, some of their descendents will be become carriers and marking carriers and eventually the outbreak of the PRA will manifest itself.

The location of the gene as well as the PRA producing gene vary in the different breeds. The point of the outbreak of the disease varies as well. There are breeds which show the first symptoms as a whelp, other breeds may show symptoms only after being 3-5 years old. The disease can only be reliable diagnosed with DNA tests.
As there are no DNA tests available for the most breeds, an early diagnosis is not possible. This being the case, a marking carrier can pass on this defect to its descendents without being detected and will eventually become also diseased.

Worldwide, it has not been possible so far to explain the disease more thoroughly nor to develop direct ( Irish Setter, Cardigan Welsh Corgi, PRA-type A, Zwergschnauzer, X-chromosal: Siberian Husky and Samojede) or indirect gene tests (Miniature Poodle, Engl. Cocker Spaniel, Labrador Retriever, Portuguese Waterdog and Chesapeak Bay Retriever).
With the help of those tests it is possible to recognize animals being the carriers of the PRA producing gene at a very young age. Only this way it can be avoided that diseased animals are used for breeding and the defect gene is passed on this way.

For many years, working groups in the molecular genetics field have been doing research work worldwide in order to find the PRA producing gene and thus enabling them to develop DNA tests for the various breeds. At the Molecular Human Genetics of the Ruhr University in Bochum, Germany as well, Prof. Dr. Epplen and his team are doing research work on the PRA mutation genes. This PRA research project is being financed by the Society for Kynological Research (GFK).
This institute works closely with the "Ophtalmology Circle (DOK) in Dortmund, Germany and the German Association for Dogs " Verband für das Deutsche Hundewesen” (VDH, Germany), also with Prof. Dr. B. Clerc, Vet. for Ophtalmology, Maison d'Alfort, France and with Prof. Dr. B. Spiess, Vet. for Ophtalmology, Zürich, Suisse.

In July 2000 the team in Bochum succeeded in discovering a new PRA – producing gene mutation of the Sloughis breed.
In the meantime, the Molecular Human Genetics in Bochum has offered a DNA gene test for this breed. Blood samples of the sick animals, as well as the blood of the parents, the litter and other afflicted animals were of great importance to the Institute. This success was greatly due to the commitment and concern of the breeders and the dog owners having sick animals.

I am myself the owner of a 6-year- old pedigree dog which became blind at the age of 3 because of the PRA! Trying to get the necessary cooperation for this PRA research project in Bochum, I had to go through a lot of trouble and certain factors made things quite difficult:
  • It is not very easy, even impossible to get the blood of the near related animals (parents and their litter), especially when the dog and its offspring are from abroad, as it is in my case.
  • Sometimes the breeder of such a dog won't give out any information.
  • A dog owner, for whatever reasons, may retain this immensely import piece of information to the breeders association.
  • Until the gene mutations for all breeds are found and the necessary gene test are developed, decisive measures for breeding can only be taken on the basis of such information!
  • Even the breeder's association – as it was in my case – is committed and supports this research project, "only” the members can be reached, but not the privately owned dogs.
  • Most of the owners of such dogs – the ones which have gone blind – don't belong to a breeder's association. They have neither access to the information about such research projects nor about the afflicted dog breeds published in magazines from the various breeder's association. This is surely a particular problem of the breeder's association, not only in Germany.

    Only a small percentage of pedigree dog owners are members of a breeder's association. The dealing with specific breeding problems could be carried out when more effectively if there was a flow of information from all pedigree dog owners. But on the other hand, there are a great deal of breeders who have ample experience at their disposal to be shared with private owners who don't belong to a breeder's association or club.

    For non-members it is now a question of getting over the inhibition level and to ask for advice and to pass on important information concerning the problems of hereditary diseases. Therefore it is not unusual for veterinarians to have more information and knowledge about the increasing number of hereditary diseases than the responsible breeders.

    If you should be the owner of a pedigree dog suffering from the PRA disease, you can support the work of the research institute and help fight the battle against the Progressive Retina Atrophy by participating in the research project.

    Please observe the following important factors:
  • The PRA disease ought to be diagnosed by a vet for Opthalmology and the test results to be corroborated.
  • Along with the corroborated results the Institute needs a DNA blood sample (5-10 ml EDTA blood) and a copy of the pedigree of the diseased dog.
  • Please ask your breeder to participate in the project with the mother dog (bitch) and perhaps with the father male, too.
  • Please ask your breeder to inform also the owners of the litter of your dog about the PRA disease and the research project.
  • It is advisable to inform not only the breeder of your dog but also the breeder's association in care.
  • A copy of the genealogical tree should be forwarded to the breeding association so that the necessary measures for the breeding can possibly taken.
  • Please inform the chairman of the breeder's association about your participation in the PRA research project.
  • Also inform your vet about the PRA project and ask him if you hang up a copy of this article in his waiting room of his surgery.
  • Furthermore, please inform other dog owners about the existence of this PRA research project. address:

    Tanja Schrameyer
    Human Genetics, MA 5
    Ruhr-University
    44785 Bochum
    Germany

    website

    DNA tests of the following breeds are being done now at the institute ( as of Febr. 2002):

    Breed (abbreviation) Total number of dogs Number of PRA-affected dogs
    Australian Cattle dogs (AC) 21 2
    Berger des Pyrénées (BDP) 43 1
    Berner Mountain Dog (BMD) 1 1
    Bolognese (Bo) 1 1
    Chesapeake Bay Retriever (CBR) 4 2
    Collie (Co) 4 3
    Dachshund (wire; D) 69 20
    English Cocker Spaniel (ECS) 12 6
    Entlebucher Mountain Dog (EMD) 27 17
    Golden Retriever (GR) 10 2
    Irish Setter (IRS) 3 2
    Labrador Retriever (LR) 144 5
    Miniature poodle (MP) 43 28
    Newfoundland (NF) 1 1
    Polski Owczarek Nizinny (PON) 1 1
    Rottweiler (Ro) 1 1
    Saarloos Wolfhond (Sa) 125 7
    Schapendoes (SD) 10 3
    Scottish Terrier (ScT) 1 1
    Sloughi (Sl) 188 5
    Tibetan Mastiff (TM) 3 2
    Tibetan Terrier (TT) 96 3
    Total 808 114

    The Institute needs about 5ml blood in so-called „ EDTA test tubes”. These test tubes, -un-chilled, with the name of the dog , a copy of the genealogical tree and the tests results of the eye examination, - must be mailed to the address mentioned below, possibly at the beginning of a week.

    When the blood is taken, it is not necessary that it be taken with the EDTA test tube as it needn't be sterile. As there is a vacuum in the EDTA test tube, the vascular wall contracts and this stops the blood from running.

    There are two simple methods which have been agreed upon with the Institute:

    1) The blood is taken with a normal syringe and must be transferred immediately.
    2) The vet removes the upper top of the EDTA test tube and lets the blood run through a tubule directly into the EDTA test tube.

    The participation in the research project is free of charge, except for the taking of a blood sample and the postal expenses.