.....::::: IRISH SETTERS IN ROMANIA :::::.....

CLAD stands for Canine Leucocyte (sometimes spelt Leukocyte) Adhesion Deficiency and is an inherited condition that exists in the Irish Setter population. The condition, first described clinically in the United States, is related to the same disease in humans (LAD) and cattle (BLAD). Affected pups die early in life from multiple infections, usually recurrent infections of the skin and bone marrow, even when treated with massively highdoses of antibiotics. This is a devastating inherited condition that leads to fatal immuno-deficiency. The genetics of the condition in the Irish Setter are known; it is caused by a single recessive mutation in a gene that is responsible for controlling a crucial aspect of white blood cell function. Because the condition is caused by a recessive mutation affected puppies must inherit two copies of the mutant gene, one from the dam and one from the sire. Since affected dogs do not normally reach sexual maturity, affected puppies are normally the consequence of a mating between two carriers of the CLAD mutation. The fact that CLAD is identical to a disease in manand cows has greatly aided the search for the CLAD mutation, because the genetic mutation causing human LAD and bovine LAD (BLAD) is known. This knowledge enabled a research group at the University of Uppsala in Sweden, led by Dr Leif Andersson, to show that the same mutant gene causes CLAD in the Irish Setter. They have now used this newly-acquired information to develop a DNA test for the mutant gene, a test that is being currently offered at the Animal Health Trust.The test is able to distinguish the mutant gene from its normal counterpart.

Remember:

* CLEAR dogs will have two copies of the normal geneand be clinically clear,

* CARRIER dogs will have one mutant gene and one normal gene and be clinically clear,

* AFFECTED dogs will have two copies of the mutant gene and be clinically affected. So, how does an individual get one of their dogs tested? You will need to get a "DNA Test Request Form" from the Animal Health Trust. The form requires the name and Registration number of the dog, its microchip or tattoo number (if applicable) and asigned declaration by the owner. This signature is crucial because an important part of this declaration is that the owner agrees that the result of the test on the stated dog be made public. The owner then submits the request form together with a blood sample that has been taken by a veterinary surgeon. Once the blood sample is returned to the Animal Health Trust it is processed in the laboratory to produce a DNA sample that can then be analysed. Once this analysis is complete a certificate is issued stating that the dog is either CLEAR of, or a CARRIER of CLAD. A copy of the certificates issued will be sent to The Kennel Club and used to maintain a database of clear and carrier Irish Setters. It is intended that this regularly updated data base will be readily available to all Irish Setter owners/breeders so that they can use the information when thinking about breeding programmes. Why is testing important? The main value is that it unambiguously identifies carriers of the condition, dogs that are clinically clear and will never develop CLAD but who will pass on the mutant gene to approximately half of its offspring. If two carriers are mated, approximately 25% of the litter will inherit a mutant gene from the dam and a mutant gene from the sire and be affected with CLAD. Being able to identify carriers will allow owners to avoid mating two carrier animals and prevent the birth of CLAD-affected puppies. Crucially, the availability of the DNA test allows carrier dogs to be used in breeding programmes, thus allowing the preservation of potentially important breeding lines. If proven carriers are only mated to genetically clear dogs,the very worse that happens is that about 50% of the litter will be carriers, the other 50% will in fact be genetically clear. Further more DNA testing the puppies in the litter will sort the offspring into carriers and clears. The clears thus identified can then be used to continue a breeding programme. If owners take full advantage of the available test, and ensure that carriers are only ever mated to clears and, crucially, only use the clear progeny to continue a mating programme, the frequency of the mutant gene will drop quickly in the population. There will then be a significant reductionin the disease burden caused by this particular condition. I think one of the main points to make is that the DNA test will allow breeders to reduce the frequency of the mutant gene without having a significant affect on the overall gene pool in the Irish Setter; important blood lines will still be able to be preserved if they have carriers in them.

Partial CLAD

There have been several examples of dogs with CLAD-like symptoms but in a milder form, leading to the question "Is this the same disease or a different one?". Partial CLAD, as it has become known, was part of the Swedish study that identified the mutant gene that causes CLAD. Dogs with partial CLAD were shown to have the same genetic mutation as those that had CLAD. There is there fore no scientific evidence for two different conditions; CLAD and partial CLAD are the same genetic disease. The fact that a small number of affected animals have milder, partial CLAD probably reflects the fact that there areother genes in the dog that can somehow modify the effects of the genetic mutation that causes CLAD. From a practical stand-point, CLAD and partial CLAD should be seen as identical conditions.

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