CLAD in the Irish Setter by - Dr Jeff Sampson BSc.,DPhil    


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 high doses of antibiotics. This is a 
devastating inherited condition that leads to fatal immunodeficiency.


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 man and 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 gene and be clinically clear,


* CARRIER dogs will have one mutant gene and one normal gene and beclinically 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, available from Mrs Penny Rothoff-Rook 
(01638 751000 ex 1231). The form requires the name and KC Registration number of the dog, 
its microchip or tattoo number (if applicable) and a signed 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; test results of individual dogs will also be published in the Breed Record Supplement. 
It is intended that this regularly updated database 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. Furthermore 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 reduction
in 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.