CLAD in the Irish Setter.
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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
clinically in the United States, is related to the same disease in humans (LAD) and cattle
Affected pups die early in life from multiple infections, usually recurrent infections of
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
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
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
They have now used this newly-acquired information to develop a DNA test for the mutant
a test that is being currently offered at the Animal Health Trust.
The test is able to distinguish the mutant gene from its normal
* CLEAR dogs will have two copies of the normal gene and be clinically
* CARRIER dogs will have one mutant gene and one normal gene and be
* AFFECTED dogs will have
two copies of the mutant gene and be
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
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
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
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
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,
25% of the litter will inherit a mutant gene from the dam and a mutant gene from the sire
be affected with CLAD. Being able to identify carriers will allow owners to avoid mating
carrier animals and prevent the birth of CLAD-affected puppies. Crucially, the
the DNA test allows carrier dogs to be used in breeding programmes, thus allowing the
of potentially important breeding lines. If proven carriers are only mated to genetically
the very worse that happens is that about 50% of the litter will be carriers, the other
in fact be genetically clear. Furthermore DNA testing the puppies in the litter will sort
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
of the mutant gene will drop quickly in the population. There will then be a significant
in the disease burden caused by this particular condition. I think one of the main points
is that the DNA test will allow breeders to reduce the frequency of the mutant gene
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.
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.
with partial CLAD were shown to have the same genetic mutation as those that had CLAD.
There is therefore no scientific evidence for two different conditions; CLAD and
are the same genetic disease. The fact that a small number of affected animals have
partial CLAD probably reflects the fact that there are other genes in the dog that can
modify the effects of the genetic mutation that causes CLAD. From a practical
CLAD and partial CLAD should be seen as identical conditions.
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