Trapped Neutrophil Syndrome (TNS) is an immune problem in Border Collies. Symptoms can be variable which has made it difficult to recognise as a genetic problem. A common symptom is recurrent infections in young pups, but some develop abnormal faces a few weeks after birth while others appear normal until vaccination when they have a bad reaction and never recover, while others live to several years of age with only occasional problems. Many cases of 'fading puppy syndrome' have turned out to be unrecognised cases of TNS. TNS is a genetic disease with recessive inheritance (like CL) which means that to have an affected puppy, both parents must be carriers (i.e. one defective and one normal copy of the gene but showing no adverse effects) and about one quarter of such litters will be affected.
Dr Alan Wilton and Jeremy Shearman at the University of New South Wales in Sydney have identified the gene that is defective in TNS through study of Australian affected litters. They can trace the path of this TNS mutated gene through the pedigrees and predict TNS carriers. They have not had access to the English TNS cases reported recently but are keen to see if it is the same problem and if they can detect the defect in English lines with current technology. TNS has also been reported in Working Border Collies in Australia so the mutated TNS gene may have been around in the breed for a very long time and all TNS cases have a common cause and origin.
The current TNS research is to identify the actual DNA change that causes the defect in the TNS gene. This would allow testing of any dog for carrier status of TNS without any information about its pedigree. Information from DNA testing can then be used by breeders to gradually eliminate this disease from the breed.
1) How accurate is your current test percentage wise?
The current test is more than 99% accurate for identifying carriers in samples closely related to known carriers from the Australian lines with TNS. We are just following the DNA with the mutation through the pedigree. If there are large gaps in the genotyping of animals in the pedigree between the known carriers and the tested animals it becomes more difficult to do that and leaves room for possibility of misinterpretation. Though everything is checked human error is always a possible source of error.
If, in the unlikely event, there are other sources of TNS mutations the current test may not recognise them. For example, I cannot tell whether the current test is applicable to the cases of TNS in the purely English lines until I get enough samples of animals related to those cases and do further research.
2) How much more accurate will the DNA test you are trying to define percentage wise?
The DNA test we are developing will be 100% accurate as it will look directly at the cause of the problem. It will be applicable to any Border Collie regardless of its pedigree and needs not be closely related to known carriers. Whether the cause of TNS in the pure English lines is the same as in the Australian lines is yet to be determined and it will be part of the continuing research to develop a test for all types of TNS.
3) Will those dogs that have been already tested under the existing test have to be re tested to guarantee if they are clear, a carrier or affected?
When the new test is available, as part of our quality control program we will retest a large sample of carriers and clears as defined by the current test to ensure there are no discrepancies. If, in the remote chance there are, the information will be widely publicised, and the samples in hand tested as part of the research to provide as much information to the breeders as possible as to possible lines affected.
4) Is the mutation, single recessive or multiple recessive?
The mutation in the Australian lines is a simple single recessive allele with all cases arising from a common ancestor. Only when we develop the test will we be able to determine whether TNS in the English lines is caused by the same mutation in the same gene, a different mutation in the same gene, or a mutation in a different gene.
There is now quite a lot of concern with in the breed and could potentially stop people using dogs and bitches for breeding which are not actually going to create a risk to the breed.
Since we have a reliable test for TNS from the Australian lines now, my advice as a geneticist is that known carriers can still be bred from if they are mated to TNS clear animals. The pups can then be tested at a few weeks to determine which are clear and can be used for breeding future generations, and which should be used only as pets. This breeding strategy allows elimination of the disease from the breed without reducing the available breeding population as a reduction could lead to new genetic problems arising.
I hope this helps explain the current situation.
Update April 2007
Progress: Have set up a scholarship for Jeremy Shearman and much of the funds from PBHF are going to that. He is working his way through the very large gene looking for the mutation.
We have determined that we can detect TNS carriers in purely English lines. Gail Fan's Rispinge had a TNS litter and has an identical TNS chromosome to the Aust/NZ lines and Aust Working Dog lines with TNS. (The sire of the litter was from Aust/NZ lines). We have started detecting the TNS chromosome in ISDS and European lines which do not have any Aust/NZ ancestry.
Alan Wilton
School of Biotechnology and Biomolecular Sciences
University of New South Wales
NSW 2052
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