banner.jpg
imagebannershadow.jpg
Trapped Neutrophil Syndrome

UPDATE 2013: TNS testing is currently being conducted by Sydney University!

TNS stands for Trapped Neutrophil Syndrome. It is an immune deficiency in Border collies. It is an inherited disorder that is very common in all populations of Border collies with more than 10% of both working and show dogs carrying the defective gene and capable of having affected puppies.

  • TNS is a condition where the bone marrow produces neutrophils but they are not released into the bloodstream. This results in an impaired immune system that cannot fight infections.
  • Symptoms are variable, many of the reported TNS puppies have been born looking normal but others have been born small.

  • Some puppies with TNS have been small and fine boned with narrow heads at some point but this may not be evident until approx 16 weeks.

  • A common first sign is a bad reaction to vaccinations with signs of fever.

  • Blood tests may show an abnormally low segmented neutrophil level but TNS can only be definitely diagnosed by bone marrow biopsy.

  • Any puppy that shows any signs of infection or failure to thrive is a possible case of TNS.

  • There is no cure for TNS and it appears to always be fatal eventually. Antibiotic and steroid treatment can help affected dogs live a relatively active life.

  • TNS is an autosomal recessive condition.

  • The symptoms are extremely variable and will depend on the bacteria that the pup encounters. There may also be other genes that effect the disease expression.

  • Some dogs do not show symptoms until later in life. Older puppies & young adult dogs diagnosed with immune system problems may have TNS so they should also be tested with the DNA test

  • There is no evidence that carriers of the TNS defect have increased immune problems.

 

DNA Testing - Current Process

Following the untimely death of Dr Alan Wilton and the re-assignment of his lab for other research purposes by the UNSW School of Biotechnology and Biomolecular Sciences (University of NSW), the university informed the BCCNSW that they could no longer store Border Collie DNA samples that had been collected for DNA research or continue the DNA testing.  Destroying these samples would have been an immeasurable loss to the Border Collie breed, as many of the donor dogs are no longer with us, and the samples are also be vital as they ensure we can establish lines of descent for future disease research.

The ANKC Canine Health and Welfare Committee came to our assistance, and approached the Faculty of Veterinary Science Department of the University of Sydney, to see if storing the samples could be part of their Canine Biobank. The faculty was very helpful, and the samples have now been moved to Sydney University.

As well as providing the storage of the DNA samples, Sydney University is now continuing research into hereditary conditions of the Border Collie and as part of the research it is now testing for TNS and CL.

If you wish to contribute DNA and have your dog tested, first you need to have a single 2-10 ml blood sample taken by an experienced veterinarian, in accordance with the lodgement form (link below). All aspects of the study, including results, will be confidential and no animal or owner details will be released.
The cost is $110, which covers the both TNS & CL testing, but at this time CL testing is still not in place at the University but will be performed on any samples lodged once the University has restarted CL testing.  Payment is to be made at the time samples are submitted and payments should be made to The Border Collie Club of NSW preferably via PAYPAL – paypal@bccnsw.com or by cheque, made payable to The Border Collie Club of NSW Inc. Please include the PAYPAL receipt or the cheque with the samples on shipment.

The Biobank Consent form (TNS & CL Testing) can be found on the BCCNSW website at http://www.bccnsw.com/dnatesting.html .

Watch for further updates as they become available.  If you have any further enquiries or questions, please contact Judy de Jong judydej@gmail.com .

 

 

DNA Testing - History

In early 2007, Jeremy Shearman in Dr Wilton’s lab, identified the genetic defect that causes TNS and developed a simple DNA test to identify carriers. The test amplifies DNA extracted from blood or mouth (buccal) swabs using the Polymerase Chain Reaction. The CL test in Border collies developed in Dr Wilton’s lab and CEA test from Optigen work in a similar way. Application of the TNS test has shown that TNS is widespread through the Border collie breed (Table 1). Proportions of TNS carriers from testing are an overestimate of the population frequency because dogs related to carriers are preferentially tested. It is estimated that 10% to 15% of Border collies worldwide are TNS carriers. In a randomly selected sample of Borders tested from Norway 14% carried the TNS mutation. Testing has confirmed the TNS mutation in UK, US, Japan, Europe and Scandinavia as well as Australia and New Zealand (Table 1).

Breeders can now test for TNS before breeding to avoid mating two carriers and risk producing affected puppies. Puppies from matings between a carrier and a TNS clear will produce (on average) half carrier pups and half clear. Puppies can be tested at a few weeks of age from a blood spot on an FTA card or a buccal swab sample (Table 2).

About 4000 Border Collies have been tested so far. The high incidence of carriers (>10%) in all lines suggests that the causative mutation goes right back to the beginning of the breed and may even be found in other collie breeds like CEA is. For this reason, it is recommended that all lineages be tested. Once the parents have been tested clear for TNS it is not necessary to test the pups, they can only inherit the genetic defect from a carrier parent. Both parents of any affected dog must be carriers. Many lines that have shown no sign of the disease may still have carriers, and this includes ISDS lines and Australian working dog lines.

Up until his untimely death in 2011, Dr Wilton’s lab where the research was done was the only lab that provided TNS testing. Dr Wilton's lab cannot give Clear by Parentage Certificates for DNA tests because we are not the holders of the registered parentage information. In many overseas countries, the breed clubs that register the dogs maintain a database of test results, include the information on registration certificates and provide Clear by Parentage certificates for puppies of registered litters where the parents have been tested. We could prove paternity with DNA testing using the International Society of Animal Genetics Paternity Testing markers but this would cost as much as testing the pups directly for disease.

Dr Wilton's lab also developed the CL test. Most of the carriers identified in his research on samples submitted for TNS testing were known as CL carriers but occasional CL cases are still appearing from backyard breeders (Table 2). It is hoped that DNA testing will also enable breeders to reduce carrier rate for TNS. However, numbers of samples being tested are dropping off with 1930 tested in 2007 but only 700 so far in 2008.

Dr Wilton was working earlier in 2011 on research focussing on Cerebellar Abiotrophy, which causes ataxia and has been a rare problem with several recent cases in Borders collies. It is likely to be due to a different gene mutation than the one identified in Australian Kelpies where it is a common problem. DNA testing for inherited diseases in dogs is an effective way to improve the breed by managing the breeding population and slowly removing the carriers for inherited diseases without reducing the gene pool or destroying lines that carry desired traits.

This information was provided Alan Wilton from the School of Biotechnology, University of NSW.

It is with much sorrow that colleagues and friends at UNSW and the Border Collie community record the death of Associate Professor Alan Wilton of the School of Biotechnology and Biomolecular Sciences.  Professor Wilton passed away on 14th October 2011, after a 20-month battle with cancer at the age of 58.

Alan was instrumental in discovering the DNA test that allows Border Collie breeders to test their breeding stock which now means we can with confidence, breed our beloved Borders without the fear of pups having CL or TNS. The peace of mind that Alan Wilton gave us can never be repaid, and now to have this great man no longer with us is one of life’s great tragedies.  Alan’s legacy will be to us, our Border Collies and the future generations of healthy and unaffected dogs that will follow, all because he cared and wanted to help us.

 

Table 1. TNS mutation testing results from 1/1/2007 to 15/9/2008 for adult Border collies by location.
           
Region
TNS Clear
TNS Carrier
TNS Affected
Proportion Carriers*
 
Australia
355
70
1
16.7%
 
NZ
36
4
1
12.2%
 
UK
616
156
1
20.3%
 
USA
205
89
0
30.3%
 
Japan
39
9
0
18.8%
 
Europe
679
169
3
20.2%
 
Scandinavia
159
34
1
18.0%
 
           
Total
2089
531
7
20.2%
 
 
Table 2. CL mutation testing results from 1/1/2007 to 15/9/2008 for adult Border collies samples collected for TNS and/or CL testing
           
Region
CL Clear
Cl Carrier
CL Affected
Proportion Carriers
 
Australia
322
17
2
5.6%
 
Rest of World
1677
5
0
0.3%
 
           
 
Table 3. TNS mutation testing results from 1/1/2007 to 15/9/2008 for pups less than 110 days old when tested
 
Region
TNS Clear
TNS Carrier
TNS Affected
Proportion Carriers
All
208
168
4
45.3%

 

Return to Top