Trapped Neutrophil Syndrome (TNS)
Inheritance: Autosomal recessive
Symptoms: Can be variable and depend on the specific infection involved. These may include failure to thrive, poor growth, weight loss, lethargy, diarrhea and vomiting. Affected dogs may also present with active respiratory, skin, eye or ear infections and often have painful legs. Affected puppies may be smaller and fine boned with a narrow, elongated, ferret-type head.
Description:
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. A common first sign that a pup may be affected is a bad reaction to vaccinations with signs of fever. Any puppy that shows any signs of infection or failure to thrive is a possible case of TNS.
Blood tests may show an abnormally low segmented neutrophil level but TNS can only be definitely clinically diagnosed by bone marrow biopsy.
There is no cure for TNS and pups often succumb to an infection by around 4-6 months of age.
The mutation is widespread across working and show lines around the world with a carrier rate of around 10-15%. The DNA test became available in 2007.
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.