Testing of dogs: TNS

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TNS - Trapped Neutrophil Syndrome

Trapped Neutrophil Syndrome is recessively inherited syndrome affecting Border Collies.

TNS is caused by deletion of four base pairs GTTT in exon 19 of VPS13B-gene (g.4411956_4411960delGTTT, (Shearman, Wilton 2011) that results in premature stopcodon during protein synthesis. Due to this mutation the correct function of white corpuscles - neutrophils - is impaired.

Neutrophils are necessary parts of immune system of an individual. They take part in fighting bacterial infections and are important participants in acute inflammation. Neutrophils are produced by bone marrow and after maturing they are gradually released into the bloodstream.

In dog affected with TNS, the neutrophils are produced and mature correctly in bone marrow, but are not released into the bloodstream. If neutrophils are missing in the bloodstream and tissue, it is difficult for an individual to fight infections. The immune system is slowly failing. The failing of immune system can be seen in pups from as early as 2 weeks old and the pups die or are euthanized by approx. 4 months of age. The first symptoms may include apathy, loss of appetite, diarrhoea or poor mobility. Other symptoms depend on the type of infection the pup happens to contract.

The disease is inherited as a recessive trait. Dogs that have two copies of the mutant gene are affected. If two heterozygous dogs are mated, 25% of the offspring in the litter are expected to be healthy, 50 % of the offspring are expected to be carriers and 25 % of the offspring inherit the mutant allele from both parents and are expected to have TNS.

Within Border Collies breeding, inbreeding (mating together closely related individuals) was often practiced which increased the number and spreading of genetic diseases. All known dogs affected by TNS are offsprings of one common ancestor coming from Australia (Shearman, Wilton 2011). Today, there are a lot of TNS carriers among Border Collies. The frequency of mutated allele in population of Border Collie has been determined to be 0.064 in average. (Shearman,Wilton 2011). By timely detection of the carrier of this disease unwanted mating of two carriers and birth of affected pups can be avoided.

Border Collies and their TNS have been used as a model for research of Cohen syndrome in humans.

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Reference:

J. R. Shearman, A. N. Wilton: A canine model of cohen syndrome: trapped neutrophil syndrome: BMC Genomics 2011, 12:258

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Usual turnaround time: 7 business days
1 test price: 54.00 $ without VAT