Genetic Testing for PLN-Associated Variant Genes at the University of Pennsylvania School of Veterinary Medicine
There are many causes of PLN for any dog. However Wheatens have shown a higher than expected incidence of the disease. This indicates a genetic predisposition for the problem. It has always been suspected that the mode of inheritance would not be straightforward. The research from the Wheaten-Wheagle colony at the University of North Carolina indicated a dominant possibility while what was being seen from the wider population supported a complex inheritance of more than one gene, with or without environmental triggers.
The Soft Coated Wheaten Terrier Club of American has an excellent website with information on this project covering the research, testing procedure and breeding impact. It also included step-by-step instructions on taking a DNA sample with a cheek brush and a very detailed question and answer document. See www.scwtca.org/health/dnatest.htm.
However, to try and simplify a long and complicated research project - a genome-wide association study (GWAS) used by the researchers located a chromosomal region that had alleles (genes) associated with PLN-affected dogs. Further study pinned this down to two adjacent genes on the chromosome which cause a change in the amino acid sequence (amino acids are protein building blocks) in the proteins they produce. This affects the two proteins (nephrin and filtrin) the genes encode which in turn affects the structure of the cell adhesion proteins in the bit of kidney called the glomerulus. The mutations in these two alleles predisposes a dog to PLN. It is not yet known if one or the other or both are responsible for PLN, or indeed, if there may be yet another gene involved.
Each dog gets 2 copies of each gene, 1 from its sire and one from its dam. So far in the study, whenever one gene has this predisposing change, the other gene also has the predisposing change, so it is easier to consider them together for discussion as 'the variant alleles'. For instance, if a dog is 'homozygous positive', it has 2 copies of the predisposing variant alleles, which means it received 1 copy from the sire and 1 from the dam. If it is 'heterozygous' it has 1 copy of the variant alleles (that it received from either its sire or its dam), and if it is 'homozygous negative' or 'clear' it has no copies of the variant alleles. Dogs with 2 copies had the highest risk for developing PLN in their lifetimes.
The various implications of your dog having both, just one or none of the mutations are covered in the SCWTCA's Question and answer document (sections 29 to 33, pages 6-7). It is not 'a definite' that, if your dog is positive for both mutations, he will definitely get PLN. It does mean that he is at higher risk. Do read the document entitled "Questions about the PLN research" in the menu to the right of their DNA research website page. If you do not have access to the Internet, the Club Secretary can provide a copy on request.
Considerations to take when breeding in regard to dogs with and without copies of the variant alleles are also discussed at the end of this Question and Answer document (pages 7 - 9).
The test is considered a direct gene test rather than a linkage test. A linkage test shows that there is a change close to the problem. The PennVet research supports the assumption that they are looking exactly on the problem, which is more accurate. Interestingly this assumption is supported by the fact that mutations in the nephrin protein in humans cause a very severe PLN.
Testing your Wheaten
Fortunately for Wheatens, Dr. Henthorn has also developed the test so that dried cheek swabs can be used for collecting DNA samples from the dogs. This means there is no trip to the vet, no dodgy ice packs to keep blood or tissue samples viable, no limited 'shelf life'. Cheek swabs can be sent by post from anywhere - no customs forms required.
For those wishing to send off DNA samples to the PennVet team for the PLN-Associated Variant genes test, our Club has free cheek swab kits available. Contact The SCWTC Health Team, c/o Mrs. J.A. Creswick, 96 Newgate Street, Morpeth, Northumberland NE61 1BU (01670-512832 or email@example.com). For each dog, the kit includes the sample submission form and two cheek brushes.
The PennVet team is still interested in having samples sent in by all owners as this will help them understand the distribution of 'clears' (dogs without either of the two predisposing genes or alleles) and 'carriers' (one or two copies of the predisposing alleles). This information gained from samples sent in from the UK should provide an indication of the prevalence of the PLN-predisposing alleles in our Wheaten population.
The SCWT Club of America's website www.scwtca.org/health/dnatest.htm has very clear instructions on how to use cheek swabs to take a DNA sample from your dog. Their DNA sample submission form also has some do's and don'ts. A submission form is with your test kit.
To receive the results of the DNA test for your dog(s) you need to send $125 for each dog to be tested. You will need to send a photocopy of your dog's Kennel Club registration form.
If you wish to simply support the research by sending a sample from your Wheaten, just write "anonymous" where it asks for your signature under Payment Information. If you then decide later that you want the results for your dog, this can be arranged after payment.
As with any research project, all results are confidential to you and the researchers. No details of any particular dog will be disclosed, unless you yourself wish to do so.
Please do your bit to facilitate the research into this inherited Wheaten problem. All it will cost you to send in a sample from your dog for research is postage.
The more samples the researchers have to work with the more information they will gain on this disease. It looks like we can, via this simple-to-do DNA test, lessen the spread of these variant genes in the next generations.