Understanding PLN Testing – Annual Health Testing vs DNA Testing
Wheaten people are sometimes confused about DNA testing and annual testing…when to test, which test to do and whether it’s even needed. Here’s a quick explainer.
PLN In Brief
PLN (protein-losing nephropathy) refers to damage of kidney structures that results in the animal’s body not retaining the necessary protein to sustain itself. PLN can have several causes. In Wheatens there is a hereditary cause; it is believed that variant genes impact the formation of the glomeruli. However, any dog can develop PLN from other causes. Genetic PLN in Wheatens is due to a podocytopathy which progresses to focal segmental glomerulosclerosis (FSGS), a form of glomerular disease. It may eventually lead to chronic renal failure, but it is NOT due to juvenile renal disease, aka Renal Dysplasia (RD); infections; toxicity; or many other causes of acquired kidney disease. Wheatens may also be at risk for another cause of PLN, e.g., immune-complex glomerulonephritis (ICGN), in which immune-complexes are deposited in glomeruli, secondary to immunologic stimulation due to chronic infections, neoplasia, or inflammatory conditions, such as inflammatory bowel disease (IBD), allergies, atopy, skin and/or ear disease, or a number of immune-mediated diseases.
DNA Testing
Since the incidence of PLN in Wheatens increased in the late 1980s, breeders and owners hoped to determine the genetic basis. In 2012, researchers discovered variant genes (alleles) that are associated with an increased risk of developing PLN. DNA samples from cheek swabs, blood samples, or semen can be analyzed to determine if a Wheaten carries 0, 1 or 2 copies of these variant genes.
There are actually 2 genes involved here, NPHS1 and KIRREL2, and that’s another cause for people to get confused. We can talk about them as a single package though because the genes are right next to each other on the same chromosome and so they are rarely separated by recombination. We have not found on the same chromosome that one gene is variant and the other gene is normal, in other words, the 2 genes NPHS1/KIRREL2 are found to be either both normal or both variant on the same chromosome. Because each parent gives the puppy one copy of its chromosomes for each gene (remember meiosis?), the puppy may get 0 variant genes, or it may get 1 copy (from one parent), or it may get 2 copies because each parent gave it a copy.To confuse you more, the standard lingo that geneticists use to describe the findings for testing an allele would tag a dog as ‘1-1’ if it is homozygous, ‘1-2’ if it is heterozygous, and ‘2-2’ if it is homozygous positive for the allele(s) in question. When geneticists use ‘0’ it means that the genetic test was not done on that animal and that its genotype is unknown.
It’s important to understand that the DNA test for the PLN-associated variant alleles tells you your dog’s relative risk of developing PLN during its lifetime. It does NOT tell you a dog has PLN currently or that it will definitely develop PLN in the future. Dogs carrying 2 copies of the variant alleles (sometimes referred to as “markers”; these dogs are “homozygous positive”) are at the highest risk, while dogs carrying no copies of the variant alleles (“homozygous negative”) are at the lowest risk. Dogs with 1 copy of the variant alleles (“heterozygous”) are at intermediate risk for developing PLN. This doesn’t mean “2s” will always develop PLN nor does it mean “0s” will never develop it. Think of it like the BRCA1 and 2 variants in women; inheriting one or both increases a woman’s chance of developing breast cancer but it is not a diagnosis.
Under the SCWTCA Code of Ethics, breeders must do this DNA testing before breeding. They can then use it as one tool in their breeding decisions. It is strongly recommended owners also do DNA testing as it may help your veterinarian in reaching a diagnosis if your dog becomes ill as well as tell you how frequently you should do blood and urine testing.
Annual Testing
Every Wheaten should have annual blood chemistry testing and a full urinalysis, with the addition of a urine protein-creatinine ratio test (UPC) and/or a microalbuminuria test (MA). The protocol can be found here. Annual testing is a snapshot in time of the health of your dog, revealing possible concerns that may not be apparent in his daily life. The results do NOT predict whether or not your dog will get PLN. But by doing annual testing, you and your vet can see if there are changes occurring that may require attention. Also, it is prudent to find early changes on blood tests, even before clinical signs occur, which may warn of problems Wheatens are predisposed to, e.g., renal – PLN, RD; gastrointestinal (PLE, IBD); and adrenal gland problems (typical and atypical Addison’s disease), when early interventions may be most helpful.
Annual test results are used to diagnose PLN. We have learned that treatment early in the course of PLN can result in an improved quality of life. This is why it is important to do both blood and urine testing at the same time on a regular basis.
Under the SCWTCA Code of Ethics, breeders must do this blood and urine testing before each breeding. They can then use it as one tool in their breeding decisions. It is strongly recommended owners do annual testing for the health of their dog.
How This Fits Together
Neither DNA testing nor Annual Health Testing is the sole answer to PLN. Both are necessary.
Think of it this way: DNA testing reveals your dog’s risk of developing PLN from genetic causes. Annual testing tells you if they are still healthy. Remember the BRCA example? Doing the genetic testing tells a woman if she has the damaged genes and is at risk; mammograms, ultrasounds, and MRIs identify if tumors have developed. Your dog’s DNA results will suggest the frequency of annual testing. Since dogs with 2 copies of the variant genes are at a higher risk of developing PLN, testing should take place more frequently than annually.
If you have questions, contact health@scwtca.org. The SCWTCA Health Committee under SCWTCA, Inc. and/or the SCWTCA Endowment, Inc. will find the answers to your questions.
