There are two types of DNA tests - causal DNA tests and risk marker DNA tests.
Causal DNA tests interrogate a DNA position that is known to cause a disease. Most of these DNA tests are for simple recessive diseases, where one gene is faulty. One is either "normal" (does not carry a variant allele), a "carrier" (has one copy of a variant allele), or "affected" (has two copies of a variant allele). "Affected" means that almost certainly the disease will occur. This is how people often (incorrectly) think of all DNA tests.
For Norwich, the PLL (primary lens luxation) DNA test and INPP5E (cystic renal dysplasia) DNA test are the two currently known causal DNA health tests. Other causal DNA tests used by breeders are the coat length DNA test (fluffy test) and the Agouti color DNA test (at is the recessive variant that causes a Norwich to be a black-and-tan).
A risk marker DNA test, on the other hand, interrogates a DNA position that has been shown to be correlated with a disease. Remember - correlation does not mean causation! So two markers do not mean that disease will definitely happen. Rather two markers means that there is a higher risk of disease. So it is better to think that two markers means higher risk than one marker, and one marker means higher risk than zero makers. One way of thinking of a risk marker DNA test is that it often tells the truth ... but sometimes lies. (Most biological tests are like this. We are just not used to thinking of DNA tests in the same way.)
All of the other DNA health tests currently known for Norwich: UAS (upper airways syndrome), DM (degenerative myelopathy), ALT (low normal ALT values), and D-Locus (color induced hair loss) are risk marker DNA tests.
If you want to see how well (or how poorly, depending on your point of view) the UAS DNA test does, look at figure 6A in the research paper from which the UAS DNA test was developed: "An ADAMTS3 missense variant is associated with Norwich Terrier upper airway syndrome". The paper is available on the web. The figure plots disease score against having zero markers (GG), one marker (AG), or two markers (AA).
The other thing to keep in mind is that UAS is not a binary disease: one does not either have UAS or not have UAS. Rather UAS exists in a range - one can have a mild form of UAS, a moderate form of UAS, or a severe form of UAS. UAS is an example of a polygenetic disease - many genes are involved in making an airway. (Another example of a polygenetic disease is hip dysplasia.) So interrogating one DNA position in one gene is not going to tell us the whole story. This explains why the UAS DNA test may sometimes "lie".
Just as in hip dysplasia where you can breed together two dogs with good hips and sometimes get a puppy with poor hips, the same thing can happen with UAS. Such an occurrance is just a bad throw of the genetic dice. As breeders we want to stack the genetic dice as much as possible in our favor. This is why breeders try to avoid doubling up in pedigrees with dogs who have a particular health problem.
My recommendation as to how to use the UAS DNA test in breeding decisions is the following. Gather your short list of possible breeding partners as you normally would without regard to their UAS DNA results. Once you have a short list, then look at their UAS DNA results. Try to choose a breeding partner that has fewer risk markers. If that is not possible, choose a breeding partner with the same number of risk markers. If a potential breeding partner is outstanding (by whatever criteria you use) over all your other candidates ... but has more risk markers, go ahead and breed to that dog. Remember, a risk marker DNA test sometimes lies.
19 Apr 2020