By Fiona Douglas, B.Agr.Sc (HONS) M.S.W.
AKA Lady Fi
Quite a few years back now I wrote a couple of articles (e.g. Blindness test flawed?) concerning the dubious DNA test for PRA in miniature dachshunds and the serious implications it had for the future of the breed. Now I stand vindicated, and by the researchers themselves.
PRA stands for ‘progressive retinal atrophy’ and is a form of blindness. In certain dog breeds (dachshund included) there was frenzied concern over its supposed rising prevalence in the 2000s, and this just happened to coincide with a newly released DNA test for the disease. The frenzy was such that to this day it remains one of the most common questions I am asked as a breeder: ‘Have you tested for Cord 1 PRA?’
It was, and still is, billed as a huge thing: kennel clubs were promoting this new DNA test to their dachshund members. Hundreds and hundreds of dachshunds were screened and the dogs’ names and test results were made public on the web. A dog was recorded as ‘clear’, ‘carrier’ or ‘affected’. Imagine the great dogs who were sidelined for breeding on the basis of an ‘affected’ result? Not to mention living with the spectre of one day going blind.
My article Blindness test flawed? explains why I believed the test to be unsound and the associated dangers of screening breeding dogs on the basis of erroneous test results.
Briefly, the gaping hole I saw in the science behind this DNA test was that no one had followed up to see if the test worked in the real world. That is, the test had been not been validated in the wider dachshund population, yet despite this there was haemorrhaging of the precious breeding dog gene pool based on the results of this test. And the data to suggest the flaw was glaring: it lay in the many hundreds of published test results where false positives and negatives abounded.
I quoted figures in my article concerning the extraordinary percentage of dogs being recorded as ‘carrier’ or ‘affected’: it was over 50%. A quick calculation revealed the impossibility of this being in any way correct. Simple recessive/dominant inheritance was the model the test was founded on, so this tells us that some 25% of dachshunds should be walking around blinded from PRA. Not so. Our incidence at Dachshund Australia in more than a decade of breeding is zero.
Years after the release of the test the researchers belatedly directed their attention to this glaring anomaly. Namely, they set about exploring the poor correlation between the long haired miniature dachshunds (MLHDs) genetic test result for PRA and their actual eye health. (1)
The Cord 1 ‘PRA gene’ was tested for in 200 normal (control) MLHDs and in 510 dogs from 66 other breeds. To fine-map the Cord 1 gene location in the MLHD, 74 PRA cases and 86 controls aged 4 years or more were DNA tested within the previously mapped Cord 1 critical region.
And the results?
Substantial inaccuracies. Namely, 16% of normal, healthy eyed MLHDs tested as ‘affected’: so false-positive results. Sadly for the breed, this extrapolates to 16% of healthy MLHDs being excluded from the breeding gene pool for no reason at all and over many years.
And it didn’t stop at false-positive results. Staggeringly, the false-negatives came in even higher at 20%. That is, one in five dogs who actually had the PRA disease didn’t produce an ‘affected’ test result.
What a mess. Screening for breeding suitability based on a test whereby 16% of those excluded from breeding could be expected to be perfectly healthy, and then some 20% of dogs with the disease appearing as ‘clear’ or ‘carrier’ could be retained for breeding.
In the words of the researchers, ‘…additional as well as alternative factors may account for the substantial genotype-phenotype discordance.’ (1)
Science-speak for a stuff-up?
Marketing to extinction
Unfortunately the dodgy PRA DNA test is merely the tip of the iceberg; many more canine DNA tests require similar scientific scrutiny. I only hope this transpires before there are no purebred dogs left.
Knowing some of these DNA tests don’t work, why do we still see them promoted by the developers and breed associations alike? In my book it is nothing short of unethical: to market a product that claims to improve breed health, when in fact the real outcome is to push our purebreed dogs towards extinction.
(1) Keiko Miyadera, Kumiko Kato,Jesús Aguirre-Hernández,Tsuyoshi Tokuriki, Kyohei Morimoto, Claudia Busse, Keith Barnett, Nigel Holmes, Hiroyuki Ogawa, Nobuo Sasaki, Cathryn S. Mellersh, and David R. Sargan
Phenotypic variation and genotype-phenotype discordance in canine cone-rod dystrophy with an RPGRIP1 mutation,
Mol Vis. 2009; 15: 2287–2305.
Published online 2009 Nov 11.