Why PRA here and not there?

There has been much speculation as to why PRA has suddenly emerged as a significant problem in UK dogs and dogs derived from UK sources.  Several of the leading Veterinary Ophthalmologists I interviewed here in the USA claim to have never seen a case of PRA in apsos, or at most, one or two in their entire careers.  People in the affected countries assume that the disease is just as prevalent in the USA as in their countries, but simply has not been discovered here for lack of testing.  Who is right?  What could explain a difference in the incidence of PRA between the UK and the USA.

The most obvious answer is that  different genes  are differently distributed in isolated populations.  The reasons why this should be the case can be explained by the following  scenario using the known facts but which makes some very plausible but unprovable assumptions..

When the first dogs were imported from Asia to the US, there were 5 dogs and 3 bitches.  A few more followed in a few years, so let us say there were 10 original founders.  If none of those dogs carried the gene for PRA, the gene frequency in that population would be zero until such time that another animal carrying that gene was imported.  Apsos were bred up in numbers fairly rapidly in this country.  Within a few years of their arrival, thousands of Apsos had been bred.

Let us estimate the population at 1000 Apsos in North America at a time when the gene frequency was still zero.  Now let us now introduce an imported dog which carried the gene for PRA.  We now have one thousand clear dogs and one carrier.  At this point the gene frequency in North America is 1/1000, or 0.1%.  With continued breeding and no selection against the gene, the frequency would of necessity remain at 0.1%.  The reason for no selection is that the chances of two animals being bred together in a population frequency of 0.1% is 1/1000 x 1/1000 or 1/1,000,000.  One in a million chances of a litter being produced by two carriers of PRA!  No wonder it was never selected against.  It was never seen!

Even if there were only 100 dogs in NA by the time the gene was introduced, the chances of a litter being born of two carriers was 1/100 x 1/100 or one in 10,000.  Even then. since PRA is a simple recessive gene, only 1/4 of the pups could be affected, which brings the number of expected affected pups to 1 in 40,000.
Now consider the situation that might have obtained in another country, isolated by quarantine restrictions which discourage importations.  Let us assume that out of ten original imports, one of these carried the PRA gene.  This gives us a gene frequency of 10%.  As these dogs multiply, the gene frequency remains constant.  Why? Because there is no selection against it. (one cannot select against something that one has never seen.)  Why was it not seen? Several reasons actually. In a 10% carrier rate, the odds are 1 in 100 of a carrier to carrier mating, and 1 in 400 of seeing an affected pup.  Secondly, the onset of clinical signs and symptoms of the disease are late, and subtle.

Now. 40 years later we have two populations, one of which has a carrier rate of 1/1000 and another population with a carrier rate of 1/10.  Yes, we have a few importations back and forth, but the populations are so large at this point that these few infusions of genetic material make very little impact on the established gene frequencies.

But wait... Suddenly, a very unusual dog is imported to the Island nation.  He is bred to as many bitches as he can service, and produces some 900 puppies!  His chances of being a carrier are one in one thousand.  The bitches to whom he is mated have a one in 10 chance of carrying the gene. This means that at least one in 20 puppies born will be carriers.  The imported stud had a 1/1000 chance of being a carrier, coming as he did from a population where the gene was rare.  None of the first generation of that breeding were found to be affected, so it is very unlikely that the imported stud was a carrier.

Because this stud was so highly regarded, his children were at a premium for breeding.  Inbreeding and linebreeding (a form of inbreeding) on these children was extensively practiced.  The most successful of his children became heavily used studs in their own right - some becoming the foundation stud for almost every dog in a small country. If these most successful  children also happened to be the one in 20 carriers,  then the PRA gene would be  rapidly concentrated in the population.  (Geneticists call this the "Matador Effect".)

Predictably, to everyone's dismay, the evidence of the concentration of the PRA gene finally appeared.  When the carrier rate approached  the 30% level, 3% to 4% of the pups born were affected: a number finally great enough to no longer escape notice.  Before that there simply were too few to light up the radar screen!

Yes PRA undoubtedly exists on both sides of the Atlantic.  The difference is a 100 fold variation in incidence. (The Purdue database records tests on 10,000 Apsos over a 33 year period, with a finding of 30 cases, less than one per year per 10,000).  The only reasonable explanation of the differing incidence in the two populations is a difference in the  carrier status of the FOUNDING populations, plus an extraordinary degree of inbreeding on a few carrier matadors.

Moreover, owing to the present large population size in North America, introduction of a few dogs carrying PRA into the population will have a negligible effect on the overall prevalence of the defective gene.  In countries with smaller populations, inbreeding on native carriers, or introduction of numbers of carriers and inbreeding on them will have a much greater impact on the prevalence of the gene.