Q. I saw from your earlier e-mail that you and a geneticist had zeroed in on one dog as the possible source. I would really like to know who you think it is. After studying the pedigrees, I initially thought it was Hardacre Pied Piper, but the older pedigrees threw me. It was my understanding that both parents must be carriers for the defect to emerge in the progeny, right? In some, he was only on one side. Tungwei of Coburg seemed logical as well as Pontac Adham Tarhib. But the newest pedigrees I found on the ILAC site, have really thrown me. There were different dogs in the pedigrees this time. I have English pedigree books so I have been able to go pretty far back into most of the pedigrees and they were pretty inbred right from the start.

A. When I said that there appeared to be a "single source" uniting these 15 pedigrees, I did not mean to imply that a single dog could be identified. Rather it is a group of dogs - specifically those coming down from Pied Piper, and before him, possibly from Jigmey Tharkey of Rungit - a dog acquired in India. Two or three of these PRA pedigrees are quite old and we can only find Piper ancestors. It is quite obvious we have identified a "stream". All of the tributaries may not have been found, but we know where the main body of the stream is.

Q. I will know for sure when the rest of my dogs are tested (most were tested at a younger age already), but what has been tested and found clear recently have pedigrees linebred on Pied Piper and the others except for Hackensack and Fol-de-rol. I can see my being lucky in a litter or a couple of litters, but 15 years of line-breeding? If all my dogs end up clear (I have access to quite a few pets so I'll be able to check multiple progeny per litter and in some cases full litters), then there has to be a more complex answer to the problem. Don't you think? Or is it just simply that my first bitch wasn't a carrier and I didn't have breeding access to others that were related? However, My male, who was imported at age 6 and is a Hackensack grandson with similar ancestry to my foundation bitch from England, was bred to the first bitch's progeny, yet adults are coming up clear of PRA, and at age 12 is clear himself. I can't believe I'd be that lucky, do you?

It makes me wonder if there is an outside factor that is causing this because Joan's stuff out of Earle has all been coming up normal too, hasn't it? And they have linebred on him. Could a contaminant of some sort caused the mutation that has resulted in the PRA? I have always been under the impression that a mutation usually has some sort of catalyst. I'm not real up on genetics, but it seems strange the Saxonsprings dogs that were exported to the U.S. do not seem to be producing or have produced pups with the problem. Is it the dilution or is it something else?

A. Even blind dogs can have clear brothers and sisters. In the mating of a carrier, only one half the pups will be carriers. When you bring a foreign line into a huge gene pool like the USA, any defects are likely to be diluted out by half in the first generation, and another half in the next generation. We are not likely to see any PRA from that line since it has not been preserved pure - full strength as it were. You might find it again with intense inbreeding, that is if the imports were carriers to begin with.

The mathematical estimate, based on the sample size and the number of carrier dogs in Europe would be from 10% to 30%. 30% is the calculated estimate, but the real number may be considerably less, because of skewing of the sample. But let's say the real number is 20%. That means that 1 in 5 of the males and 1 in 5 of the females are carriers. The chances of two carriers being mated randomly is 1/5 x 1/5 or 1/25 (1 in 25). So even if the carrier rate is 20% only 1 mating in 25 would have the possibility of producing an affected dog. I do not think that there were that many Saxonsprings imports to this country. Then you factor in the dilution.... And the chances become very small indeed.

As far as a contaminant goes. There are several different forms of PRA which has been described almost 100 years ago. It afflicts almost all breeds of dogs. Even wolves have been found with PRA. The contaminant would have to have been very ancient - perhaps 15,000 years ago, when Man domesticated the first wolf and called him "dog".

As I said before - it is no single dog - it is a lineage. I think a clear case can be made for the Pied Piper group. When you go further back, it gets harder to trace. But that really is not the point. The point is that the common element in all of these pedigrees is the old English lines. But pedigrees themselves may not be completely reliable. For all we know, years ago someone's Cairn Terrier may have gotten in there and contributed some genes. I've often wondered how only the English dogs carry brindle. The Cuttings and the Baileys got their dogs from the same sources. How come the English dogs are so heavily brindle and neither the Hamilton Farms dogs, nor the Orlane's dogs ever produced brindle? There are a lot of unanswerable questions. This preoccupation with pedigrees only clouds the issue. All you can say with certainty is:

We know the English lines are :
1. inbred.
2. producing dogs with PRA

We know the American lines are:
1. less inbred
2. not producing significant numbers of dogs with PRA.

Answer: Exercise care when breeding old English lines.
1. Don't inbreed them.
2. Check English stock before using

Stop looking at pedigrees for an answer. They are only as reliable as the people who wrote them. I don't know those people, but I do know other people, and my experience with people is that they all cheat just a little. And I have no reason to believe that the British are more honest than all the other people I know.

Q. I was thinking after reading the last of your communications and an idea came to me. We are only looking at this problem from one perspective -- 15 AFFECTED dogs out of 500 clear. Why not look at the other side of the equation and study the pedigrees of the dogs that have been tested clear? If we compare the pedigrees of the dogs that are clear (only those that are CERF certified, with certification from overseas, or in the case of dogs that may have other eye problems, a written letter that the dogs are clear of PRA by a certified veterinary ophthalmologist. I would be willing to set up the database of clear dogs. I can compile this data and we can study them to see if there is a pattern or "tributary" which leads to healthy eyes. What do you think?

A. ILAC has done just that - established a registry of clear dogs. Pedigrees will not be of much use, though. With a recessive gene, the same pedigree that produces an affected animal, will produce 3 times as many clear animals. As I already said, The pedigrees are useful only in a very general way - not to establish anything specific... Trying to squeeze more out of pedigree study is useless - perhaps dangerous, because it may lead to unwarranted conclusions.

The science is only as good as its data. In the case of pedigrees - it is probably shaky at best. In general terms, yes. I know that a puppy from kennel X was the product of a particular bitch and one of Mrs. X's dogs, unless she had only one. (If she sent the bitch away - we have to rely on two people's honesty instead of one.) In general terms I am sure of the bloodlines represented in this puppy, but I will never be sure, without DNA typing, exactly who the father is. The pedigree may go back in this country 20 generations or more. That is 20 opportunities for the pedigree to be wrong. How good will the "science" based on those data be?

The same goes for affected pedigrees. In a general way we see a pattern emerging, tying all these dogs together. A few mistakes in the pedigrees would not significantly alter the pattern, so we can rely on it to a certain extent. So when we see a dog missing - particularly on the sire side, it does not change the effect of the group of pedigrees. Also it depends very much who the sire is. Imagine that some lady spent the $$$$ to breed her bitch to Mr. Wonderful, then she got her bitch home and one of her own stud dogs climbed the fence and bred the bitch. Do you believe for one minute that she would get rid of those puppies without pedigrees? Who do you think would be listed as the sire on their pedigrees?  Studying pedigrees when you have a great big batch of them has some general use, but beware of hanging too much importance on them.

Q. The reason I asked about a contaminant causing the gene mutation is that I had a friend that had a problem years ago. She bred her bitch and had developed a horrible sand flea infestation in her kennel. She sprayed the kennel with an insecticide. The bitch's pregnancy was apparently at a time when the puppies hearts were forming. All 5 puppies in the litter were born with a rare heart defect and had to be put to sleep. She was devastated as the bitch had been bred before and had normal pups. She went to Purdue and I believe they necropsied the puppies. It was finally determined after careful examination that the mutation which caused the heart defect was from the insecticide not a hereditary factor.

What if something had occurred or a product was being dispensed for flea control or disinfecting that could have created a similar defect in England only in the retina? Would the progeny that came down from this man-made mutation then carry this gene and produce it in the offspring just as it would in a true hereditary defect? The thing that bothers me with this entire situation is that the problem seems to be localized to one geographic area. You have proven that the US does not have a blazing problem, have there been any diagnosed in Australia? And if so, were they whelped and imported from one of the other countries? Or Australian born and raised?

A. The "mutation" you speak of is not a mutation, but a congenital malformation - a developmental rather than a genetic problem. This is an acquired problem. It happens when some environmental factor interferes with normal fetal development. In humans, it can be excessive alcohol, thalidomide, German measles, - we have many examples of teratogenic (monster-forming) drugs and substances. The difference is that these factors are not stored in the animal's DNA, and cannot be passed on to its children.

England is an island to which no animal can enter without a long quarantine. This status encourages the use of what is already there. The foundation stock was perilously small to begin with. Geneticists have calculated that the minimum number of "founders" of a breed to have adequate genetic diversity for a sustainable population is 6 to 20. England had 5. The USA had 8. The original supply of genes was not sufficient in England or North America. And even though both countries started out with inadequate founding populations, The North American population was unaffected by war, and did not undergo the intense recent inbreeding that was done in Britain.  (Recent inbreeding is much more deleterious than "old" inbreeding, for reasons I can't get into right now.) It is a great credit to the hardiness of the Lhasa that any population at all survived a world war and such intense inbreeding.

Scandinavia's problem originated at a time when Sweden and Norway were also quarantine countries. Limiting importation encourages inbreeding. Two Intrepid sons were imported and everyone rushed headlong to breed and then inbreed on them. It was a stroke of bad luck that their mothers were half sisters who carried an unfortunate gene..

Australia had mainly English dogs, but has also always had an input from USA and elsewhere, situated as it is on the Pacific rim. They also have not inbred as much. They also had a different group predominating - the Cheska stock and Furzyhurst stock. These went back to Licos and Mrs. Grieg's Ladkok imports. They were not the same as the Hardacre group. Even though the pied Pied Piper line went to Australia, he probably did not contribute as many progeny as in England.

Then you must consider the odds. As I have been constantly repeating, if you don't have the gene, you can't transmit it. If the gene has a low frequency, as it probably did before Intrepid came on the scene and started everyone inbreeding in order to make another little Intrepid, perhaps only one in 20 dogs carried the gene. This meant that only one litter in 400 has the POSSIBILITY of producing a PRA puppy. If we figure 4 pups to a litter, that means there had to be 1599 dogs with normal eyes for every 1 dog with PRA. Out of all those matings, the number of dogs not carrying the gene was 1448. So you see that the odds of a particular dog carrying the gene are low unless an unlucky choice for inbreeding happens to shift the odds. The present hysteria is unwarranted. All you have to do is outcross, and then not inbreed, and the problem is reduced back to it's original low level. It is really so simple.