A BREAKTHROUGH

In last week's report I reviewed the progress, generation by generation, of transferring the bob-tail gene from a Pembroke Welsh Corgi into the Boxer and presented evidence that there are no health risks associated with the gene when in the single dose. But, for the double-dose, homozygous bob-tail dogs, the evidence was contradictory. Norwegian Corgi data indicated a shortage of bob-tail pups (66%) relative to the 75% expected from bob-tail x bob-tail matings, suggesting that the homozygotes are lost before birth. But there was no evidence of a reduced litter size. To search for the homozygous bob-tail would require a massive breeding programme. But, scientific advances derived from molecular genetic studies on the bob-tail Boxers and Corgis have more quickly provided the answer.

With the development of the new molecular expertise in the world of genetics and the increasing interests in studying species other than mouse and man, my crossbreeding studies in the dog had begun to attract attention outside the world of dogs. In this connection I was delighted when a human genetics group whose main interest lies in the genetics of facial features contacted me. They were looking for an animal model to test out candidate genes for human facial characteristics they had isolated. My cross between the Corgi and Boxer with their different head types seemed to provide the ideal test material. And the whole concept became a practical proposition when they learned that I had already collected blood samples over the generations of crosses and that Jeff Sampson at The Kennel Club and Matthew Binns at The Animal Health Trust had made the DNA that would be needed. All was set to go when there was a further stroke of luck.

The human genetics group had also been working upon a DNA sequence that is homologous (corresponds) with that of a mouse gene that causes a dominantly-inherited short tail. As a side project, therefore, the group asked if would I be interested in their checking to see if this gene was responsible for the Corgi bob-tail? Would I indeed? There are many short-tail genes in the mouse, so the chances that the group might be working upon the same gene was small. But, nevertheless, it seemed worth testing, and the study started. Amazingly, it was the same gene.

To show this the group sequenced (read the genetic code) all the way through the bob-tail gene of the Corgi that was used in original Boxer cross and they identified a single change in the DNA. Was this responsible for the bob-tail effect? To establish this it was necessary to show that all the bob-tail dogs in the Boxer crosses had this variant DNA sequence and all the normal tailed dogs did not. And this was indeed found (with one exception which I will deal with later). The bob-tail mutation had therefore been identified.

The findings are of considerable scientific interest, so much so that a paper has already been submitted to a leading genetics journal for publication. But, for me, the results were of more immediate practical use. The identification of the gene meant that it would now be possible to distinguish dogs having one and two doses of the gene - just by analysis of blood samples. None of the laborious and expensive test-mating would be needed.

A call went out to the Corgi people in Norway who were intercrossing bob-tail dogs. Blood samples from 13 bob-tails produced from such matings were obtained and I was able to raise one more in this country. The DNA was prepared from each blood sample and analyzed independently by the human genetics group here and by the Norwegian Kennel Club geneticist, Frode Lingaas. All 14 bob-tailed dogs derived from the intercrosses were found to carry only a single dose of the bob-tail gene. The failure to find any homozygotes among 14 bob-tails tested means that the homozygous, double-dose class must be missing. But this class must be generated at conception (Fig 12 of Part 5). So where have they gone? It can only be concluded that such pups die. But when? From Olav Hedne's ample Corgi breeding records it is clear that there is no increased incidence of puppy deaths in bob-tail x bob-tail litters after birth. The loss of the homozygotes must therefore occur before birth.

Prenatal loss of the homozygous bob-tail pups means that they die either early, during embryonic development, or later, in foetal stages. Two reasons suggest that the loss occurs early. First, no aborted or dead pups have been detected at birth. Second, based on substantial Norwegian and Swedish records, the litter size of bob-tail x bob-tail litters is not reduced as it would if foetuses died and were being resorbed. With early loss, however, an explanation for the seemingly contradictory evidence can be offered.

In animals that have a number of offspring at once (in litters) there is a natural wastage as has been well-documented with laboratory mice. Not every fertilised egg implants in the uterus. Not every implanted embryo survives to term. And, this is especially evident with larger litters when there is competition for uterine space and nutrients. Embryonic loss is common around the time of implantation in the mouse. The hypothesis for the bob-tails is therefore simply that homozygous bob-tail loss replaces natural loss. Their loss in effect enhances the chances of other embryos surviving.

Whatever the correct interpretation of the discordant evidence, the molecular data establish that the homozygous Corgi bob-tail is a lethal condition. The term, lethal, has an ominous ring to it. It suggests something totally undesirable. Yet, having pondered the issue at length I have to conclude that while the evidence of lethality is disappointing, it is not an ethical problem. Without any detectable ill-effects, the only undesirable feature of the bob-tail condition is that it will not breed true. There will always be a 25% expectation of long tailed pups appearing (see Fig 12 of Part 5). That we now know why this occurs simply means that, in a sense, we now know too much.

So! If there are no ill effects, if litter sizes are not reduced, if the only unwanted feature is the persistent appearance of some long tailed pups in litters, is this acceptable in the event of a docking ban? I suggest that it is now up to individuals to decide on this, and as I am now content that there is nothing nasty about the gene, I see no ethical reason for continuing to keep total control over these bob-tail Boxers. The situation is no different from that for all other breeds having this bob-tailed gene.

There has been relatively little enthusiasm for the bob-tails among UK Boxer breeders. But there has been considerable interest abroad, in particular, from Norway where a docking ban has been in place for some 10 years. Norwegian interest has attractions for me as the Norwegian Kennel Club already has an interest in the gene. Moreover, together with the Boxer club, they have a rigorous health policy in which all breeding stock has to pass heart, HD, and spondylosis tests and there appears to be general interest in record keeping. Sending bob-tail Boxer stock to Norway, specifically to such health enthusiasts would take a lot of the weight of continued monitoring from me and could be done as part of normal breeding practice.

Accordingly, Steynmere Hot Shot (Fig 7 of Part 5) has gone to Norway. His heart murmur-free status attained in the UK has been confirmed, and he has also been found spondylosis and HD free. His new owners (although he is actually co-owned with me) are delighted with him as a Boxer and even plan to show him. In Norway he will not be the only solid dog in the show ring, and he will be among other big Continental type dogs. He has already mated his first bitch and there are plans to mate him to a number of others. And all the progeny will be rigorously monitored. Beyond this, the dog has gone to an enviable home as he will live as a single dog in a long-time Boxer-loving family with runs in the forest each day.

There have been enquiries for bob-tail Boxers from a number of European countries and even from the States. But everyone wants bitches and I don't exactly have many to spare. At present, I only have the two bob-tail bitches (on terms) and one other puppy, plus the Hot Shot son, Total Eclipse (Fig 8 of Part 5), who could no doubt be of use were there interest. From this I think it should be clear that I cannot do much more alone.

GENERAL CONCLUSIONS

This project has effectively demonstrated that a gene can be transferred from one breed to another with relative ease. Breed type can be quickly regained by backcrossing and, after five or more generations, the chances of any "foreign" genes remaining to reverse this are very small.

The gene used had a dominant inheritance which made the transfer very simple. With a slightly different strategy, a recessive gene could be so transferred.

The Corgi bob-tail gene was selected for this project in view of its possible use in the event of a docking ban. It effectively gives a docked tail image but has the disadvantage that it will not breed true. There may therefore be other, better genes such as the short, kinked tail of the Boston Terrier or even the seemingly natural shortish tails of certain other terrier breeds. But the inheritances of these are not known as far as I am aware.

The success of the project highlights opportunity for all breeds - whenever a gene is needed for whatever reasons. Breed crosses can have an important use, particularly with health issues in numerically small breeds as The Kennel Club has already recognised. Perhaps acceptance of cross-breeding for specific purposes may be the greatest legacy of this bob-tail project.

I mentioned earlier that one presumed bob-tail dog in the Boxer backcrosses was found not to have the bob-tail mutation.

The screw tailed bitch is from the fourth generation of crossing and looks typical Boxer.