Kerry Fowler was to give an address on the genetics of PKD; to be followed by a joint address by Drs. McCowan and Lavelle on the disease process, diagnosing it and reaction to it.

2. The Genetics of PKD - Kerry Fowler

Gregor Mendel, considered as the father of genetics, worked with peas and noted that they were not all the same; being green or yellow and smooth or wrinkled. He puzzled over why they varied and about the theory of inheritance. He decided that inheritance was not decided just by what could be seen.

We are now able to build on this theory of dominance and recessivity, asking why some cats just develop the odd cyst, yet others have massive cysts and die from them. Dr. Biller and colleagues published their ideas in 1996. The problem is more widespread than we originally anticipated. We now know that 2 - 3,000 cats are affected world-wide.

Unfortunately, the gene responsible for PKD in cats is not known yet. New genetic concepts have been used to diagnose and manage PKD in human families. Further, if the gene can be isolated in people, it is likely that the same gene will be responsible for PKD in cats because we share very similar genetic make-up from the one common mammalian ancestor about 135 million years ago. After the apes, cats are the most genetically similar to humans. People have 46 chromosomes, cats 38 and mice 40, though on approximately 80,000 genes reside on these chromosomes.

In addition, some genes are in a similar order on the chromosomes of cats, people and mice, which makes it possible to work out where the PKD gene might be in the cat, as it is already known in people.

It is not just the physical appearance of the cat which we is made up of gene products. There are hundreds of muscles, cartilage making up the body. It has been estimated that about 7,000 genes are required to form the liver and similarly thousands of genes are involved in kidney formation. Microscopic examination of an incredibly thin slice of the kidney shows us both its structure and function. Its genetic blueprint, the chromosomes, can be seen by large magnification of part of the kidney cell. In this way, the chromosomes can be paired off by photographing them and comparing them with other chromosomes. These autosomal (non-sex chromosomes) are all pairable according to size and shape.

A study of chromosomes can then be taken one step further. In the 1950's, it was worked out that they are made up of DNA (deoxyribonucleic acid), which is a ribbon-like structure. The code for determining the DNA is very simple, as they are all one of either A,C,G or T letter type. The trouble is there are billions of DNA letters. Nonetheless, in the next five years, it is estimated that scientists will have decoded the sequence of letters that make up all the human genes.

Mutations are an interesting variation of DNA structure, as they may occur if one piece is missing in the DNA, and they can occur if there is a virus present or from exposure to ultra-violet light or chemicals. Not all mutations which result are detrimental to health, but PKD is one genetic mutation that is.

To decode the letters that make up the DNA, scientists make up a gel with DNA, expose it to an electric charge, which causes the ACGT letters of the DNA code to separate out. This separation can show us if the DNA has been misspelt i.e. a mutation has occurred.

Despite finding the same mutation in a number of family members, there was a great variation in the severity of presentation. There was a case in identical twins where only one of the twins developed PKD by the age of five years. The other twin was normal. ( 1 in 1,000 people have it and half of them will be terminal by the age of 50 years). When every cell inherits 1 dominant gene and 1 other gene, the question is why does PKD show up poorly in some people?

Scientists have proposed a two-hit model that may explain this. It is thought that the 1st hit is inherited, but that the 2nd. hit is acquired/misspelt during life. This may help explain why some cats go through life with little PKD effects; others develop it very badly and very early and die from it. Why this happens is still not known.

Dr. Lyons in the USA has received a grant from the Winn Foundation, to try to identify the rogue gene in cats. The Winn Foundation found that, when breeders were surveyed, they said that in the 1990's FIP was their main concern, followed by inherited diseases. However, this might be different now.

Regarding PKD, Persians have been used in many breeds, so it is not just a Persian problem. Predictive screening tests are now possible, but this peeping into the future has caused a whole spectrum of emotional responses in owners and breeders. At the Murdoch Institute, 22,000 families in Victoria and Tasmania have been counselled re human genetic problems. Murdoch has suggested a list of strategies to veterinarians to help people come to terms with genetic problem in livestock and publications are available to help us also.>br>

QUESTIONS:

Many questions and comments from the floor were added. The main points of clarification are summarised below.

Cats which inherit a dominant "X" PKD gene from both parent are genetically "XX" for PKD. Other affected cats can be "Xx". Some average likely outcomes of breeding with these two types of cats show that -
a mating of "XX" and "Xx" parents produces kittens all with PKD.
a mating of "Xx" and "Xx" parents produces 25% kittens negative for PKD.
The issue still remains as to why some kittens still die very young.

The question of what happens to monocystic cats (cyst on only one kidney) cannot be answered until the PKD gene is isolated.

A simple blood or saliva test may not be far away and testing for PKD and subsequent diagnosing will be possible at a younger age.

Dr. Lavelle commented that kittens from 2 negative parents should be negative, but breeders might like to test anyway for peace of mind, as there is a 2-5% chance of false negative results on ultrasound at this stage.

Whether genetic change in kidney cells of cats is caused by exposure to ultra-violet light is not known yet, though genetic change due to ultra-violet light is known to cause melanoma on skin surface.

Scanning at Werribee has been mostly of Persians. British Shorthairs have not been scanned as yet, though the odd non-Persian has been done. In the USA, a large number of breeds is currently being scanned. The result is not known yet, but it is likely that positive results will not be equal in all breeds.

The question of how breeders deal with PKD is difficult. There can be a range of personal options - desexing, euthanasing, breeding for negative offspring, breeding only with negative cats. How to dispose of kittens is now an ethical problem once breeders have had their cats scanned, as the selling of known positive kittens is potentially open to litigation also.

3. DISEASE PROCESS - DR. CHRISTINA MCCOWAN

Blood is filtered in the kidney, but PKD-affected kidneys have tubules which don't work properly. Pockets develop and grow larger with the age of the cat, though the number of pockets doesn't increase.

Most cats which have the disease are healthy. In fact, cats are usually 3 years old when clinical disease is seen, though this might be because of two bad "X" genes rather than only one.

As the disease progresses, tissue ceases to function and renal failure begins. It should be remembered that many things cause renal failure, so it may not be because of PKD.

4. DIAGNOSING PKD - DR. ROGER LAVELLE

It is only one year since the first screening for PKD was done in the USA. At that stage, 35-40% of cats tested were PKD positive. It is a simple question of the genetic cause - an autosomal dominant gene is operating, so it is easier to monitor PKD than it is many other conditions. It is also relatively easy to diagnose the condition with good ultrasound equipment and there are only a very few false negative results.

Most cats seem not to be affected by PKD in terms of health.

The current assumption is that most severely-affected cats are "XX" and such cats probably don't reach breeding stage.

The ultra-sound is done on both kidneys, side to side and front to back. On the scan, most of the medulla is black, but this area is not cysts. Cysts are much blacker and round the outside of the medulla mostly, though they can be inside the kidney as well as on the surface. Positive cats have "black holes" in both kidneys, as the cysts are full of liquid and the sound goes straight through the cyst rather than being reflected. One cyst could be missed in one kidney if it is very small.

In the same way, the bladder looks black when it had liquid in it.

The scanning needs to be done with a 7.5 mHz transducor. A 10 mHz machine could be used, but it would not necessarily give a better result at the moment. Kittens can be scanned at 3-4 months up to 8-10 months for the first scan.

If breeders have a positive adult cat, it is probably "Xx".

WHAT TO DO AS BREEDERS: C. McCOWAN and R. LAVELLE

C.McCOWAN

Breeders need to look at the situation in the cattery. What they do depends on whether the cat is sick or not.

It is possible to do nothing, but the cat will become worse. Cats need to be treated if they have clinical signs.
Renal transplant can be done, but only in Queensland in Australia.
Palliative care.
Sometimes PKD positive cats have problems in other organs, as well as in the kidneys. This may be because of the PKD problem.

DR.LAVELLE A number of questions were put to Dr. Lavelle during his address and his answers to these are included as part of the content of his address.

If the cat is positive and for breeding, the potential buyer needs to be informed of the problem.
Desexing all positive cats is another option. Unlike the dog world, desexed cats are allowed to compete on the show bench
If the cat/line is not valuable for breeding, desexing may be better. If the cat is valuable, breeding positive to negative may be considered, though "Xx" to another "Xx" or "xx" may be better, so that some "xx" can result.

Breeding "xx" to "xx" should be safe, though,as mentioned earlier, there is a 2-5% chance of misreading scans.

Breeders might want to keep testing for a while, though results at 16 weeks do not seem to be all that different from those taken at 10-12 months. Once a cat is about 14-18 mths, it is likely that it will remain permanently negative from then on.

A cat which scans positive when young on only one kidney and scans the same in another 12 months will probably remain in this state.

There is a chance that a very small cyst could be missed early on and show up later.

PKD cysts will most likely grow with the increasing age of the cat, so if a cat has a cyst which does not grow, the cyst may be a non-PKD one.

Tests do not show if a cyst is hereditary or acquired.

Breeders need to recognise that if they breed with positive cats, they are also taking on the responsibility of informing potential breeders/owners.

A kidney transplant would not stop a cat from being positive. It would just give the cat a better life and it would still have to be treated as a positive cat.

More than 50% kidney damage is usually the stage at which clinical problems emerge. It should be remembered that a cat can live on with one normal kidney.

There is no known connection between PKD and ovarian cysts.

Testing has only been going this year and has so far been confined mostly to Persians. The odd reports of small numbers of positive cats in other breeds may be because they have yet to be tested, because PKD is not hereditary for them, etc.

The question of sex-bias was raised, as some breeders reported positive testing results being much higher in either males; another in females. While it is still not clear because of the small number of cats tested in Victoria, the speakers felt that there should be a balance of positive cats in both sexes.

Scanning can be done without a referral from a local veterinarian unless a cat has been treated for a prior problem.

Scanning can only be done by a few people at the moment and the right equipment and ultra-sound training is needed to interpret the scans.

KERRY FOWLER JOINED THE QUESTION PANEL AT THIS STAGE.

Persians are certainly the centre of attention with PKD. It is possible that the PKD gene may be close to or linked to one of the Persian-specific genes. Furthermore, some money was donated in the USA by a breeder particularly keen to work toward identifying the

precise gene responsible for PKD and developing a blood test for early detection. The concentration on Persians may be a result of that.

PKD is one of the most common genetics diseases in people, so funding there could benefit cats.

American imports seems to have compounded the PKD problem,especially as breeders were not aware of PKD when they imported the animals.

The death rate from PKD is much lower than the 30-40% incidence of it in cats.

Other problems are likely to occur if breeders breed only from negative cats, as problems not previously known about could become more concentrated in pedigrees. It was suggested this could partly happen because our pedigreed cats are generally quite closely related anyway. Furthermore, our gene pool is shrinking also, which could make more of a problem for breeders.

All PKD positive cats are positive, regardless of how many or how large the cysts are. They all need to be treated as positive cats.

Nothing has been done yet with results at Werribee to show if particular colours or patterns are more likely to have PKD, as there have not been enough cats scanned yet to determine such trends.

There is no evidence that dry food has had an effect on PKD.

It was also suggested that cat breeders need to unite and use their power in the billion dollar a year industry of pet food. Pet owners generally also might contribute to this area of concern.

If breeders supplied data on results from breeding positive and negative cats together would help research at Werribee.

Dogs suffer from many more genetic disorders than cats, whereas cats are more likely to suffer from infectious diseases.

As we breed for type, we must remember that we must also accept the problems and conditions that may go with breeding. Perhaps we should not always push for the best specimen, but maybe use other animals in breeding programmes to give a wider gene pool. Shows should also always be run for enjoyment. Breeders have a responsibility to enjoy their animals, but to be responsible about animal welfare and health at the same time. In the end, if breeders do not breed for health, they will have nothing.

Cats are born with PKD cysts. They may just grow in size and/or number as the cat ages. Older cats have larger, more numerous cysts.

Cat owners should have autopsies done on all their animals when they die, as this will give a picture of the prevalence of the disease.

The seminar was concluded at 9.15 pm, with Cheryle U'Ren thanking the guest speakers for providing a most informative account of PKD.

For further information on PKD Click here: PKD Information