East Anglian Staffordshire Bull Terrier Club

FOUNDED 1973

HEALTH INFORMATION

PLEASE TAKE THE TIME TO READ ALL THE INFORMATION BELOW - IT IS VITAL IS YOU ARE PLANNING TO BREED FROM YOUR STAFFORD OR LOOKING TO BUY A STAFFORD PUP THAT YOU ARE AWARE OF THESE FACTS!

The SBT Breed Council of GB & NI has produced a Cause of Death Survey which, it is hoped, will be useful in determining anything of significance within the breed. If you have owned a Stafford that has died in your ownership since 1995 please download, complete and return a copy of the survey http://www.staffords.co.uk/health_survey.htm

Notes for the Staffordshire Bull Terrier Breed Club Meeting on Hereditary Cataract (HC) and L-2 Hydroxyglutaric Aciduria (L-2 HGA) (2006)

Dr Jeff Sampson, The Kennel Club

BACKGROUND

Both HC and L-2 HGA are inherited as single autosomal recessive conditions in the Staffordshire Bull Terrier and DNA tests have been developed at the Animal Health Trust to identify both of the mutations involved. This means that a DNA sample from an individual Staffordshire Bull Terrier can be analysed to see whether the dog is clear of, a carrier of, or affected by both of these mutations/conditions. The availability of these two new tests will be of great benefit to Staffordshire Bull Terrier breeders because it will enable them to select against the specific mutations in their breeding programmes and reduce the frequency of both mutant genes in future generations. Obviously, everyone involved in breeding and registering litters of Staffordshire Bull Terriers need to work together to ensure that the breed gains maximal benefit from these new DNA tests.

WHAT HAS BEEN DONE SO FAR?

Following an application from the Breed Council, the Kennel Club has approved an Official DNA Testing Scheme for both HC and L-2 HGA in the Staffordshire Bull Terrier. This means that copies of DNA test certificates that are issued by the Animal Health Trust will be sent directly to the Kennel Club. Test results will then be added to the tested dog’s information on the Kennel Club’s Registration Database. This will mean the test result for that dog will be published in the next available Breed Records Supplement (BRS); it will also appear on any new registration certificate issued for the dog and on the registration certificates on any of the dog’s future progeny. This Scheme is now in operation and the Kennel Club will be issuing a Press Release shortly. In this release, the Kennel Club will invite all those owners who have already had a test done, to send in a copy of the DNA test certificate to the Kennel Club and we will add the information to the dog’s registration database.

THE WAY FORWARD?

Obviously, the first thing that needs to be done is to create an acceptance amongst Staffordshire Bull Terrier breeders that all potential breeding stock should be DNA tested for both conditions before they are bred from. Knowing the result for each test will then be able to better inform the breeder about choosing potential mates.

If a dog comes back clear for both diseases, then there really isn’t a problem because such dogs will have two normal copies of both of the genes involved and can therefore only pass on normal copies to their offspring.

What about if a dog comes back as a carrier, for either or both conditions? Being a carrier means that the dog will not become clinically affected, but it will have one normal copy of the gene and one mutant copy of the gene, and it will pass on the mutant gene copy to approximately half of its offspring if it is bred from. How breeders deal with identified carriers is, of course, up to the individual breeder. Some will say that they will not breed from an identified carrier, and that, of course, is their decision. However, my own view is that too few dogs enter the breeding pool in all breeds and to reduce this even further could be to the long-term detriment of the breed. Indeed, for me, one of the major advantages of having a DNA test is that it allows breeders to breed from identified carriers. However, breeding from a carrier imposes extra constraints on the choice of a mate. A known carrier should not be mated to an untested dog, because that dog could be at least an unidentified carrier, nor should a DNA tested carrier dog be mated to another DNA tested carrier dog. This is because if two carriers are mated together, each puppy will have a 1 in 4 chance of being affected, and this is far too high a risk. However, if a carrier is mated to a DNA tested normal dog, then the first thing to remember is that none of the subsequent litter will become clinically affected, but the litter will be a mixture of normal and carrier puppies. Obviously, the availability of two different DNA tests makes this choice slightly more complex, but not insurmountable.

We now have quite a bit of experience with the use of DNA testing for disease genes in other breeds and the following pattern seems to work exceedingly well to reduce the frequency of the offending disease-causing mutation without removing dogs from the breed’s breeding pool. The following steps should be followed:

All potential breeding stock should be DNA tested before they are bred from.

Identified carriers should not be mated to an untested dog, or to another identified carrier.

Identified carriers can be mated, but only to a DNA tested normal dog. This allows carriers that have qualities that future generations would benefit from, to pass on those qualities, for example good breed type and temperament. Remember, breeders are trying to produce good all round Staffordshire Bull Terriers, so don’t just choose a mate because it is normal with respect to these diseases, that probably will do the breed no favours; try to find a mate that you might have chosen anyway, that is also normal for these conditions.

If breeders choose to mate a tested carrier dog to a normal dog, then they must undertake to DNA test the resultant puppies to identify those that are carriers and those that are normal. The identified carriers should then be endorsed by the breeder, with the KC endorsement, ‘Progeny not eligible for registration’. In other breeds, the cost of litter testing has become an issue, and in these cases what the breed clubs have adopted is that breeders need not DNA test all of the progeny from a carrier X normal mating, but any untested puppies should be endorsed as above.

APPLYING A SIMILAR STRATEGY TO THE STAFFORDSHIRE BULL TERRIER

To my mind, there is absolutely no reason why a similar approach should not be adopted for the control of both HC and L-2 HGA in the Staffordshire Bull Terrier breed. However, I can see at least one complication that needs to be addressed. Thus far, breeding programmes linked to DNA testing for a specific disease-causing mutation have been adopted by breeds that are relatively small, numerically, where most breeders that register their litters with the Kennel Club are members of an appropriate breed club and, commonly, read the dog papers and breed notes. Engaging with these people to inform them about the various proposals has been relatively easy and most, if not all, will have heard of them.

These two new tests are probably the first in a numerically large breed, where significant numbers of breeders registering litters with the Kennel Club will not be members of a breed club and will not, necessarily, be avid readers of the dog press. This, of course, adds a new level of complexity in terms of communicating ideas and schemes to those that need to take the information on board. The one thing that we do have of course is the fact that most breeders are registering their litters with the Kennel Club and new owners are transferring these registrations. The Kennel Club therefore has the appropriate contact details and are thus in a position to disseminate information to these people. We are presently having discussions internally as to how to best achieve this, but there is no reason why we cannot communicate ideas to all those that breed Staffordshire Bull Terriers and register them with us, and get the right messages across with regard to DNA testing.

DNA, DISEASES and DIAGNOSTIC TESTS in the SBT

Introduction

The Animal Health Trust is a charity that has been helping dogs, cats and horses for more than half a century. We provide specialist veterinary clinical, diagnostic and surgical services and our successes in research have ranged from major breakthroughs in anaesthesia and surgical techniques to the development of vaccines against diseases such as canine distemper and equine influenza. Our scientists and veterinarians, many of whom are world leaders in their field, work alongside bringing together a wide range of expertise for a co-ordinated attack on animal diseases and injuries. By publishing scientific papers, speaking at conferences and talking to other veterinary surgeons about the cases dealt with, this knowledge is passed on to benefit the maximum number of animals.

The canine genetics group is a small team of skilled personnel that liases with clinicians, other scientists within and outside the Trust and dog owners and breeders alike. This unique partnership is what makes the AHT’s research and DNA Diagnostic Service so successful. The genetics group strives to understand the genetic basis of inherited canine disease. The long-term goal of the work we undertake is to identify the genetic mutations that cause inherited disease and develop DNA tests that identify those dogs which carry these causal mutations. Breeders can use the information gleaned from these tests to instigate appropriate breeding programmes that avoid the production of affected dogs and aide in the eventual elimination of inherited disease from breeds at risk.

Basic Genetics

Selective breeding for desirable phenotypic and behavioural traits has produced more than 300 distinct breeds of domestic dog worldwide with each breed being defined by a narrow set of specific physical and behavioural characteristics. Not surprisingly, because many of these key features are maintained by crossing closely related individuals, inherited diseases are very common among purebred dogs. Inherited diseases are caused by mistakes (mutations) within the DNA of genes.

Chromosomes

Each dog has 38 pairs of ‘autosomes’ and a single pair of ‘sex chromosomes’ in nearly every cell within its body. The autosomes are the same in males and females whereas females have 2 ‘X’ sex chromosomes and males have an ‘X’ and a ‘Y’ chromosome. One of each pair of chromosomes is inherited from the dog’s mother and the other from its father.

DNA & Genes

The chromosomes are made up of deoxyribonucleic acid or DNA. DNA is a long, double stranded, very complex molecule composed of 4 different building blocks or nucleotides (abbreviated to C, G, T and A). It is divided into ‘genes’; every gene is literally a written instruction that codes for the production of a single protein. There are probably about 30 – 40,000 different genes within the DNA of every dog. The dog has 2 copies (or alleles) of each gene, one on the chromosome it inherited from its mother and one on its paternal chromosome. The proteins that are coded for by these genes interact with one another in very specific ways within the body to perform all the functions necessary for life. The order of As, Gs, Cs and Ts within a gene needs to be exactly right for the cells to make the correct proteins; ‘misprints’ or mutations within genes can lead to ‘faulty’ or non-functional proteins and these, in turn, can give rise to disease.

Inherited Disease in the Staffordshire Bull Terrier

As with other breeds of dog the Staffordshire bull terrier suffers from its fair share of inherited disease. The AHT has been researching the genetic basis of two such diseases over the last few years, Hereditary Cataract (HC) and L-2-Hydroxyglutaric Aciduria (L-2-HGA) and is pleased to announce the development of DNA Diagnostic Tests for both these conditions are now available at the AHT.

L-2-Hydroxyglutaric aciduria

L-2-HGA (L-2-hydroxyglutaric aciduria) in Staffordshire Bull Terriers is a neurometabolic disorder characterised by elevated levels of L-2-hydroxyglutaric acid in urine, plasma and cerebrospinal fluid. L-2-hydroxyglutarate is normally metabolised to a-ketoglutarate but in affected dogs it is not, and builds up in the body with devastating results. L-2-HGA affects the central nervous system, with clinical signs usually apparent between 6 months and one year (although they can appear later). Symptoms include epileptic seizures, "wobbly" gait, tremors, muscle stiffness as a result of exercise or excitement and altered behavior.

Hereditary Cataract

Hereditary cataract in the Staffordshire bull terrier was first reported in the United Kingdom in 1976. The condition is not congenital, so puppies are born with normal eyes, but cataracts begin to appear at a few weeks to months in age, progressing to total cataracts by 2 to 3 years of age. This cataract is always bilateral, symmetrical in the two eyes, and progressive until total with resultant blindness.

Autosomal Recessive Disease

Both HC and L-2-HGA are autosomal recessive conditions. This type of disease is caused by a mutation within a single gene located on one of the 38 pairs of autosomes. Mutations causing recessive diseases can be small (for example a single incorrect nucleotide, or the insertion or deletion of a small number of nucleotides) or large (such as the deletion of a large number of nucleotides). Because the mutations are within genes located on the autosomes both males and females suffer from the disease with equal frequency.

A dog has to have a mutation in each copy of the gene (i.e. the copy on each of its chromosomes) before it will actually develop symptoms of the disease. This is known as being homozygous for the disease allele. If it has one mutated copy of the gene and one normal copy it will be a carrier of the disease but will never actually develop symptoms. It can, however, pass the mutation onto future generations. For a dog to be affected with an autosomal recessive disease, both its parents have to be either carriers or affected. If two carriers are mated together on average one in four of their offspring will be affected, one in four will be genetically clear and half will be carriers.

DNA Diagnostic Tests

After several years of research into the genetic basis of these two inherited conditions the AHT is pleased to announce the identification of the mutations that cause both diseases. The research was made possible by funding from the Kennel Club Health Foundation Fund, the American Kennel Club Canine Health Foundation, the Staffordshire Bull Terrier Breed Council and PetSavers. DNA samples from affected dogs and their close relatives were donated by Staffordshire Bull terrier owners and breeders and the AHT is sincerely grateful to all those who donated samples from their dogs.

How Breeders Can Benefit From the DNA Diagnostic Tests

Owners can now submit a DNA sample from any dog for testing and find out whether the dog is clear, a carrier or affected with either, or both, HC and L-2-HGA. The owner will receive a certificate that states whether the dog is Clear, Carrier or Affected, with the following explanations:

CLEAR: the dog has 2 copies of the normal gene and will neither develop HC / L-2-HGA, nor pass a copy of the HC / L-2-HGA mutation to any of its offspring.

CARRIER: the dog has one copy of the normal gene and one copy of the mutant gene that causes HC / L-2-HGA. It will not develop HC / L-2-HGA but will pass on the HC / L-2-HGA mutation to 50% (on average) of its offspring.

AFFECTED: the dog has two copies of the HC / L-2-HGA mutation and is affected with HC / L-2-HGAand will develop HC / L-2-HGA during its lifetime.

Samples should be sent with a completed DNA Testing Form and a cheque for £67-00 (inc VAT) per sample for Hereditary Cataract or L-2-HGA testing alone, or £112-00 (inc VAT) per sample for Hereditary Cataract and L-2-HGA DNA testing together, to Genetic Services, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU.

DNA testing forms can be downloaded from our web site (http://www.aht.org.uk).

DNA testing forms can also be obtained by contacting Vikki Lett 08700 50 91 44 ext 1223 or via e-mail to dnatesting@aht.org.uk

Blood samples which have already been tested for L-2-HGA can also be tested for Hereditary Cataracts - please provide a completed DNA Testing Form quoting the Sample Number from the L-2-HGA certificate, with a cheque for £67-00 inc VAT. DNA testing forms can also be obtained by contacting Vikki Lett 01638 750659 ext 1223 or via e-mail to dnatesting@aht.org.uk

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The Way Forward

Now that genetic tests are available for both HC and L-2-HGA it is possible to avoid breeding any more dogs that are affected with either of these conditions. Initial L-2-HGA test results indicate that approximately 15% of dogs tested are carriers of the L-2-HGA mutation and it is likely that a similar proportion of dogs will also carry the HC mutation. Some dogs will carry both mutations but as many as 20-25% of Staffordshire bull terriers could carry at least one mutation. Therefore, geneticists at the AHT advise against eliminating carriers from the breeding population because doing so will result in an unacceptable reduction in the gene pool that can never be recovered.

Instead, our advice would be to test all dogs that might be used for breeding, and if a dog is identified as being a carrier of either HC or L-2-HGA they should only be mated to dogs that have tested clear and any resulting puppies that may be used for breeding should also be tested. This practice will allow gradual elimination of the mutations from the breeding population, while also allowing those desirable characteristics exhibited by the carriers to be passed to future generations. As long as carriers are always bred to clear dogs no affected puppies will be produced and although some carriers will be bred they will be perfectly healthy with respect to both these diseases. Below is a list of various combinations of dogs, their expected outcomes, and whether they are recommended:

Combination of Dogs	Outcome	Acceptable Breeding Practice
Clear X Clear	All puppies will be clear No need to test puppies	Yes
Clear X Carrier	50% of puppies will be clear 50% of puppies will be carriers Test all puppies to be used for breeding	Yes
Clear x Affected	All puppies will be carriers No need to test puppies	Yes
Carrier x Carrier	25% of puppies will be clear 25% of puppies will be affected 50% of puppies will be carriers	No
Carrier x Affected	50% of puppies will be affected 50% of puppies will be carriers	No
Affected x Affected	All puppies will be affected	No

The ANIMAL HEALTH TRUST would like to thank the following organisations for contributing funds towards Hereditary Cataract and L-2-HGA research:

The Kennel Club Health Foundation Fund

The American Kennel Club Canine Health Foundation

The Staffordshire Bull Terrier Breed Council

PetSavers

The ANIMAL HEALTH TRUST would also like to express its sincere thanks to all the Staffordshire bull terrier owners who contributed DNA samples from their dogs and who readily shared information about their dogs with us. It would not have been possible to develop either of these DNA tests without their help.

Cathryn Mellersh

L-2-HYDROXYGLUTARIC ACIDURIA (L-2-HGA) - SOME FREQUENTLY ASKED QUESTIONS AND ANSWERS

WHAT ARE THE SYMPTOMS OF L-2?

Symptoms can vary from dog to dog but basically there may be seizures of an epileptic style or you may see a change in the way the dog moves. Often after or during exercise (exercise intolerance), or in stressful situations the dog’s muscles begin to seize up and you would notice stiffness around the hind legs and an arching of the back, resulting in the dog being unable to walk normally. This can range from slight incapacity to almost total loss of co-ordination and the dog having full-blown seizures. There are other possible symptoms you may notice: an apparent loss of recognition of normal surroundings, staring at walls, appearing to have altered behaviour.

MY DOG’S BACK LEGS SHAKE WHEN HE’S STANDING STILL OR HE IS STIFF AFTER EXERCISE – DOES HE HAVE L-2?

Lots of Staffords have ‘muscle tremble’ when they are standing – this isn’t indicative of L-2. If your dog is stiff after exercise ask yourself, has this always been the case or has it happened as he has become older (simple ageing) or following an injury (possible arthritis of a joint).

MY DOG APPEARS NORMAL – SHOULD HE BE TESTED FOR L-2?

If you have no concerns that your dog may have L-2 from the classic symptoms there is NO need to test unless the dog is going to be bred from. ALL breeding stock should be tested prior to the first mating to determine it’s genetic status. You may think that as your dog has no clinical signs of L-2 that you don’t need to test but it is impossible to know whether or not your dog is a carrier of the rogue gene without the DNA test.

IS THIS A PROBLEM IN ONLY SOME BREEDING LINES?

Absolutely wrong! This is a problem in Staffordshire Bull Terriers, within the breed as a whole, not within any particular breeding line. The reason that initially only certain lines were showing the problem is because, having produced affected pups, responsible breeders within those lines joined the research for the DNA test. As testing has become more commonplace L-2 carriers have shown up across the board in various ‘lines’. It is thought that this problem goes back probably over at least eight generations of Staffords – look at the majority of Stafford pedigrees and you will find common ancestry when you start delving back.

WHAT IS THE PROGNOSIS FOR AN L-2 AFFECTED DOG?

L-2 can vary from dog to dog, so in the worst case scenario the severity of the seizures can be so awful that the owner decides the best course of action for the dog is to have it put to sleep to save further suffering. The medication necessary to control the condition is anti-convulsant (phenobarbitone) and therefore strong and powerful, as well as expensive! It also needs to be administered at very regular intervals to have the correct effect. A dog on such medication needs a VERY regular routine to be able to live a normal life. Some more mildly affected dogs have lived without medication, owners dealing with the symptoms by keeping the dog out of stressful conditions, maintaining an even keel so as not to stimulate seizures. Herbal tranquillisers have had effect. Similar to epilepsy, it can be progressive and have spells where the dog remains the same for a period of time, to later deteriorate.

WHAT IS THE DNA TEST?

The DNA test is a one-off test that will determine the genetic status of your dog. There are three possible outcomes of the test. It will be:

CLEAR (UNAFFECTED or NORMAL) - that is NOT affected by L-2, nor a carrier of the mutant gene which produces L-2

CARRIER – that is not affected by L-2 but carrying one copy of the mutant gene, which will be passed on to, on average, 50% of its offspring

AFFECTED – affected by the L-2 condition and carrying two copies of the mutant gene

HOW DO I GET MY DOG TESTED?

Testing is now simple – your vet needs to take 3mls of blood (this can be done while you are at the vet for any other routine procedure) or cheek swabs can be submitted and sent to the Animal Health Trust at Newmarket for DNA testing. The DNA test costs £67 and forms and information on the test can be found on the AHT website http://www.aht.org.uk/pdf/sbtL2HGAwithHCformvat.pdf or by contacting Genetic Services, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU tel: 01638 750659 ext. 1223.

When research was underway urine samples were used to determine whether or not the dog was affected (not for carrier status) – this is no longer applicable.

HOW LONG DOES TESTING TAKE?

Testing can take around six weeks for results to come back so make sure you have submitted samples long before you plan your matings.

WHAT WILL THE RESULT MEAN FOR ME WHEN I AM BREEDING FROM THE DOG?

The result will mean that you can breed responsibly with the knowledge that by making sure you only ever breed clear to clear, or clear to carrier that you NEVER produce affected puppies. If you have a carrier dog and decide to breed from it, the mating MUST be to a clear dog and then you must test all puppies to determine their genetic status. It is sensible to then endorse the registration papers of the carrier pups so that progeny of these pups cannot be registered with the KC and explain the importance to their new owners that they should NOT be bred on from without serious consideration and the necessary responsibility (ie. mating only to a tested clear dog and then testing and endorsing pups). Some breeders may chose to ensure that any subsequent carrier pups will be neutered when they are old enough.

HOW CAN PUPPIES BE TESTED?

Puppies can be tested by submitting blood in the same way as adults. Obviously pups will have to be old enough to have the blood taken, probably around 4 weeks, and it will be necessary to be totally accurate about identifying the individual puppy. It is proposed to begin testing by taking a buccal (cheek cell) swab in the near future. This may be an easier and less traumatic way of testing puppies, again the pup would need to be 4 weeks old to swab.

WILL THE RESULT BE ACKNOWLEDGED ON DOCUMENTATION?

The Kennel Club now ensure that all KC registration documents issued contains the results of L-2-HGA tests. The results are published in the Breeds Record Supplement.

COMBINED GENETIC TESTING

The genetic test for Hereditary Cataract is now available to the public and combined genetic testing for both HC and L-2-HGA will be available at a reduced price of £112 for both tests run at once, as opposed to £67 per test run separately. For anyone who has already submitted blood for L-2 testing, the same blood sample will be able to be used by the AHT for HC testing. If testing is to be done not having previously submitted samples you will need to submit blood for both HC and L2

DNA PROFILING

DNA profiling has been underway for quite a while now as a means of identifying beyond dispute an individual dog’s parentage. Although the DNA for any dog profiled will be recorded it is not possible to use this for genetic testing. Each test requires specific differing methods of extracting the DNA, therefore separate swabs would need to be used.

IDENTIFYING DOGS

It is advisable to ensure that individual dogs are microchipped, then when samples are taken for genetic testing, whether by blood or swab, the details of the microchip can be entered on the accompanying form. Although it will be possible for swab kits to be sent out to individuals for ‘home use’ it may be best if the swabs are actually used under veterinary supervision for third party integrity and also to ensure that the swabs are used correctly. If the swabs aren’t handled properly you will find they are returned – another length of time before you will get your result! It will be essential that any litters of puppies DNA tested are identified accurately. If pups aren’t obviously different by their coat markings they could wear differing coloured collars, have differing coloured nail varnishes applied to nails on one foot or perhaps cut a small piece of fur from differing areas of the coat. It is also possible (and more reliable) to microchip puppies from 4 weeks for definitive identification

THE FUTURE

In an ideal world we should all use DNA testing on all our breeding stock from now on, mate only clear to clear or clear to carrier then test pups. It is unlikely that many people will choose to mate carrier dogs, partly because of the expense involved in testing a whole litter (£67 per pup). In this way within a few generations the condition will become self-limiting and carriers would be phased out. It must be accepted that only responsible breeders will use the test, leaving the rogue gene still out there unseen.

In the future once the Kennel Club registration documents contain the result of L-2 testing it will be accepted that pups bred from two L-2 tested clear parents will be hereditarily clear and recorded as such without need for further testing.

The SBT Breed Council organised two seminars held in January 2006, one in the North of the country, near Bolton, and one in the South, near Watford to explain how to use the DNA testing for responsible breeding. The notes below are from one of those seminars – some of the points raised may now be outdated but are included here for information:

Here are some questions and answers from the first of the BC seminars held on Saturday 21st& 28th Jan 2006

Q. Australia wants to know when the test will be available over there. i.e. when can their own people do it.

A. We have already received 53 samples from Australia and 8 from New Zealand. However, we appreciate that there are problems in sending blood samples from Australia and we are trying very hard to get the L2HGS test to work on swabs. To this end we have conducted a trial on swab samples received from Australia. That trial is now near to completion and we will have further information available at the seminar

Q. As a percentage how accurate are the results and can you clarify the percentages quoted for the likelihood of offspring being carriers, clear and affected. People have commented to us that they know of carrier-to-carrier matings and non-affected puppies being born resulting in more doubts being cast

A. For both the HC and the L2HGA tests the mutations we have identified, upon which the tests are based on, account for all the cases identified thus far. This means we haven’t yet come across a dog affected with either HC or L2HGA that our tests wouldn’t have identified as affected. So, in those terms, it is 100% accurate. It is, in theory, possible for new mutations to arise that cause other forms of HC or L2HGA. This is unlikely, but formally possible. However, even if new mutations did arise it wouldn’t mean the current tests were worthless – it would just mean we would have to develop additional tests.

But it is entirely possible for carrier-to-carrier matings to produce unaffected offspring. Each puppy has a 1 in 4 chance of being affected if both its parents are carriers – so it has a 3 in 4 chance of being either clear or carrier with no symptoms of the disease. Therefore a litter of 4 puppies from a carrier x carrier mating will have about a 1 in 3 chance of having no affected dogs in it.

Q. How accurate is the test for crossbred Stafford's, or so called Stafford's that have some alien blood in there breeding.

A. The tests are both just as accurate for crossbreeds as for purebred dogs in that they will detect the presence of absence of the disease-causing mutations in mutts as well as in purebred dogs. However, they will not detect the presence of other mutations that cause similar diseases that may have come from the other breeds involved. For example, if a dog is a cross between a SBT and a Golden retriever, both of which suffer from HC, the AHT’s HC test can only detect the presence of the SBT HC mutation because the GR HC mutation is currently unknown. So if the dog has been unlucky and has inherited both the SBT mutation and the GR mutation the AHT test will only detect the SBT mutation. But if the 2 mutations are different it is unlikely one copy of each will cause a dog to be affected with HC – usually a dog needs 2 copies of the same mutation to be affected.

Q. What is the actual incidence/percentage of Stafford's exhibiting full-blown symptoms of L2.

A. The exact figure is unknown. In a study we carried out at the AHT we found 25 out of 80 dogs were carriers of the L2HGA mutation. If this figure is extrapolated to all SBTs it would mean close to 2.5% of dogs would be affected. However, the 80 dogs we examined were not a completely random selection of SBTs (they has all be recruited for the HC study) so the real percentage of affected dogs is probably somewhat lower than 2.5% - but still considerably higher than initially thought.

Q. How many dogs have been tested and what percentage are carriers?

A. For L2HGA we have tested over 600 samples, and about 15% are carriers.

Q. What measures will you take in the future to make the test more secure as some feel it's open to abuse or misuse.

A. The security of DNA testing is something that should be fully discussed between breeders and the Kennel Club and the AHT is very interested in hearing all arguments. But until micro chipping is mandatory, and unless vets are going to take every sample to be tested and verify the dog’s ID at the time of sampling it will be difficult to prevent all misuse.

Q. Why are the AHT going to accept mouth swabs for HC test? Isn't this type of sample easier to tamper with than blood samples?

A. Our experience is that breeders prefer mouth swabs. The AHT offers testing from swabs because it there is a greater take-up if that is the case and therefore the disease gene will be eradicated from the population within a shorter period of time.. As for the previous question the AHT will heed all arguments regarding security, but the benefit to the breed in general should also be weighed into the argument. In other words, is it better for the breed to offer swabs, and have a greater percentage of the breed tested (and accept that a small percentage of the results might be false) than have a lower percentage of the breed tested?

Q. At what age does it show when pups are affected and what are the first signs of L2?

A. Clinical signs usually appear when the dog is between 6 months and 1 year old. Affected dogs present with one or more clinical signs of epileptic seizures, incoordination, tremors, muscular stiffness at exercise and altered behaviour.

Q. Will the cost of the tests ever come down?

A. The cost of the test reflects the amount of work necessary to carry out and administer the testing and is comparable with charges for other tests.. There are no plans currently to increase the price.

Q. Can future tests of HC and L2 be done from the same sample for a reduced fee?

A. The current cost of having both tests done on a single sample is £100, which is compared to the cost of £60 for an individual test.

Q. When will it be possible to test frozen semen for L2 and HC?

We can extract DNA from semen in other species and should be able to from dogs. We will accept semen samples, as a trial. Each sample will have to be processed individually so there will eventually be an extra charge for semen; however we are prepared to test semen initially at the same price as blood.

Q. Are there any plans to halt testing whilst some form of ID DNA profiling system is put in place?

A. No. This question seems to refer to the security issues already raised. These will need to be fully discussed between breeders and the Kennel Club.

Q. How do you work out your percentages for inheritance?

A. If the question is referring to the percentages of affected, carrier and clear pups we expect from particular matings – these are calculated by assuming each parent has two copies of piece of DNA that causes the disease (each copy can be normal or mutant) and each parent passes one of the 2 copies to each of their offspring. The copy they pass is random. The same applies for each parent. So, for example, lets assume 2 carriers are mated together. Each of their puppies has a 1 in 2 chance of inheriting the mutant DNA from their mother and a 1 in 2 chance of inheriting the mutant DNA from their father. The chances of the puppy inheriting the mutant DNA from both parents is therefore a half times a half (0.5 x 0.5) which is 1 in 4 (or 25%).

Q. If L2 came from an apparently normal dog and it mutated once to give us the L2 we know now what is to say in 5 or 10 years it will mutate again? Could we be breeding dogs that have been tested for this particular muted gene for the present L2 and have no idea that there is another form rearing it's ugly head?

A. It is formally possible that a new mutation could occur, that is different from the one we have identified, that also causes L2HGA. And this is known to have occurred in some breeds. For example Boston Terriers suffer from two forms of cataract…one is the juvenile/early onset form that is caused by the same mutation that causes HC in the SBT and the other appears later in life and is caused by a different (as yet undiscovered) mutation. These two forms of cataract are caused by different, randomly occurring, mutations. But this kind of thing is very rare and the chances of it happening are very small. Because this L2HGA mutation has arisen once in SBTs doesn’t make it any more likely to occur again. All mutations are random events and are not controlled by mutations that have arisen in the past.

Q. Being that L2 has come from a mutated gene in the past what are the odds of the same gene being mutated in a DNA tested clear dog?

A. This sounds like the same question to the previous one.

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