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! |
NEWS ABOUT PHPV.....................................please read the following
UPDATE FROM BREED COUNCIL GENETIC RESEARCH SUB-COMMITTEE
The uptake for both L-2-HGA and HC DNA tests has been very good with numbers as follows:
L-2-HGA
normals 1808
HC
normals 1151
There have been two changes to the way
samples are taken from the time the tests were made available. Initially DNA was extracted from blood samples
only but as a result of requests from owners the Animal Health Trust developed tests by
way of DNA extraction from check swabs i.e. saliva. However the Animal Health Trust has
just recently decided to discontinue testing from cheek swabs and I quote from a mail from
Nigel Holmes at the AHT “the problem is that the swabs did not give good yields of
DNA for testing so we had to keep going back to owners asking for further samples.” So although it is less convenient for owners to
have to have blood taken, the time taken to eventually receive a result is shorter if retests aren’t required. The reliability of
those results already taken from cheek swabs is not in question.
One disappointment for us so far has been
that the results of tests had not been getting through in to the public domain by way of
the Kennel Club website. We have been chasing
the KC regarding this issue which has been having it’s website updated and now that
the new KC web site is up and running the results are being published. Looking at the website as I write, the list
doesn’t have the numbers that are quoted above but no doubt that will happen in due
course as the figures look as though they are being updated quarterly.
We have also been working with the AHT
looking at ways to improve their service to overseas countries.
The Animal Health Trust has recently been in contact
saying that they can now start to look at a test for PHPV. They have had discussions with
a researcher looking at a similar condition in humans (this is a similar scenario to the
research path for L-2-HGA) and have asked if our owners would send blood samples to them
to begin a project for PHPV. I have already forwarded an article from Cathryn Mellersh to
Breed Club Secretaries for inclusion in Newsletters and Club magazines giving details of
requirements. Hopefully, because we’ve essentially “ been there, got the T
shirt…” our owners will be more acquainted with the idea than before and not
need any motivating. Please encourage owners to help out.
We don’t know how PHPV is inherited so in one respect the research may not be
so straight forward as HC and L-2-HGA, on the other hand because understanding is
improving and there is experience to fall back on and things could happen sooner. No funding is being asked from us for this
condition.
Lesley McFadyen has given details about
registering a litter bred from a carrier for L-2-HGA. Blood samples were taken from
puppies at 4 weeks of age, endorsed registration documents were returned by the time the
puppies were 7 weeks old. She sent the registration forms accompanied by a covering letter
explaining that the puppies had been sampled for L-2-HGA. The KC held on to registration
documents until the results were received, once test results had been confirmed they were
forwarded to Lesley. The documents had all the relevant information regarding genetic
status printed on them. She also had the registrations endorsed “progeny not
eligible for registration” which she alone can lift if required. From a later litter
Lesley has also experienced having registration endorsed hereditarily clear with the
genetic status of puppies, sire and dam printed on the documents, again in good time for
puppies going to their new homes. So the KC and AHT have been up to the mark regarding
fast tracking of registrations. Further details can be obtained from Lesley if
required.
DNA TESTING FOR L2HGA AND HEREDITARY CATARACTS IN STAFFORDSHIRE BULL
TERRIERS
In April 2006, the Animal Health Trust began accepting cheek swabs for the above tests.
Genetic Services Manager
Notes
for the Staffordshire Bull Terrier Breed Club Meeting on Hereditary Cataract (HC) and L-2
Hydroxyglutaric Aciduria (L-2 HGA)
Dr Jeff Sampson, The Kennel Club
WHAT HAS BEEN DONE SO FAR?
THE WAY FORWARD?
 |
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. |
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
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.
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.
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.
A. For L2HGA we
have tested over 600 samples, and about 15% are carriers.
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?
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.
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.
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.
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.
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%).
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.
A. This sounds like
the same question to the previous one.
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: