Topic: GOOD NEWS - PLL Gene Mutation has been found

[ChaosEmpire]

Susie

I just was told about this already running study about deafness...hmm who has told me that...  :taunt:
Surely I would like to see other DNA test before
Heart, Kidney!!!, but for the moment, i already would be glad to see test results of minis that did echo doppler, UPC and kidney-ultrasound

[Adrian]

when you have a look at the first results, it appears that there isnt many "good" studs with a "clear" status
of course most of the tested are bitches (in fact around 30% are some males) but finally i see only 3 or 4 nice dogs at the moment... (i dont include mine in as he is too big for most of the bitches i know)

it seems that "we" are going to run after the same studs

[ChaosEmpire]

so where is the difference before and after
Posted on: October 10, 2009, 07:58:52 PM37% Clear
58% Carrier
5% At Risk

few dogs later it looks like (63results):

36.5%
58.75%
4.75%

Posted on: October 11, 2009, 01:51:05 PMBtw: Based on all entered Minis (which is surely not a complete list)
we have 4.63% Affected
12,3% are known to be at least carrier(detected based on the affected ones and dna results) 2 carriers are parents, one in average a child, here is the issues cause of a non complete database...else we would have more carrier entries already
the average litter size is somewhat between 4-5, so we will end up at ~ 30%carriers based on affected...
missing still all carriers based on matings without non affected parents

the germany vets have a statistic, there is also ~5% affected, so it seems that this could be the limit for affected ones

[Adrian]

was just to go on with the debate  :buba:

[ChaosEmpire]

hi adrian

thats what i m waiting for...
a debate about breeding, if we will really have 2/3 minis with at least one copy of the gene
the free one will be very valueable

but susie has posted an interesting article, i read month ago, but i only readed it cause of multimating one dame idea, missed some other points in the article
lets hope we will have more clear females than males, as most stud dogs have more matings than females will have litters...

[nobul]

Does it matter ?

You can still use carrier males to clear bitches, or for our country we can still use affected males to Bull terrier bitches, as long as we DONT breed any more AFFECTEDS

SO no more affected to carrier , carrier to carrier or affected to affected these will have a definate outcome

[Tadi]

very good said, Julie!
also my opinion.

[ChaosEmpire]

Both, OFA and AHT, say the same, there is a little rest risk for CARRIER's to get luxated
They cant explain why it is that way, but this is the result of their research

So, if we have the possibility to do a Clear+Clear mating, we shall do it, but surely we can also do Clear+Affected matings, getting a litter with "Low Risk Carrier's"

OFA says 5-10%, AHT says 2-20% risk to get affected for a CARRIER (one single copy of the gene) while assuming it will be more near to 2% than to 20%
So we will have to do further PLL Testing at an eye specialist, also if the dog is tested as Carrier

[Tadi]

know that discussion since some months, but there are only few such cases

so some questions arise:
1. Could it also be SLL (secondary lense luxation) or accidents etc.?
2. Could It be that this some "luxated CARRIERS" in reality have someting other but not "genetic PLL" or perhaps there was a misdiagnosis by eye-vet?
3. If a dog is CARRIER he has only one copy of the mutant gene. So he can have also "free" offspring as well, or not?

Would be interesting to see some official statements from OFA and AHT.

[ChaosEmpire]

tadi, this is what i think too,

new results in the database, now we have 80 results
current percentage

also i remember, i need the results AND pedigree info...
Posted on: October 14, 2009, 01:13:25 AM

Just wanted to post the meaning of words in the database
seems that already some people are coonfused by the word Luxation (DNA)

PLL: Free (DNA)  = Mini with result CLEAR so no copies of the PLL gene at all
PLL: Carrier (DNA) = Mini with result CARRIER / Low Risk so ONE copy of the PLL gene
PLL: Luxation (DNA) = Mini with result AT RISK so TWO copies of the PLL gene

As AHT/OFA state there is a low risk that carriers will get affected, and also there is a chance that a dog AT RISK will never get affected, so hope this stops all confusion

I asked Bryan at the AHT and this is his reply, which does help make a little more sense of it all.

Hi Susie,
It seems you're not alone in the confusion caused by this.
Classically, geneticists, clinicians, and breeders alike have always spoke of dominant and recessive hereditary conditions. In most cases it holds true, such as coat colour variations, but more and more as new DNA tests are developed we are finding that carriers can also become clinically affected. This could be for a number of reasons such as environmental factors, I'll try and explain this below. It's difficult to estimate the percentage risk until you can look across thousands of results, as at the moment we have a statistical risk factor for PLL carriers developing the condition between 2 and 20%. We believe this figure to be closer to the 2% figure, and hopefully we'll see that affect once we've tested lots more individuals.
 
The dog has 78 chromosomes, and these can be split into 38 identical pairs (autosomal), plus two sex chromosomes (XX or XY).
On each of the autosomal pairs there are two copies of that dogs genetic information (genes).
If there is no mutation present on either side, then the dog would be designated [wild type/wild type] or genetically normal for a particular condition. Both "wild type" genes would have the correct information to complete it's function such as protein manufacture.
In the case of a carrier [wild type/mutant] there is a mutation on one of the chromosome pairs and therefore the protein produced by information on one side is different in some way to that of the other. The mutant protein can still have some functionality, and usually this is okay because you still have one chromosome in the pair that has the correct information, but this won't always be good enough for the job required.
In the case of [mutant/mutant] the gene's functionality will either be severely compromised or not serve it's purpose at all.
 
For PLL the mutation produces a shorter protein than it should. Therefore in a carrier you have normal length and short proteins being produced, which depending on environmental factors can have a greater or lesser consequence. This is not definitive and is still open for further investigation, but if the bonds that hold the lens in place are already partially weakened by genetics and considerations such as diet, body condition and trauma play their role, then unfortunately a carrier can easily become clinically affected.
This would also apply to those dogs with two mutant copies, as the shorter protein will still manage to do the intended job, but just not as well.
 
I hope this makes some sort of sense, and will help you to understand the nature of this PLL-DNA test.
 
Best regards,
Bryan McLaughlin

[nobul]

I personally think it is to cover the butts if a carrier luxates .  Remember any dog can luxate due to injury etc. I agree with Tadi.  He is a link that some might find useful, it gives an easy to read guide based on the mendelin theory
http://www.gtpets.com.au/dnatesting/breedingstrategies.php

If we do not use our carriers we might as well stop breeding now as i really think we are going to have a huge amount of carriers

[Tadi]

I am with Adrian on result :unsure:. 

I don't understand why for Mini's we need to look at deafness when very few Mini's suffer with it and many other breeds are already looking. plus it doesn't kill our dogs. I would like to see a DNA test for Hereditary Nephritis (HN), because of the mode of inheritance I really believe if enough BT's & MBT's participate it won't take long to find the DNA test, and then after HN it has to be hearts but that of course is going to be like PLL much more difficult, or maybe PKD.

it is correct.
but i think deafness is a much bigger problem at the Standard Bullterriers than anyone would admit

[ChaosEmpire]

there are several cases of half/deaf minis around
the issue..mostly they are keept silent...

110 DNA Tested Dogs
44 Free / 60 Carrier / 6 At Risk
40,00 % Free / 54,55 % Carrier / 5,45 % At Risk

[Forum Staff]

The AHT has opened the doors...

DNA Test can be ordered via this form:
http://www.aht.org.uk/pdf/pllform.pdf

If you have send DNA for research you can order your results via this form:
http://www.aht.org.uk/pdf/pllresult.pdf

Geneticists identify a mutation for Primary Lens Luxation (PLL) in several breeds.
(September 2009)

A mutation responsible for the development of primary lens luxation in many breeds of dogs has been identified by geneticists working in the Kennel Club Genetics Centre at the Animal Health Trust, led by Dr Cathryn Mellersh, in collaboration with Dr David Sargan (Cambridge University) and Dr David Gould (Davies Veterinary Specialists).

Primary Lens Luxation (PLL) is a well-recognised, painful and blinding inherited eye condition that affects many breeds of dog.  In affected dogs the zonular fibres that support the lens breakdown or disintegrate, causing the lens to fall into the wrong position within the eye.  If the lens falls into the anterior chamber of the eye glaucoma and loss of vision can quickly result.

The team of scientists have identified a mutation that is responsible for the development of PLL in several breeds, including the Miniature Bull Terrier, the Lancashire Heeler, Tibetan Terrier, the Jack Russell Terrier, the Parson Russell Terrier, the Patterdale Terrier, the Sealyham Terrier and the Chinese Crested dog.
A DNA test will be available from Monday 19th October, 2009.

PLEASE NOTE – We have limited resources and regret that we are are unable to consider any requests for this test before October 19th, without exception, and cannot issue any testing kits  before that date.  Testing kits can be requested by  e-mail on or after October 19th to swab.request@aht.org.uk. If you do not have access to email please telephone 01638 555621 or fax 01638 555666.

The DNA test can be used to determine a dog’s genotype with respect to this mutation.  Dogs will be identified as CLEAR (has two normal copies of the gene), CARRIER (has one normal copy and one mutated copy) and AFFECTED (has two copies of the mutation).  Breeders will be given an estimate of each dog’s risk of developing PLL depending on their genotype and will be able to make sensible breeding decisions that minimise the risk of producing dogs that will become affected by this serious and debilitating condition.

Breeders and owners will be able to test their dogs using a simple test kit that will be available from October 19th, 2009.  It will be possible to collect DNA from dogs to be tested via a simple cheek swab which will be included in the test kit, along with all information, necessary forms and full instructions, please click on link http://www.aht.org.uk/genetics_tests.html#canine.

Owners who submitted samples for the PLL research prior to September 1, 2009 may request test results using a form that will become available on this website on October 19th, 2009.  Click on link for form http://www.aht.org.uk/pdf/pllresult.pdf

We would like to sincerely thank all the many owners and breeders, from all over the world, who have contributed DNA and information from their dogs to this project.  This discovery would not have been possible without them.  We would also like to thank everybody who has made a financial donation to support the research.

Primary Lens Luxation

Primary Lens Luxation (PLL) is a well-recognised, painful and blinding inherited eye condition that affects many breeds of dog.  In affected dogs the zonular fibres that support the lens breakdown or disintegrate, causing the lens to fall into the wrong position within the eye.  If the lens falls into the anterior chamber of the eye glaucoma and loss of vision can quickly result.

Scientists at the AHT have identified a mutation that is associated with the development of PLL in several breeds of dog.  The DNA test we are now offering examines the DNA from each dog being tested for the presence or absence of this precise mutation.  It is thus a ‘mutation-based test’ and not a ‘linkage-based test’.

Breeders will be sent results identifying their dog as belonging to one of three categories:

CLEAR: these dogs have two normal copies of DNA.  Our research has demonstrated clear dogs will not develop PLL as a result of the mutation we are testing for, although we cannot exclude the possibility they might develop PLL due to other causes, such as trauma or the effects of other, unidentified mutations.

CARRIER: these dogs have one copy of the mutation and one normal copy of DNA.  Our research has demonstrated that carriers have a very low risk of developing PLL.  The majority of carriers do not develop PLL during their lives but a small percentage do.  We currently estimate that between  2% – 20% of carriers will develop the condition, although we believe the true percentage is nearer to 2% than 20%.  We do not currently know why some carriers develop the condition whereas the majority do not, and we advise that all carriers have their eyes examined by a veterinary ophthalmologist every 6- 12 months, from the age of 2, throughout their entire lives.

GENETICALLY AFFECTED: these dogs have two copies of the mutation and will almost certainly develop PLL during their lifetime.  We advise that all genetically affected dogs have their eyes examined by a veterinary ophthalmologist every 6 months, from the age of 18 months, so the clinical signs of PLL are detected as early as possible.

Breeding Advice

Our research has also demonstrated that the frequency of the PLL mutation is extremely high in most breeds.  This means that allowing only CLEAR dogs to breed could have a devastating effect on breed diversity and substantially increase the likelihood of new inherited diseases emerging.  Therefore, we strongly advise breeders to consider all their dogs for breeding, regardless of their PLL genotype.  GENETICALLY AFFECTED and CARRIER dogs can be bred with, but should only be bred to DNA tested, CLEAR dogs.  All puppies from any litter that has at least one CARRIER parent should be DNA tested, so that the CARRIERS can be identified and followed clinically throughout their lives.  This practise should be followed for at least one or two generations, to allow the PLL mutation to be slowly eliminated from the population without severely reducing the genetic diversity of breeds at risk.
Samples submitted should be cheek swabs (a non-invasive sampling method) obtainable from the Animal Health Trust. Samples should be sent together with a completed DNA Testing form and payment for each sample to Genetic Services, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU. Kits for taking cheek swabs are available by phoning +44 (0)1638 555621 or via e-mail to swabrequest@aht.org.uk.  The price of the test is £40, which includes both VAT and the cost of the sampling kit.    Further information can be obtained by  e-mailing dnatesting@aht.org.uk
will

[Bulli-Mama]

Anyone who can spell it in German?
I unterstand not really all Posts....
and I have a question ...what does it mean on the Form payable cheque? how can I pay the Certificate?
And can I send the Form online or must it be send by Paper Mail?