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Eileen Stein

Report on the EAOD Research Project

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With the little bit of info that's been spoken of lately..can anyone tell me what other tests are a 4 snps and a risk predictive test? Would the risk predictive be along the lines of the 4 grades of cea, your affected, but to what degree depends?  Will this test only be predictive, not absolute?

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Within the past week, Genoscoper began to add a test for EAOD to their test panel for Border Collies in MyDogDNA (Europe; www.mydogdna.com) and Wisdom's Optimal Selection (US; www.optimal-selection.com).  They have not yet had time to add this test to their list of Border Collie tests on their websites.  Nor have they had time to inform all personnel of the new addition, which probably accounts for the varied answers people have received when contacting them directly by telephone or email.  I think they were not prepared for the level of intensity, urgency and initiative among US Border Collie owners.
 

The researchers have narrowed the search for the causative mutation down to one gene and to four tightly linked variants within that gene, and those four variants (markers) are what the test will be based on.  A single causative variant has not yet been identified, although work is continuing intensively toward that end.  It was thought that could be done before the test was offered, and therefore that the findings could be submitted for peer review and publication before the test was offered, but despite further intense work on the project, that has not happened.  As time passed, the balance between the benefit of making a test available asap vs. the benefit of identifying the causative variant before offering the test shifted more and more toward offering a marker test now, which is what is being done.  Marker tests have been utilized before -- IIRC, the test for TNS was a marker test when first offered, although now it tests for the causative variant itself.  But it's important that the nature of a marker test and its implications be well understood.
 

ABCA HEF has expressed reservations before about marker tests.  The HEF board of directors is currently preparing a statement on the new test, including recommendations on how the test should be used for breeding decisions.  When completed, it will be posted on the HEF website.  In the meantime, I will try to answer some of the questions raised based on my own knowledge of the research and the test.
 

The mode of inheritance of EAOD is autosomal recessive; however, not every dog who carries two copies of the variants tested for will suffer early hearing loss.  In the material Genoscoper/Wisdom will be supplying along with the test result report, this is described as incomplete penetrance.  It is similar to CEA in this respect, since not all dogs who are homozygous for the causative mutation for CEA will have vision defects.  Although they carry the mutation and will pass it on to their offspring, some of them -- usually termed "go normals" -- have normal vision throughout their lives and usually cannot be distinguished from homozygous normal dogs by physical examination of the eyes.
 

Until peer review and publication of the research occur, Genoscoper and Optimal Selection (Wisdom) will be the only ones offering this test and its results, and they offer it only as part of their Border Collie breed panel, not as a stand-alone test.  This may cause a hardship in individual cases, where people have already purchased the other tests through a different testing lab's Border Collie package, and that may cause some people to postpone ordering the test at this time, at least in the case of dogs whose pedigrees show no indications of EAOD.  In any case, it is a relatively short-term hardship: It likely won't be long before publication and the test's being offered by other testing labs, and it won't be that much longer before the current, tested-elsewhere dogs age out, replaced by younger dogs who have not yet had test panels done anywhere.
 

Offering breeding advice here will be tricky.  In addition to the uncertainty, however small it might be, that's attached to a marker test as opposed to a test based on the causative mutation itself, there are at least two other factors that must be taken into account here.  One is the carrier rate -- what percentage of our dogs are carrying a single copy of the variant mutation?  The other is the rate of penetrance -- what percentage of our dogs who are carrying two copies of the variant mutation actually suffer early hearing loss?
 

When it comes to breeding, we must always be mindful of balancing the risks of producing affected dogs and spreading a disorder throughout the gene pool against the risks of losing genetic diversity and valuable working traits if too many dogs are excluded from breeding.  Obviously, a very different breeding strategy would be indicated if the carrier rate was very high and the rate of penetrance was very high, than if both rates were very low.

As regards the carrier rate, the researchers have found the overall rate among all dogs tested to be around 35%, which is surprisingly high, given the number of dogs apparently affected by EAOD.  HEF has asked to have the figures for North American dogs broken out separately, so we can see whether their carrier rate differs from the overall pool of dogs tested.

Again, HEF is working on a statement regarding the test and will be publishing it as soon as possible.

 

 

 

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Thank you Eileen...not even sure where to begin with questions but truly appreciate the statement and information..

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Thank you for the information. I really do appreciate it. 

I think I need a lesson :).

Are each of the 4 variants inherited separately or as a group? 

Will the test show the result for each of the 4 markers separately? Or a single result of normal, carrier or affected result? 

If one, some or all of the markers are present in one or both of the parents of a litter, then every one of their pups need to also be tested to give their buyers some idea of risk? 

I disagree that is 'may' cause hardship to some. It is 2-3 times more costly then the market value of a single stand alone charge and nothing about that is fair to anyone who wants or needs this test. There are many many labs that would offer this test as both stand alone or/and as part of a panel, charged at the going market rates. Can ABCA now put a fixed time limit (6 months, 1 year, 5 years, 10 years) before the test information will be made available to another lab that will offer a fair price for single test?  

Edited by backtoblack
clarification of idea

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One other question which has been implied or at the very least been suggested as a possibility by some (not me). Is there any plan to obtain patent?  It would be good for this to be known, one way or another. 

 

Edited by backtoblack
spelling

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The US Supreme Court ruled genetic tests cannot be patented; which is why other companies besides Optigen now provide a test for CEA.  This has been addressed by Eileen several times 

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Thanks Mark, I am aware of that.

However this rumor has stated that the method (perhaps they mean method to find the DNA? or other process) and not the DNA mutations themselves, is what is being patented. So there is no plan to patent methods or other related? Tks 

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On 6/25/2019 at 4:55 PM, backtoblack said:

Thank you for the information. I really do appreciate it. 

I think I need a lesson :).

Are each of the 4 variants inherited separately or as a group?

 Because of their tight linkage, they have been inherited as a group in every dog tested so far, and there is a likelihood (but not a certainty) that they will always be inherited as a group.

Quote

Will the test show the result for each of the 4 markers separately? Or a normal, carrier or affected result?

The results will be given as Clear, Carrier, and At Risk.

Quote

If one, some or all of the markers are present in one or both of the parents of a litter, then every one of their pups need to also be tested to give their buyers some idea of risk?

AFAIK, that's true.  Only if both parents test Clear would Genoscoper say that there is no need to test the pups.

Quote

I disagree that is 'may' cause hardship to some. It is 2-3 times more costly then the market value of a single stand alone charge and nothing about that is fair to anyone who wants or needs this test. There are many many labs that would offer this test as both stand alone or/and as part of a panel, charged at the going market rates. Can ABCA now put a fixed time limit (6 months, 1 year, 5 years, 10 years) before the test information will be made available to another lab that will offer a fair price for single test?  

It seems to me it's a hardship only to those who have already had a panel done elsewhere on a particular dog.  There are some testing labs (not "many," at least in the US) that offer individual test rates as well as panel rates, and some that offer a variation ($X for the first test, and somewhat less if a second tests is ordered, etc.), but $110 is very reasonable for a complete (except for CEA) panel, and my guess is that you will rarely be charged less elsewhere for the handful of tests that any careful Border Collie breeder would want.  And more and more testing labs are going to a breed panel system, because adding an additional test in such cases is a minimal expense, and for a company that has the resources and capabilities of running all existing tests on a dog (as Genoscoper/Wisdom does) the research benefits are enormous.  This said, I hold no preference for labs that offer panel testing only -- just recognizing the realities.  HEF did insist that the researchers publish their results for the very reason of ensuring that no one testing company could have a monopoly on a test.  I cannot predict when publication will occur in this case -- I don't believe anyone involved could do so --  but I strongly believe it will be within 6 months and I feel sure it will not be multiple years.

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The methods used to amplify specific DNA sequences is under patents and licensed to many manufacturers of dna tests

the dna chips used to detect specific DNA sequences are manufactured by 2 or 3 companies and sold for used to other companies 

All a company will need is the DNA sequences and they will be able to develop a test using their preferred dna chip or dna testing technology 

 

question for you, were these rumors started by people who work at genoscoper or at least in the dna testing field or by those who like to postulate conspiracies?

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29 minutes ago, backtoblack said:

One other question which has been implied or at the very least been suggested as a possibility by some (not me). Is there any plan to obtaining patent?  It would be good for this to be known, one way or another. 

 

Happy to have an easy question to answer. :)  There is zero possibility that this test will be patented.  As part of the conditions for HEF's grant to the researchers, they agreed that they would not seek a patent on any results of the research.

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How did they determine a 35% carrier rate? I'm having a hard time understanding or figuring out where they got this number.

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"  The other is the rate of penetrance -- what percentage of our dogs who are carrying two copies of the variant mutation actually suffer early hearing loss?"

 

How do we find this out? Are there any in the research that BAER tested normal yet per their results should be at risk?

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frequency rates are determined by the genetic results in the dogs tested

35% of the dogs tested were heterozygous for the risk variants 

 

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11 minutes ago, Journey said:

 

How do we find this out? Are there any in the research that BAER tested normal yet per their results should be at risk?

We let the researchers complete their ongoing studies which are funded by the hef

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Were they sent any samples of normal dogs though? Or as normal as can be determined via BAER testing and knowing they were not related to any known pedigree of affected..Just wondering if the figure is skewed based on what they had to begin with.

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Is the gene involved, and the 4 markers different than what ProjectDog determined years ago?

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2 hours ago, Journey said:

Is the gene involved, and the 4 markers different than what ProjectDog determined years ago?

We have no way of knowing this, because projectDOG did not share the identity of their test variants with us.  

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On 6/25/2019 at 11:10 PM, Eileen Stein said:

We have no way of knowing this, because projectDOG did not share the identity of their test variants with us.  

Has the univ of Finland group shared their data yet?

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Some of your questions may be answered in the published EAOD study which included the univ of Finland group:

Variation in Genes Related to Cochlear Biology is Strongly Associated with Adult-Onset Deafness in Border Collies, 2012,

https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1002898

 

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Ok, how does something from 2012 relate to what is now being told to people? The test is available. So, did they share with the HEF their data - for this test?

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You asked questions on test methodology, hearing controls, etc.; these are addressed in the methods and materials section of publications.

how to use the test results is what you need to know; as Eileen stated we’re working on it.  They have shared confidential details with which we will develop our recommendations.  Do you really need to know all the other details you’re asking about?

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Karen,

I know you mean well, but you’re wearing everyone out with all these questions.  The HEF is a volunteer board. Completely volunteer, concerned breeders, like yourself.  Questions are fine, but there is a limit where answering every little question becomes burdensome. We all have the same goal, we just need to breathe a little. 

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