Eic In Labradors

[Wyn]

With -- based on the statistics Sylvia posted -- 50% of dogs being carriers or affected,

Not speaking for Sylvia, but she typed 60% carrier, which should mathematically translate to 8% affected, but the latest figures showa higher total in Australia.

Sylvia's numbers:

(700 affected +2595 carriers) /6959 total =47% affected or carriers

. . . but 40% or 60%, the point is the gene is widespread and the decision to breed it out will mean dropping a lot of dogs from the gene pool.

Hells bells - serves me right for quoting from memory. I have found the email (dated Sep 1) with the Aus numbers in it:

98 tested

51 carriers 52%

23 affected 24%

24 clear 24%

BUT - remember these are really skewed as there has been an influx of presumed DNA affecteds (ie dogs that have collapsed) and their relatives and also it is a really small sample. The figures from U Minn are much closer to the mark.

Yes, SG I have seen dogs collapse with EIC. I had a bitch collapse several times in the mid nineties; try as I might I couldn't get to the bottom of what was going on. I sent blood to Susan Taylor for the original research, however was told my bitch can't have had EIC as they were working with US field trial lines and my bitch's pedigree was so far removed from those as to be of no use. Rather unscientific I thought, but there you go.

Having been cleared from all known genetic issues at the time, that bitch had three litters; there has been no report of collapsing dogs amongst her offspring, however her daughter came back DNA affected (as of course did she). They are boarding with me at the moment - the collapsing bitch turns 15 next January.

We now know what her issue was, however I concur with SG and BlackDog's concerns re making rash decisions based on the EIC DNA test. For me, PRA is almost a non issue now - yes, there are still a few carriers around and I would certainly use them if I thought they were the best choice, assuming the partner was clear. In fact I have a carrier bitch (daughter of my Master Mariner son Pete, who was a carrier) who I'm waiting to mate next season. She's also an EIC carrier, which is making life interesting

Sylvia

Well I will throw a spanner into the works, personally I think we are getting too far from what some of the really nasty problems in Labradors are, epylipsy(sp) being the top of my list. I own 2 imported chocolates from the UK both are EIC clear, I have just tested a 10 week old dog pup from a Frozen semen litter (UK) I was testing him for colour PRA etc so got EIC done as well, he came back clear as well as did his litter brother. My dogs hunt, really rough shooting to boot, they run all day, no one as yet has collasped. The only reason I tested them as 1) their DNA was already in Australia and 2) a litter by one of them had 2 carriers in that litter, I guess if he is clear then it come from their mother. I might consider testing other dogs (stud) if a bitch owner requested it, but at this point in time I think it is all a bunch of cobblers, and just another test for someone to make money on. I don't know about other Labrador breeders whom have had Labradors for years and years, but I don't see a rash of collapsing everywhere and didn't years ago either, Interesting that Master Mariner was a Carrier, I have Master Mariner in all my pedigrees and as yet not problems or they have been tested clear, does anyone really know the mode in inheritence.

[Wyn]

With -- based on the statistics Sylvia posted -- 50% of dogs being carriers or affected,

Not speaking for Sylvia, but she typed 60% carrier, which should mathematically translate to 8% affected, but the latest figures showa higher total in Australia.

Sylvia's numbers:

(700 affected +2595 carriers) /6959 total =47% affected or carriers

. . . but 40% or 60%, the point is the gene is widespread and the decision to breed it out will mean dropping a lot of dogs from the gene pool.

Hells bells - serves me right for quoting from memory. I have found the email (dated Sep 1) with the Aus numbers in it:

98 tested

51 carriers 52%

23 affected 24%

24 clear 24%

BUT - remember these are really skewed as there has been an influx of presumed DNA affecteds (ie dogs that have collapsed) and their relatives and also it is a really small sample. The figures from U Minn are much closer to the mark.

Yes, SG I have seen dogs collapse with EIC. I had a bitch collapse several times in the mid nineties; try as I might I couldn't get to the bottom of what was going on. I sent blood to Susan Taylor for the original research, however was told my bitch can't have had EIC as they were working with US field trial lines and my bitch's pedigree was so far removed from those as to be of no use. Rather unscientific I thought, but there you go.

Having been cleared from all known genetic issues at the time, that bitch had three litters; there has been no report of collapsing dogs amongst her offspring, however her daughter came back DNA affected (as of course did she). They are boarding with me at the moment - the collapsing bitch turns 15 next January.

We now know what her issue was, however I concur with SG and BlackDog's concerns re making rash decisions based on the EIC DNA test. For me, PRA is almost a non issue now - yes, there are still a few carriers around and I would certainly use them if I thought they were the best choice, assuming the partner was clear. In fact I have a carrier bitch (daughter of my Master Mariner son Pete, who was a carrier) who I'm waiting to mate next season. She's also an EIC carrier, which is making life interesting

Sylvia

Well I will throw a spanner into the works, personally I think we are getting too far from what some of the really nasty problems in Labradors are, epylipsy(sp) being the top of my list. I own 2 imported chocolates from the UK both are EIC clear, I have just tested a 10 week old dog pup from a Frozen semen litter (UK) I was testing him for colour PRA etc so got EIC done as well, he came back clear as well as did his litter brother. My dogs hunt, really rough shooting to boot, they run all day, no one as yet has collasped. The only reason I tested them as 1) their DNA was already in Australia and 2) a litter by one of them had 2 carriers in that litter, I guess if he is clear then it come from their mother. I might consider testing other dogs (stud) if a bitch owner requested it, but at this point in time I think it is all a bunch of cobblers, and just another test for someone to make money on. I don't know about other Labrador breeders whom have had Labradors for years and years, but I don't see a rash of collapsing everywhere and didn't years ago either, Interesting that Master Mariner was a Carrier, I have Master Mariner in all my pedigrees and as yet not problems or they have been tested clear, does anyone really know the mode in inheritence.

OOPs , me bad, you haven't said Master Mariner was a carrier, but I did hear that some where, not that it would make any difference, every dog has to be judged on its merits and what that dog can bring to your kennels.

[Lablover]

epylipsy(sp) being the top of my list.

Further to (clinical) notes sent with EIC samples tested in the US, atypical epilepsy etc.

http://www.cvm.umn.edu/VBS/faculty/Mickels...lapse/home.html

Lablover who likes to keep with the latest research. Being a computer dunce, need to add links in next thread.

Edited November 22, 2009 by Lablover

[Lablover]

Sorry duplicated.

Edited November 22, 2009 by Lablover

[Lablover]

First example, incorrectly labelled as EIC.

Second example, note accent.

http://s303.photobucket.com/albums/nn122/j...nt=525d71c4.pbr

Third.

http://s23.photobucket.com/albums/b351/jes...rrent=Leela.flv

[Wuppywoman]

There is some interesting discussion re this issue. When I say I am going to test I am doing it prepared for the results. If my dogs are carriers I will not completely change the direction of my breeding program but breed carrier to clear and test the offspring. I have a black litter due in December and will be testing any show quality girls for colour and EIC as some will carry choc and some yellow and choc. Hopefully I will have a girl not carrying yellow who is EIC clear. (fingers crossed lol) Having said that if there is a stunning carrier pup I will keep that puppy and breed to a clear dog in the future. I am concerned about the reliability of the test etc but I will see what the results have to say and reconsider my position from there. I feel it is good idea to know if it is there in my lines or not. I agree there are many other issues affecting our breed that are more important right now and that someone is definately making money from all these tests. I just want to know out of interest that status of my dogs and see what future delvolpments bring. No I have never seen a collaspsing dog.

[MissMonaro]

When looking into EIC (some referred to it as heat stroke or a form of epilepsy), years ago, I thought Australia was relatively safe (but had heard otherwise).

Interesting.

I actually know of a couple that bought a pair of litter mates. Not sure which bit below happened first as it was many years ago...

1. Taken in for desexing....one, no probs....but there were complications with the other one and she was pulled out of the operation and not desexed. I think she had a fit.

2. One particularly hot day, they took them to the beach.....brought them home and the same one above had another fit.

Apparently not the first time, as she had had minor quirky things before, like being exhausted and collapsing...but never fitting.

The vet did do tests for epilepsy, but I think the prognosis was inconclusive.

Now I am wondering if it possibly was in fact EIC.

[sandgrubber]

The vet did do tests for epilepsy, but I think the prognosis was inconclusive.

Now I am wondering if it possibly was in fact EIC.

To my understanding, there are is test for epilepsy. It is idiopathic. Diagnosis involves ruling out other possible causes. Prognosis is usually inconclusive unless seizures re-occur in a pattern that fits the disease description. The symptoms you describe don't fit the excited state associated with EIC . . . could also be atypical epilepsy. Hopefully the U. Minn mob will succeed in finding the gene for this and we will end up being able to test.

[Lablover]

The vet did do tests for epilepsy, but I think the prognosis was inconclusive.

Now I am wondering if it possibly was in fact EIC.

To my understanding, there are is test for epilepsy. It is idiopathic. Diagnosis involves ruling out other possible causes. Prognosis is usually inconclusive unless seizures re-occur in a pattern that fits the disease description. The symptoms you describe don't fit the excited state associated with EIC . . . could also be atypical epilepsy. Hopefully the U. Minn mob will succeed in finding the gene for this and we will end up being able to test.

Miss Monaro, I am no vet!!! If you like add current-condition, symptoms, medical treatment and age.

Some autoimmune, TVD?? At least with the EIC test, this particular disease can be discounted.

Maybe someone who has or had a labrador with epilepsy can add to this or another thread.

[MissMonaro]

Lablover - unfortunately I havent spoken to the ppl in quite a while, so dont really know what ever happened.

There was no "known" epilepsy in the lines at all.

Of course, there were other factors that could account for the problem .eg. the owners told me she often jumped the fence and got out of the yard and I mentioned that maybe she had been hit by a car and perhaps had a screw loose in the brain. They didnt think that was it - but you have to look at all possibilities.

But anyway, it was the comment about EIC being similar to heat stroke or a form of epilepsy that caught my attention and made me remember these dogs.

[Lablover]

Lablover - unfortunately I havent spoken to the ppl in quite a while, so dont really know what ever happened.

There was no "known" epilepsy in the lines at all.

Of course, there were other factors that could account for the problem .eg. the owners told me she often jumped the fence and got out of the yard and I mentioned that maybe she had been hit by a car and perhaps had a screw loose in the brain. They didnt think that was it - but you have to look at all possibilities.

But anyway, it was the comment about EIC being similar to heat stroke or a form of epilepsy that caught my attention and made me remember these dogs.

Linked atypical epilepsy, in labradors is presumed to be an autosomal recessive...thus possibly "more" difficult to follow on pedigree analysis without full disclosure/open data bases.

As EIC has the same mode of inheritance, (as does PRA), may researchers and scientists develop further DNA tests.

[zenchel]

To my understanding, there are is test for epilepsy. It is idiopathic.

To my knowledge, there is no test for epilepsy in ANY breed, least of all Labradors. The above quote is contradictory.

"Idiopathic" - adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. (Wiki)

If the cause is spontaneous or unknown, how can there be a test for it? I am aware of research on tests for epilepsy, however I don't believe there has been any breakthrough yet, particularly in Labs.

Linked atypical epilepsy, in labradors is presumed to be an autosomal recessive...thus possibly "more" difficult to follow on pedigree analysis without full disclosure/open data bases.

As EIC has the same mode of inheritance, (as does PRA), may researchers and scientists develop further DNA tests.

If epilepsy is autosomal recessive in Labs, then I'm a monkey's uncle

In my experience, I would bet on epilepsy being polygenic and in practical terms behaving as a dominant with incomplete penetrance.

Anyone that has witnessed an EIC collapse and an epileptic seizure, of whatever variety, would not mistake one for the other. However the explanation of the physical characteristics of either (or for that matter heat stroke) as related to a vet by an anxious owner (after the dog in question has returned to normal) may lead to a confused and/or mistaken diagnosis.

Sylvia

[Lablover]

To my understanding, there are is test for epilepsy. It is idiopathic.

To my knowledge, there is no test for epilepsy in ANY breed, least of all Labradors. The above quote is contradictory.

"Idiopathic" - adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. (Wiki)

If the cause is spontaneous or unknown, how can there be a test for it? I am aware of research on tests for epilepsy, however I don't believe there has been any breakthrough yet, particularly in Labs.

Linked atypical epilepsy, in labradors is presumed to be an autosomal recessive...thus possibly "more" difficult to follow on pedigree analysis without full disclosure/open data bases.

As EIC has the same mode of inheritance, (as does PRA), may researchers and scientists develop further DNA tests.

If epilepsy is autosomal recessive in Labs, then I'm a monkey's uncle :D

In my experience, I would bet on epilepsy being polygenic and in practical terms behaving as a dominant with incomplete penetrance.

Anyone that has witnessed an EIC collapse and an epileptic seizure, of whatever variety, would not mistake one for the other. However the explanation of the physical characteristics of either (or for that matter heat stroke) as related to a vet by an anxious owner (after the dog in question has returned to normal) may lead to a confused and/or mistaken diagnosis.

Sylvia

Stop it Sylvia!!!! You had me checking pedigrees again!! Reminds me yet again of our old friend MC.

[Lablover]

To my understanding, there are is test for epilepsy. It is idiopathic.

To my knowledge, there is no test for epilepsy in ANY breed, least of all Labradors. The above quote is contradictory.

"Idiopathic" - adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. (Wiki)

If the cause is spontaneous or unknown, how can there be a test for it? I am aware of research on tests for epilepsy, however I don't believe there has been any breakthrough yet, particularly in Labs.

Linked atypical epilepsy, in labradors is presumed to be an autosomal recessive...thus possibly "more" difficult to follow on pedigree analysis without full disclosure/open data bases.

As EIC has the same mode of inheritance, (as does PRA), may researchers and scientists develop further DNA tests.

If epilepsy is autosomal recessive in Labs, then I'm a monkey's uncle :nahnah:

In my experience, I would bet on epilepsy being polygenic and in practical terms behaving as a dominant with incomplete penetrance.

Anyone that has witnessed an EIC collapse and an epileptic seizure, of whatever variety, would not mistake one for the other. However the explanation of the physical characteristics of either (or for that matter heat stroke) as related to a vet by an anxious owner (after the dog in question has returned to normal) may lead to a confused and/or mistaken diagnosis.

Sylvia

Stop it Sylvia!!!! You had me checking pedigrees again!! Reminds me yet again of our old friend MC.

Wow!!!!!!!

http://www.pnas.org/content/106/33/14085.a...24-f1561bcfabfb

Mutation I810N in the α3 isoform of Na+,K+-ATPase causes impairments in the sodium pump and hyperexcitability in the CNS

Steven J. Clapcotea,b,1, Steven Duffya, Gang Xiea, Greer Kirshenbauma,c, Allison R. Becharda, Vivien Rodacker Schackd, Janne Petersend, Laleh Sinaia,c, Bechara J. Saaba,c, Jason P. Lerche, Berge A. Minassianc,e, Cameron A. Ackerleye, John G. Sledc,e, Miguel A. Cortezc,e, Jeffrey T. Hendersonc, Bente Vilsend and John C. Rodera,c

+ Author Affiliations

aSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5;

bInstitute of Membrane and Systems Biology, University of Leeds, Leeds LS2 9JT, United Kingdom;

cDepartments of Medical Biophysics, Medical Genetics, Paediatrics, and Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada M5S 1A1;

dDepartment of Physiology and Biophysics, Centre for Membrane Pumps in Cells and Disease–PUMPKIN, Danish National Research Foundation, University of Aarhus, DK-8000 Aarhus, Denmark; and

eMouse Imaging Centre, Program in Genetics and Genome Biology, and Divisions of Neurology and Pathology, Hospital for Sick Children, Toronto, ON, Canada M5G 1X8

Abstract

In a mouse mutagenesis screen, we isolated a mutant, Myshkin (Myk), with autosomal dominant complex partial and secondarily generalized seizures, a greatly reduced threshold for hippocampal seizures in vitro, posttetanic hyperexcitability of the CA3-CA1 hippocampal pathway, and neuronal degeneration in the hippocampus. Positional cloning and functional analysis revealed that Myk/+ mice carry a mutation (I810N) which renders the normally expressed Na+,K+-ATPase α3 isoform inactive. Total Na+,K+-ATPase activity was reduced by 42% in Myk/+ brain. The epilepsy in Myk/+ mice and in vitro hyperexcitability could be prevented by delivery of additional copies of wild-type Na+,K+-ATPase α3 by transgenesis, which also rescued Na+,K+-ATPase activity. Our findings reveal the functional significance of the Na+,K+-ATPase α3 isoform in the control of epileptiform activity and seizure behavior.

[sandgrubber]

To my understanding, there are is test for epilepsy. It is idiopathic.

To my knowledge, there is no test for epilepsy in ANY breed, least of all Labradors. The above quote is contradictory.

The above isn't contradictory, it's nonsense and clearly a typo. 'There is are test'. ??? There is work in progress on K9 epilepsy.

Here's a less technical article . . . that has been posted before on DOL

http://www.bsdaofgb.co.uk/idiopathic_epilepsy.htm

a paragraph from the above

Towards a DNA test for carriers of epilepsy in the Tervueren

Progress from now on should be quite rapid. Anita Oberbauer at Davis, University of California has now been awarded a new grant from the Canine Health Foundation to develop genetic markers for idiopathic epilepsy in the Tervueren. What does this actually mean? Although we know this major gene now exists, we don't know what it is, neither do we know where it is on one of those 38 different autosomes. Using the newly developed genetic map of the dog, Anita Oberbauer hopes to be able to localise the gene to one small region of one of those chromosomes. The genetic map of the dog is made up of a series of special DNA markers, each marker uniquely identifying just one region of one of the chromosomes. The map contains 100s of different markers ensuring that each chromosome is evenly decorated with DNA markers. What Oberbauer is trying to find out is which of these markers is always co-inherited with the mutant version of the gene. DNA regions that are always co-inherited are physically close to one another on a chromosome. Markers that are co-inherited with the mutant version of the gene are said to be linked to the gene.

The identification of markers linked to the mutant gene will immediately locate the mutant gene to one small region of one of those 38 chromosomes

[zenchel]

Wow!!!!!!!

http://www.pnas.org/content/106/33/14085.a...24-f1561bcfabfb

Mutation I810N in the α3 isoform of Na+,K+-ATPase causes impairments in the sodium pump and hyperexcitability in the CNS

Steven J. Clapcotea,b,1, Steven Duffya, Gang Xiea, Greer Kirshenbauma,c, Allison R. Becharda, Vivien Rodacker Schackd, Janne Petersend, Laleh Sinaia,c, Bechara J. Saaba,c, Jason P. Lerche, Berge A. Minassianc,e, Cameron A. Ackerleye, John G. Sledc,e, Miguel A. Cortezc,e, Jeffrey T. Hendersonc, Bente Vilsend and John C. Rodera,c

+ Author Affiliations

aSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5;

bInstitute of Membrane and Systems Biology, University of Leeds, Leeds LS2 9JT, United Kingdom;

cDepartments of Medical Biophysics, Medical Genetics, Paediatrics, and Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada M5S 1A1;

dDepartment of Physiology and Biophysics, Centre for Membrane Pumps in Cells and Disease–PUMPKIN, Danish National Research Foundation, University of Aarhus, DK-8000 Aarhus, Denmark; and

eMouse Imaging Centre, Program in Genetics and Genome Biology, and Divisions of Neurology and Pathology, Hospital for Sick Children, Toronto, ON, Canada M5G 1X8

Abstract

In a mouse mutagenesis screen, we isolated a mutant, Myshkin (Myk), with autosomal dominant complex partial and secondarily generalized seizures, a greatly reduced threshold for hippocampal seizures in vitro, posttetanic hyperexcitability of the CA3-CA1 hippocampal pathway, and neuronal degeneration in the hippocampus. Positional cloning and functional analysis revealed that Myk/+ mice carry a mutation (I810N) which renders the normally expressed Na+,K+-ATPase α3 isoform inactive. Total Na+,K+-ATPase activity was reduced by 42% in Myk/+ brain. The epilepsy in Myk/+ mice and in vitro hyperexcitability could be prevented by delivery of additional copies of wild-type Na+,K+-ATPase α3 by transgenesis, which also rescued Na+,K+-ATPase activity. Our findings reveal the functional significance of the Na+,K+-ATPase α3 isoform in the control of epileptiform activity and seizure behavior.

Yeah - what they said

[zenchel]

but at this point in time I think it is all a bunch of cobblers, and just another test for someone to make money on. I don't know about other Labrador breeders whom have had Labradors for years and years, but I don't see a rash of collapsing everywhere and didn't years ago either, Interesting that Master Mariner was a Carrier, I have Master Mariner in all my pedigrees and as yet not problems or they have been tested clear, does anyone really know the mode in inheritence.

Just thought I'd let everybody know that tonight I heard the tragic news from a Lab breeder friend that their dog died whilst in an EIC episode. Up until now I've been fairly sceptical of the reports of EIC leading to death, however this news has come as a real wake up call.

Sylvia

[sandgrubber]

Have attempted to move the epilepsy sub thread to a new thread . . .

Sorry to hear EIC fatality confirmed. It is a bit of a wake-up. Was it a US dog?

Edited February 5, 2010 by sandgrubber

[dancinbcs]

Hi all. I know this may have been covered before but just interested in some info re EIC testing, inheritance and anything related anyone may have to say re Labradors. I live in NSW and have 8 Labs of various ages. I have hear there are already restrictions in some states re breeding carriers? Any info would be appreciated.

No matter what breed or what condition you are talking about, if it is autosomal recessive, then CARRIERS SHOULD NOT BE ELIMATED from the gene pool.

Once a DNA test becomes available breeders have the power to completely avoid breeding stock affected by that conditon by simply always making sure that one parent is DNA normal for that condition. Carriers are not affected in any way and it doesn't matter if you have carriers in the gene pool for another 50 generations, so long as no affected puppies are being born. The majority of puppies go to pet homes and are desexed and it doesn't matter if they are carriers or not, so they don't even need to be tested. Affected dogs can still be safely bred to normals and will produce all carriers. So long as all breeding stock with a carrier parent is tested, and all carriers are then bred to normals the condition is no longer a breed problem it is a controlled condition.

Avoiding carriers when they are a substantial percentage of the breed, does untold damage to the gene pool, concentrating other undesirable mutations in the gene pool that is left. Most of these won't have DNA tests available so you will find that you are breeding more and more problems.

If a test is available for your breed, then please use it to ensure you are not breeding affected dogs, but don't stop breeding from carriers.

DNA tests were never meant to be used to eliminate carriers of autosomal recessive conditons. They were meant to open up the gene pool by enabling carriers to be safely used in a breeding program.

We need to get this message out to all dog breeders, no matter what breed or DNA test we are talking about.

BTW, I don't think epilepsy is inherited as an autosomal condition in any species. It is a very complex condition.

Edited February 5, 2010 by dancinbcs

[zenchel]

Sorry to hear EIC fatality confirmed. It is a bit of a wake-up. Was it a US dog?

No - UK show lines.