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MDR1 - can we eradicate?

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Any update or possibility the website will be update with a breeding recommendation? In looking, only those with no DNA test, except epilepsy, have a recommendation. It's been 10 months now and there are far more, far more, puppies produced from this dog. Quite a few puppy owners were not even made aware of the affected status wrt MDR1 and him, much less TNS. Yes, it's up to honest breeders, but let's face it...many are using him based on his European win. I think it would be nice if the ABCA/HEF at least made a recommendation. And let's not forget a newly raised concern, flea and tick products..

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Perhaps you should read the text on mdr1 on the website.

the only remaining change that should be made for accuracy is the first note under the table should read:

  • Estimated incidence rates are for dogs homozygous for the mutation, rates of dogs heterozygous for the mutation will be higher

 

There is no genetic test available to determine if a heterozygot will be more sensitive to these drugs than a homozygous normal.

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Unless it was changed today, reading it yesterday still had no breeding recommendation. If that's updated now, thank you!

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On 10/29/2018 at 2:41 PM, Mark Billadeau said:

There is no breeding recommendation and will not likely be one soon.  Our volunteered time is currently consumed by EAOD.

If you're asking for volunteers, I'd be happy to help!

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Don't buy a puppy unless both parents are Normal/Normal.

Neuter all carrying mutant genes.

Virtually no problem has a simpler solution.  Not that it is easy -- people are great at denial.

I lost a sheltie once to the Mdr1 mutation -- and an overzealous vet who used ear mite medicine without asking.

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54 minutes ago, MVAF said:

Don't buy a puppy unless both parents are Normal/Normal.

Neuter all carrying mutant genes.

Virtually no problem has a simpler solution.  Not that it is easy -- people are great at denial.

I lost a sheltie once to the Mdr1 mutation -- and an overzealous vet who used ear mite medicine without asking.

I'm sorry MVAF for your loss.

I absolutely agree with you, however, we can't do that as it would be detrimental the gene pool...

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19 hours ago, Journey said:

I'm sorry MVAF for your loss.

I absolutely agree with you, however, we can't do that as it would be detrimental the gene pool...

How is 0.5% detrimental to the gene pool?

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If the 0.5% carries the best working genetics. ABCA (and also ISDS, I think) are working hard to find ways to reduce the risk of creating dogs with these genetic problems without also diminishing the main reason the breed exists, which is its working ability. In the (Lassie) collie world, eliminating the mdr1 mutation is more straightforward because any working ability that breed had largely already been lost, so no worries about losing those complex genetics while trying to remove a mutation from the gene pool.

 

J.

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True that. But MDR1 is likely the tip of the iceberg. If we start there and continue trying to eliminate, could have serious consequences.

 

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Assuming Hardy-Weinberg equilibrium for all genetic diseases with tests in our breed (CEA, TNS, IGS, NCL, MDR1) and published breed frequencies are accurate

we desire to eradicate all these diseases by not breeding m/n or m/m dogs (“carrier” and “affected”)

no dog has more than 1 of these diseases

we would be excluding 49% of the population

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On 11/2/2018 at 10:20 AM, PaleRanger said:

How is 0.5% detrimental to the gene pool?

The problem is that this is not the only genetic defect or disease that can occur in the breed.  All dogs -- even all of us humans -- have defective mutations in our genes.  Usually you will never find out about it, because if the mode of inheritance is recessive (which it is in most cases), that gene will not meet up with a matching gene to create defective offspring.  The more diverse your gene pool and the less you inbreed, the less likely it is that they will meet up.  If the mode of inheritance is dominant, you will always find out about it, because the offspring will always display the defect so you won't want to repeat the breeding because you won't want to produce defective offspring.  

If you try to eliminate all of these defective genes once they do pop up, you definitely WILL harm the gene pool -- not just because you'll lose sources of valuable working genes, but because you'll eliminate the sources of other healthy genes.  It is vital for the health of any breed to preserve genetic diversity.  In a totally different context, it's kinda like "They came for the CEA mutation carriers and I thought that was a good idea.  Then they came for the IGS mutation carriers and I thought that was a good idea.  Then they came for the MDR1 mutation carriers, and I thought that was a good idea. . . .  Then when XYZ was discovered, we didn't have enough healthy dogs with diverse genetics left to keep the breed going."

So how do we deal with that problem?  We have to prioritize.  How prevalent is this particular mutation in the breed?  How serious is the disease it produces?  Are there any better ways to combat it than to eliminate all carriers from the gene pool?

In the case of MDR-1, we don't know how prevalent the mutation is, but all indications are that it is very infrequent in the breed.  That fact could make it possible at least in theory to eliminate it, but we would be removing valuable genes from the gene pool as well.  We do know that the defect it creates is one that will rarely cause harm -- only when certain drugs are administered to homozygote (and in some cases, heterozygote) dogs.  Would it make more sense to test all dogs before breeding and not breed carriers, or would it make more sense to test dogs before administering those drugs, and find an alternative to administer to those few who carry the MDR1 mutation?  Population geneticists would probably advise the latter approach.

 

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I must say, I find it very concerning that the powers that be are more concerned about a high profile dog being taken out of the gene pool, then with trying to control if not eradicate a fairly serious genetic defect, a defect that I don't think we even know what all it could impact.                                                                                                                                                                                     You all are concerned about the gene pool,  you don't want to diminish that gene pool of working dogs, fair enough.  Let's look at the dog in question shall we? What is so outstanding about this dog? Why is it so important that we continue to breed to this dog.  The dog in question came from the UK, from a very well known handler, the dog was the European nursery champion, in 2015 I believe.  He won a handful of other nursery trials in the UK as well, but that's about it, that is it! Nothing else on his resume.   Being a nursery champion really doesn't mean much, how many of you can recall who the nursery champion was (in the US) in 2015? hell who was it this year? So let's move on, the dog gets sold, comes to the US, to Texas, he has some success with his novice owner, in all fairness when the sheep are right, this dog is aces, but if they aren't, he is sunk, if the sheep are the least bit heavy you can forget it.  Just this past spring,  he was run at the Bluegrass, could not lift the sheep, a friend of mine ran him, and was mortified. And this isn't just a one of,  this happens here in Texas too, the dog can't lift the sheep or can't move them on a drive.  My friend who has a son of, has the same problem, if the sheep are right he's golden, but if not he ends up walking up the field to get his dog.  And let me tell you, that is heartbreaking, my friend loves this dog, and it kills him when this happens.  And we're not just talking about trial dogs here,  I can't see where these dogs would be much use as ranch/farm dogs either, they just don't have what it takes. And there is a third thing that some of you may not know, these dogs (this line) are known for being very quirky, freaky :-O  a lot have socialization problems, they are just very weird dogs.  So I suggest we look at the big picture here, before we're so quick to poo poo the MDR1 issue in defense of some mythical champion sheepdog...oh, and don't take my word for any of this, do the research yourself...pretty easy to pull up the scores etc. of this dog and of some of his get...

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My information may be completely wrong, however, I heard he was going back to the UK, TG. If that's the case I would hope that the ABCA shares their knowledge of the MDR1 with the ISDS (and the TNS). 

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2 hours ago, Little Bo Boop said:

I must say, I find it very concerning that the powers that be are more concerned about a high profile dog being taken out of the gene pool, then with trying to control if not eradicate a fairly serious genetic defect, a defect that I don't think we even know what all it could impact.

 

I'm sorry you have come to this conclusion, because it is an erroneous one.

2 hours ago, Little Bo Boop said:

                                                                                                                                                                                 You all are concerned about the gene pool,  you don't want to diminish that gene pool of working dogs, fair enough.  Let's look at the dog in question shall we? What is so outstanding about this dog? Why is it so important that we continue to breed to this dog.  The dog in question came from the UK, from a very well known handler, the dog was the European nursery champion, in 2015 I believe.  He won a handful of other nursery trials in the UK as well, but that's about it, that is it! Nothing else on his resume.   Being a nursery champion really doesn't mean much, how many of you can recall who the nursery champion was (in the US) in 2015? hell who was it this year? So let's move on, the dog gets sold, comes to the US, to Texas, he has some success with his novice owner, in all fairness when the sheep are right, this dog is aces, but if they aren't, he is sunk, if the sheep are the least bit heavy you can forget it.  Just this past spring,  he was run at the Bluegrass, could not lift the sheep, a friend of mine ran him, and was mortified. And this isn't just a one of,  this happens here in Texas too, the dog can't lift the sheep or can't move them on a drive.  My friend who has a son of, has the same problem, if the sheep are right he's golden, but if not he ends up walking up the field to get his dog.  And let me tell you, that is heartbreaking, my friend loves this dog, and it kills him when this happens.  And we're not just talking about trial dogs here,  I can't see where these dogs would be much use as ranch/farm dogs either, they just don't have what it takes. And there is a third thing that some of you may not know, these dogs (this line) are known for being very quirky, freaky :-O  a lot have socialization problems, they are just very weird dogs.  

You are making quite a good case that these pups are unlikely to be bred and pass on whatever genes they might have.  In fact, I question why anyone would be bringing bitches to this sire.  

2 hours ago, Little Bo Boop said:

So I suggest we look at the big picture here, before we're so quick to poo poo the MDR1 issue in defense of some mythical champion sheepdog...oh, and don't take my word for any of this, do the research yourself...pretty easy to pull up the scores etc. of this dog and of some of his get...

We are not doing anything to defend a champion sheepdog, mythical or otherwise.  We are still considering this whole issue in hopes of getting enough information to come up with the best solution.  I know that Denise Wall has reached out to some people to learn more about the case, but has so far not received any response.  We have no solid information about this particular dog -- only gossip so far.

But since you feel you have enough information to decide what should be done here, what is your recommendation?

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1 hour ago, Eileen Stein said:

I know that Denise Wall has reached out to some people to learn more about the case, but has so far not received any response.  We have no solid information about this particular dog -- only gossip so far.

I have not heard from Denise, nor has Eileen, who is running Peat my MDR1 affected pup. None of this wrt MDR1 or TNS is gossip when discussing Tanhill Glenn. I've spoken to UK breeders, have it in writing, their bitch was tested, entire panel, normal, pups came back MDR1/TNS. They spoke to the then owner, who knew this prior to sending him here. 

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16 minutes ago, Journey said:

I have not heard from Denise, nor has Eileen, who is running Peat my MDR1 affected pup. None of this wrt MDR1 or TNS is gossip when discussing Tanhill Glenn. I've spoken to UK breeders, have it in writing, their bitch was tested, entire panel, normal, pups came back MDR1/TNS. They spoke to the then owner, who knew this prior to sending him here. 

You were not one of the persons I was referring to that Denise has contacted. I don't know who Eileen is, but I'm pretty sure she too is not one of the persons Denise has tried to contact.  I believe Little Bo Boop is one, however. 

The information you mention re test results in the UK is third-hand to me, but if it is correct, those UK breeders can surely pass it on to the ISDS with more credibility than ABCA -- which has never seen these test results -- could do.

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3 minutes ago, Eileen Stein said:

The information you mention re test results in the UK is third-hand to me, but if it is correct, those UK breeders can surely pass it on to the ISDS with more credibility than ABCA -- which has never seen these test results -- could do.

Actually, I sent you the link, in one of the emails, showing the sire/dam and litter results. I'd think coming from one registration org to another would carry a bit more weight, after all, it affects the breed not just a particular litter. Maybe Boop can see if the test results can be emailed to the HEF on TG. They do exist. If not, I'll ask him if he would.

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1 hour ago, Eileen Stein said:
1 hour ago, Journey said:

You were not one of the persons I was referring to that Denise has contacted. I don't know who Eileen is, but I'm pretty sure she too is not one of the persons Denise has tried to contact.  I believe Little Bo Boop is one, however. 

Odd, we don't have test results on Hogan yet...we do on mine and the litter sire. And I have results on the dams sire and dam..

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On 5/7/2018 at 5:26 PM, Mark Billadeau said:

So lets just cut to the heart of it all.

 

Do you want to ban the breeding of a national or international champion if it is mdr1m/n?

Eileen Stein, this is what concerns me...the attitude, "omg!! he's an national.international champion!!! he may have a genetic mutation, but he's an international champion!!  and to be quite honest, I don't know Mark Billadeau, but I find him to be very condescending...                                                                                                                                                                                                        "You are making quite a good case that these pups are unlikely to be bred and pass on whatever genes they might have.  In fact, I question why anyone would be bringing bitches to this sire. "  Good question!!! Personally, I saw him in an arena trial, thought he looked pretty good, owner said thanks!!! he was the European nursery champion! LOL just so happened a litter came up when I was looking for a pup...I had no idea about the genetic issues or the weakness issues at the time. I don't know about you and where you are, but it seems like it doesnt't take much to have a flavor of the month dog...happens in Texas all the time,  I was at a trial in OK a few weeks ago, there were at least, at least! 20 dogs right within throwing distance that were all related...mine included.... The big thing now seems to be getting import dogs....HSweep seems to be the popular one now (of which I have a granddaughter of) I know a couple of folks have gotten pups by TG that were bred to cattle dog lines, (trying to beef up the power)  they are still young, but so far they are liking what they see.  One particular handler, someone you would know, has a pup that they quite like, however, 2 other pups in the litter have health issues, poor doers, liver problems...                                                                                                                                                                                                                                                           

Yes, Denise did reach out to me, and I thank her for that. If you read my previous post, I said straight up, I wasn't going to make a crusade out of this. Karen Rabbit and I actually split the sheets over this issue, I thought she had gone totally overboard on this subject, but then I started to have problems with my pup, and then got to thinking about a pup that died (from the same litter) and got to thinking, maybe there is something to what she was saying.  I don't pretend to know all the answers 

"But since you feel you have enough information to decide what should be done here, what is your recommendation?"   and no where did I say that.  I was totally up front, I'm not a scientist, doc, I don't do math...but I've been around a while, I have common sense, and when ever one of my dogs or a family member, gets sick, I start to research...I think there is enough going on here for the powers that be, to at the very least alert the membership about MDR1, that you don't know the complete story on it, that it is a fluid situation, and to use caution when getting a pup. I also wouldn't be opposed to seeing a page or some place you could go to record any issues you are having with one of these pups...I fully admit, MDR1 was not on my radar, was not a concern, thought it was much ado about nothing, but now...not so sure, and for me, I would not buy a dog that came from an MDR1 carrier, and  I will urge anyone I know to do the same. 

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My attitude/ire is brought out by the suggestion of a eugenics program with a limited view of the problem.  We’re not dealing with just one genetic disease; there are several we know about and many more that will be identified in the future.  This study surveyed 152 known diseases in dogs; many that are not tested for in our breed because we don’t recognize a high enough rate of the disease phenotype.  But that does not mean there are no heterozygotes (i.e. carriers) in our breed.

https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007361

 We must stop looking at this one disease at a time (one dog at a time) or each disease as a separate problem.  What we need is to focus on the entire gene pool/genome.  We need to be breeding for genetic diversity not breeding to exclude every genetic disease for which there is a test.  This is not a new idea; it’s not even the first time or the first thread where I’ve presented it.  It’s not my idea.  It has been promoted many times by others.  Here is one of those times from 2016.

https://www.instituteofcaninebiology.org/blog/three-key-strategies-to-reduce-genetic-disorders-in-dogs

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2 hours ago, Little Bo Boop said:

Eileen Stein, this is what concerns me...the attitude, "omg!! he's an national.international champion!!! he may have a genetic mutation, but he's an international champion!!  and to be quite honest, I don't know Mark Billadeau, but I find him to be very condescending... 

Just to be clear, when Mark wrote "Do you want to ban the breeding of a national or international champion if it is mdr1m/n?" he was not referring to the particular dog you have spoken of (who is not a national or international champion).  He was asking if a dog of undeniably superior working ability should be removed from the gene pool because he has a mutation that causes sensitivity to certain drugs.  I think that's a fair question.  I do see an inclination on the part of many people to get more upset about a problem you can test for, whatever it might be, than the overall level of working ability in the gene pool, which is more amorphous and harder to reduce to a number or a yes/no.  I think it's a natural human tendency, but one we should resist.

2 hours ago, Little Bo Boop said:

"But since you feel you have enough information to decide what should be done here, what is your recommendation?"   and no where did I say that.  I was totally up front, I'm not a scientist, doc, I don't do math...but I've been around a while, I have common sense, and when ever one of my dogs or a family member, gets sick, I start to research...I think there is enough going on here for the powers that be, to at the very least alert the membership about MDR1, that you don't know the complete story on it, that it is a fluid situation, and to use caution when getting a pup. I also wouldn't be opposed to seeing a page or some place you could go to record any issues you are having with one of these pups...I fully admit, MDR1 was not on my radar, was not a concern, thought it was much ado about nothing, but now...not so sure, and for me, I would not buy a dog that came from an MDR1 carrier, and  I will urge anyone I know to do the same. 

I wasn't being snarky or trying to suggest that you lack scientific qualifications when I asked what you'd recommend -- I genuinely wanted to know.  Do you want more regulation of breeding on the part of the registry -- saying who owners/breeders can breed to and who they can't?  That level of regulation, which is found in many countries, is not one that I think most people would find acceptable here in the US.  Do you think the ABCA should expel members for breeding dogs with certain mutations, and if so, what mutations would those be?  Do you think the ABCA should require genetic tests for registration, and deny registration to dogs who test positive for certain mutations?  There are a number of reasons that we don't do that, and I think they're good reasons.

Now it is sounding more as if you favor an educational approach, and with that I agree.  We have tried to do that with the ABCA Code of Ethics and Best Practices and  in the Genetic Diseases section on the HEF website.  The MDR1 (ABCB1) entry there is not perfect, and we are trying to investigate further and expect that it will be improved over time.  We have also discussed developing a separate article for the Health and Genetics section that would discuss inheritance patterns that are less widely known than simple dominant and recessive, which we could link to from the MDR1 entry.  I expect we will probably do this when time permits.  I doubt we will have a page where you could go to record any issues you are having with a pup, but others have done that with regard to other heritable diseases.  I think that discussions with friends and acquaintances about the problem as you've encountered it, and recommending against buying a dog from an MDR1 carrier is a legitimate and effective way to advance your point of view.  I think that kind of "consumer pressure" has resulted in a greater acceptance of genetic testing than existed when I first got into this -- it has probably had at least as much effect in changing attitudes as the continuing and significant efforts of the ABCA.   

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9 hours ago, Eileen Stein said:

Just to be clear, when Mark wrote "Do you want to ban the breeding of a national or international champion if it is mdr1m/n?" he was not referring to the particular dog you have spoken of (who is not a national or international champion).  He was asking if a dog of undeniably superior working ability should be removed from the gene pool because he has a mutation that causes sensitivity to certain drugs.  I think that's a fair question.  I do see an inclination on the part of many people to get more upset about a problem you can test for, whatever it might be, than the overall level of working ability in the gene pool, which is more amorphous and harder to reduce to a number or a yes/no.  I think it's a natural human tendency, but one we should resist.

If you followed the thread, it was clear that Mark was referring to the the dog I was referencing,  TG was the dog in question pretty much throughout the entire thread, and TG is an international champion, by way of winning the European nursery championship.  As you said, I'm not being snarky, but do you know what dog we are talking about here?  

 

 

9 hours ago, Eileen Stein said:

I wasn't being snarky or trying to suggest that you lack scientific qualifications when I asked what you'd recommend -- I genuinely wanted to know.  Do you want more regulation of breeding on the part of the registry -- saying who owners/breeders can breed to and who they can't?  That level of regulation, which is found in many countries, is not one that I think most people would find acceptable here in the US.  Do you think the ABCA should expel members for breeding dogs with certain mutations, and if so, what mutations would those be?  Do you think the ABCA should require genetic tests for registration, and deny registration to dogs who test positive for certain mutations?  There are a number of reasons that we don't do that, and I think they're good reasons.

I appreciate that, and I was not/never suggesting that we ban or regulate the breeding of dogs, if you read my earlier posts, I stated and I understand the ABCA is quite limited in what they can do,  I totally understand that they don't have the power to compel an owner to neuter or cease breeding their dog, I get that!! and I'm all for that.  I don't want anyone's rights being taken away.  Having said that,  knowledge is power, as an example,  the ABCA took a reasonable stand on high volume breeders,  they posted them on a list, for everyone to see, they didn't take away their breeding rights, they didn't call them out personally, didn't disparage their dogs or breeding programs,  they just let the folks know that these people were pumping out a lot of puppies,  it's up to the buyers to do their due diligence, and decide if they want to purchase a dog from someone who cranks out a ton of dogs every year. 

Now it is sounding more as if you favor an educational approach, and with that I agree.  We have tried to do that with the ABCA Code of Ethics and Best Practices and  in the Genetic Diseases section on the HEF website.  The MDR1 (ABCB1) entry there is not perfect, and we are trying to investigate further and expect that it will be improved over time.  We have also discussed developing a separate article for the Health and Genetics section that would discuss inheritance patterns that are less widely known than simple dominant and recessive, which we could link to from the MDR1 entry.  I expect we will probably do this when time permits.  I doubt we will have a page where you could go to record any issues you are having with a pup, but others have done that with regard to other heritable diseases.  I think that discussions with friends and acquaintances about the problem as you've encountered it, and recommending against buying a dog from an MDR1 carrier is a legitimate and effective way to advance your point of view.  I think that kind of "consumer pressure" has resulted in a greater acceptance of genetic testing than existed when I first got into this -- it has probably had at least as much effect in changing attitudes as the continuing and significant efforts of the ABCA.     

I fully admit to you that before all this came up, I thought all this DNA testing had gone way overboard, I have BC friends who are rabid about testing,  they know every test, what they mean, all the tech. lingo LOL  I knew CEA and that was about it...When this MDR1 thing popped up, I immediately thought oh, Ivomec sensitivity, no biggie, I always assumed you couldn't give Ivomec to Border Collies, no big life changer for me...well as it turns out, it's not just Ivomec, it's a myriad of other things, and from what I've read the list is growing, and the full impact of MDR1 is really still unknown.  I think we need to be talking to the Aussie, Sheltie and Collie folks, see how they like having this mutation in their breed, and what kind of impact it has had on their dogs.  From what I gather, the incidence of MDR1 in the US pop. of Border Collies, is/was very low, I believe it's higher in the UK.  I'd be curious to see how many US dogs are MDR1 carriers. Also, keep in mind, this dog we are discussing, he was, at one time,  I believe the 3rd leading sire in the world, they have bred the hell out of this dog.                                  

As a Border Collie owner, and as someone who LOVES the breed, this is what I would like to see from the ABCA, our steward of the breed.  I would like, much like you did with the volume breeders list,  information on the genetic defects that affect our breed. Yes, I know, we can always google things like that, but there's always the 'you don't know, what you don't know' .  Give us a list of the issues, give us info. allow us to make informed decisions when purchasing a puppy. Had I known about this MDR1 stuff beforehand, I would not have purchased the pup I have now...and no way I would buy one in the future with that mutation.  And as an aside, had I come on here, and read what Mark B. had to say, I would have merrily bought the pup, MDR1?  not a problem!!   Let us know! and don't talk over peoples heads, we aren't all science types,  I don't know a heterozygote from a billy goat...explain things in terms we can understand, then we can make informed decisions.  And lastly I would ask that you (not you personally) don't abuse or dismiss people that ask questions or bring up topics that maybe weren't on your radar, or that maybe you just don't think matter.  Karen, might have been a bit abrasive in her approach, but she brought up a lot of good points,  points that are worth looking into in my estimation, she tried to bring something to the board that she thought important, it impacted her, she has a pup from this line, she has a dog in the fight... I didn't always feel that way, but now I guess I have a dog in the fight as well...        

Final word, I don't know the impact of MDR1 on our dogs,  it could be minimal could be nothing...but the thing is, we just don't know...I've seen enough to make me wonder, so if nothing else,  IMHO it should be monitored, hell it doesn't cost anything, so what's the harm?  

 

 

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