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LazarusMastiffs

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Reply with quote  #76 

Does anyone know why they are calling it cystinuria?  This is gonna sound gumby, but it is true.  It is just a combination of the two words meaning that there is cystine in the urine.  One thing it is not, is the same condition that they have in Newfoundlands.  The dog genome has been mapped and the marker for classic cystinuria(such as some newfs have), has been found.  To my understanding, it is simply not there in the mastiffs that have tested positive.  So let's all make certain not to read all the info on a different form of cystinuria found in another breed and try to transpose those findings on to how it affects our breed.   


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Reply with quote  #77 

So, I have a relatively easy question for everyone. Why would you NOT do the cystanuria test if it's the best test we have? The worst that can happen is a false negative when the dog is really C+. If it comes back positive, your dog is positive.


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LazarusMastiffs

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Reply with quote  #78 

Actually, the worst thing for a breeder would be a C+ when they are negative.  A C+ would implicate not only that dog, but both sides of the pedigree and their parents.  Their entire breeding program could be wrecked because the testing method is flawed.  Right now, they are telling most people that a + result is infallable, while at the same time, they are telling others that their diets and supplements may cause a + reading when it would normally wouldn't have.  You can't have it both ways, but they have been telling everyone for some time now that the former was correct.....  It is kinda hard to back off a line so clearly defined after you have drawn it....  I guess they can always stand behind the fact that any dog showing cystine in their urine does have cystine in their urine, so it fits the definition of the word cystinuria.  It does not however, necessarily mean the dog has a problem with anything.


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Reply with quote  #79 
Their entire breeding program could be wrecked because the testing method is flawed.  Right now, they are telling most
HI :>)
Yupper ,Chris its already happening
But thats the best we have

So what would you do ?? Stop breeding that line ? Or go on and take the chance to breed it anyway ??

Some are doing  just that ,Some say You can still show a C+ dog .
Or a postive Bitch ,But just dont breed them .

So why go through all the money ,on showing a Super Dog ,that cant be bred ?

Isnt that why we show ,the Champs are suppossed to be breeding material ?? And healthy ? Isnt that why we test in the first place ??

We cant show a Mastiff thats been spayed ,But wouldnt it be the same if we showed one with Cystinuria ?? Im sure hoping ,no one would breed to HIm
MArge



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Reply with quote  #80 

Sorry, but I suscribe to the theory there are no false positive. If my boy ever tested positive, I'd neuter him and never breed him. I feel very strongly about this since anyone I've ever know that had a stone former boy went through absolutely HELL trying to keep them comfortable. Personally, I would NOT want to have this on my conscience. It's NOT like there are too few quality Mastiffs around to keep the gene pool thriving. I'm not just saying this as an abstract thought. I just spayed a beautiful apricot girl that might have been a carrier of cystanuria since her mother threw several boys that ended up being C+ from a previous litter. Again, if I had bred her and she threw C+ boys, I would have felt like a complete jerk breeding her and selling her pups to others only to have them have affected boy. It's one thing to NOT know because the boys don't test until later in life, but when you have an idea you might have a problem and breed anyway, I don't see how this could not bother a breeder. This is one reason I have such a HUGE respect for breeders who are honest about the testing. It takes real guts and commitment to the breed to use the best tools possible to make sure we don't ruin this great breed. And yes, I know of one of the most awesome, ethical breeders I know who had to scrap a large part of her breeding program due to this issue BUT SHE DID IT because she has ethics and morals. If everyone was like her, we'd be light years ahead in this breed! 


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LazarusMastiffs

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Reply with quote  #81 

There is no need to apologize for any theory you have.  I have my own theories as well.  I believe some forms of cystinuria are inheritable.  I've seen too many cases in which it is traceable to feel otherwise.  Keep in mind that the example you gave, although noble, of sacrificing a girl you bought(or even someone else sacrificing some fo their own dogs)is not the same as asking a 70 year old woman/man to sacrifice the last 30-50 years of their life's ambition due to the readings of one, shaky at best, test.  Asking them to start over instead of trying to breed out of it, is not a subject I would approach in that scenario!  LOL  Keep in mind that I started over after several years with COMPLETELY different lines than I started with because of health issues as well.  Asking someone to potentially abandon everything they have done for longer than I am alive though.....  I would personally do more than I would expect of others.  That is kind of the way I was raised though.  I do not expect everyone to act in the same manner I would, nor do I try to judge others for their choices.  As long as people are open about it, it will not be spread to anything that could affect me or anyone concerned about it anyway.  BTW, C+ dogs and stone forming dogs are 2 differnt groups.  Kinda like all Baptists are Christian, but all Christians are not Baptist.....  Most c+ dogs do not form stones. 


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Reply with quote  #82 
as asking a 70 year old woman/man to sacrifice the last 30-50 years of their life's ambition due to the readings of one, shaky Chris :>)

Chris
Ya kinda hit a age thing here
I know of a Lady has a C+ Mastiff , Had dreams of showing and breeding Him .

But He came up with C+ and a stone former .
She and Her hubbie are in thier 60s ,It cost her 600$$$ for the meds a month .
He has now lost His job ,and thier , Health Insurance .She coooks for  Her dogs .
She now has two C+ Dogs ,The other is not a Stone former yet .

So i ask this to alll breeders ,that do breed C+ dogs .
How could you put this on someones back ?

You get 2,500 and up for your pups ,but how in the hell can you expect a buyer to pay  that bill ,to keep your Dog going ???

Im sure you would agree ,that no amout of ,type or pedigree is worth that ??

So then we come back to ,testing :>)  Or do you start guranteeing for Cystinuria ??

Since we cant really ,gurantee any genetics in any breeding .

We gurantee for Hips ?? why not cystinuria ?

If a breeder wants too breed a C+ He/She should be also ready to pay the piper .
Marge





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Reply with quote  #83 

Quote:

So do you think if we gave out Mastiffs ,that are positive put them on B12 pills or Gave them B12 shots , would help ?


As in taking  a C+ Mastiff giving B12 shots ,then take Him back in to have Him tested and see what the out come could be????

I also know of some breeders, that give their Mastiffs, Sammie to calm them down ,do you think that would also be a NO NO ??



Hi Marge, I think it would be a very interesting experiment to put C+ mastiffs on B12 and see what happens!

As far as the Sam-e, I guess if it were genetic homocystinuria causing a defect in synthesis of methionine it would be a no-no, but if it were nutritionally based it might actually be a good thing to supplement a diet lacking in methionine with Sam-e. 

The problem is, can anyone say with 100% assurance that what mastiffs are experiencing is indeed a genetic defect (homocystinuria or cystinuria), or nutritionally related (or even another genetic defect that causes intestinal malabsorption) ?
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kaysti

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Reply with quote  #84 
"There are various similar disorders that cause different phenotype besides excess cystine and other amino acids in the urinary tract such as excess cystine in the blood, the intestines, and even cystine crystals in the eye... As you obviously know, it is extremely time consuming studying all of this stuff because it can be very interesting if you're interested in such things and everything you look up leads to something else to look up..."


 
Anna, yes you are right, even the tiny little bit of internet research I did was extremely time consuming, and I'm sure it's only the tip of the iceburg. Every question leads to more questions!I'm glad to hear that UPenn has looked at the possibility of other genetic (possibly X-linked) diseases causing an elevation of cysteine.
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kaysti

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Reply with quote  #85 
Quote:
Originally Posted by Teresa

Excellent post! Most of the questions I cannot answer, but I do know that one of the upcoming test is to feed a "test diet" that SHOULD cause a C+ dog to test positive and maybe even force a female into excreting cysteine thus testing positive (which contrary to popular lore has NOT happened yet). I do not have the details yet, but when I hear, I'll be glad to share it.


Teresa, sounds very interesting... do you know if they will be using C- dogs as a control?  Maybe even using a different breed of dog in which excess cysteine is not even an issue?? 
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LazarusMastiffs

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Reply with quote  #86 
But He came up with C+ and a stone former .
She and Her hubbie are in thier 60s ,It cost her 600$$$ for the meds a month .
He has now lost His job ,and thier , Health Insurance .She coooks for  Her dogs .
She now has two C+ Dogs ,The other is not a Stone former yet .

So i ask this to alll breeders ,that do breed C+ dogs .
How could you put this on someones back ?

Was the breeder aware of the situation?  Was the owner informed of the risks?  Were the parents stone formers or C+?  If she is making the food for them, how can we be sure it is not the diet causing the problem?  There are a lot of questions that need to be asked before we rush to judgement on someone.  Not that you have, you may know the answers to all those and then some(knowing Marge she probably does).  But those are the types of questions we need to be asking when we see instances like this. 

     On a very serious note here, it is common practice among older individuals to feed eggs/raw eggs to dogs with their food as a supplement.  It used to be recommended by a lot of breeders to improve coat etc.  Eggs are VERY high in cystine and protein.  Is it possible that she is adding that to their food?  Not pointing fingers.  I do not know the people or dogs involved or if there is a history, but it would be good to know for a point of reference. 




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kaysti

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Reply with quote  #87 
Also, I don't know if I am comfortable with the term "false negative" when referring to cystinuria.

The Nitro Prusside test tells us whether the dog has cysteine (or homocysteine?) in the urine, or not... simple as that.

A negative result means there was no cysteine in the urine at that time. 

At this point, based on the current research Upenn is doing and also what I've read about the various disorders, I wouldn't feel comfortable assuming that a positive test for cysteine in the urine is definitely caused by the genetic disease referred to as cystinuria as we know it. (a mutation that affects the transporters in the kidney) or even homocystinuria (which is a mutation that affects the synthesis of methionine).

Again, unless someone can completely rule out all other possibilities for an elevated cysteine level, how can assume that one instance of elevated cysteine means the dog has genetic cystinuria?

Just trying to look at this as objectively and logically as possibly.
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LazarusMastiffs

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Reply with quote  #88 

On a side note.  An example of a situation that does nto sit well with me.  There was a breeding done by two dogs that I felt carried a lineage supporting cystinuria.  One side made it known and was clear about it.  The other side hid the fact, so the breeding was done in an effort to breed it out by one person(probably futile in this case)and the other specifically used the former to sell puppies while laying blame to the other side for any C+ puppies that may have resulted.  How shady is that?!!  True story and definately an example of poor ethics on one side anyway.  An unfortunate example of greed in the community.


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Reply with quote  #89 
First I want to say I am so glad this is all coming out - I had no idea how much we needed to learn on cystinuria and it's fascinating to be collecting all of this info from you guys!

Hypothetical example.... if you knew of a C+ dog forming stones and having major issues and both parents test negative. Would you suspect that the bitch is a carrier and passed it on to the son? Or is it possible the sire passed it on and is not having issues yet so tested negative. Then... would you ever get a puppy or grandpuppy out of that sire or avoid it b/c not sure where the C+ came from?

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Reply with quote  #90 

So many variables here. One line of thought is that the moms' are the carriers, but nothing absolutely concrete on that. Remember, girls don't test positive. Also, even C+ males don't necessarily test positive until they are older. Puppies that were tested came out fine as puppies, but when tested over several years, came up positive after 3 years. SOOO, the male could be the problem if he was tested too young. The general line of thinking is to test boys every year after 3 years old to attempt to catch it. That's how we found out there was a possibility of my girl that was spayed being a carrier. Her mom's first litter threw C+ boys but none of them tested positive until they were over 3 years old. My girl was out of a litter 2 years later prior to the positive boys coming up positive. Since it seems to involve some very complex genetics, I didn't want to risk adding to the problem so she was spayed. Would I have made the same decision if she were my foundation bitch and I'd invested many years developing the lines? Absolutely.


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LazarusMastiffs

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Reply with quote  #91 
Hypothetical example.... if you knew of a C+ dog forming stones and having major issues and both parents test negative. Would you suspect that the bitch is a carrier and passed it on to the son? Or is it possible the sire passed it on and is not having issues yet so tested negative. Then... would you ever get a puppy or grandpuppy out of that sire or avoid it b/c not sure where the C+ came from?

IF it is x-linked, which is my personal best guess for truly inheritable C+ dogs.  It would have to come from mom.  The majority of stone formers out there IMO have inheritable C+.  It can be passed on by dad, but only in his female offspring.  Since females never show a positive, I am going to assume this hypothetical stone former is a boy.  Males have one X and one Y to pass on.  Any offspring that get his x chromosome will be bitches since the mother only has two x's to pass on.  Therefore, dad always determines gender by either passing on his x(female) or his y(male) and cannot be responsible for a positive boy but can be for a positive girl.  With that said, this particular dog would have gotten it from his mother.  She could have gotten it from her mom or dad or both.  The sire could be a carrier as well, but since an affected male can only give a clear y or an infected x, he is irrelevant in this particular scenario.  Again, please remember that this is a hypothetical and depends on the cystinuria being a genetic form and it being x-linked.  Which is our best guess at this time.  Hope that helps. 

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Reply with quote  #92 
All X-linked traits will follow the same potential paths.  All traits in boys got it from mom.  All traits in girls could have came from mom, dad or both. 

Since we cannot test for cystinuria in girls, we have to wait and see if they produce any C+ boys before we can draw judgement on them(unless there is a history). 

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Reply with quote  #93 
Yup, that's the current line of thinking!

Now, just for sake of interest, I'd love to hear some ideas on the next scenerio. You have a bitch bred 3 times to all different males. Only one litter out of three test positive for C+ male pups. Any ideas how this can happen?

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Reply with quote  #94 

The female was the culprit in the male, if it is X-linked.  How many boys were there in the other 2 litters combined?  Each one would have as low as a 50% chance of carrying it.  Flip a quarter over and over.  It is surprising how many times one side will show up repeatedly.  It is only with large numbers that the 50% can be counted on as accurate.  This is not an uncommon occurrence with breeders.  Most likely due to the relatively small sample taken from and the likelihood of false negatives.  They should proceed cautiously if they plan on going ahead with any dogs from any of the breedings that bitch produced, her siblings etc. 


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Reply with quote  #95 
Thanks Chris and Teresa... my example is a boy - and that does make sense if it is X-linked - I hadn't thought of it that way. So, Chris, what you're saying with Teresa's example is that it was just luck of the draw? Purely chance that only one litter came up with positives?
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LazarusMastiffs

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Reply with quote  #96 

If it is x-linked, the easiest way to definatively eliminate the condition is to use males.  Keep a boy and breed it to an unaffected bitch from a proven line.  All his male offspring will be clear.  His females will still be a crapshoot, so be careful with them!!!  If you use a possibly affected bitch, it is very hard to trace. 


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LazarusMastiffs

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Reply with quote  #97 

Jen, I would not call it luck.  With the number of false negatives actually being higher than the number of positive results I have seen in affected dogs(when they are continually testing), I would call it typical. 


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Reply with quote  #98 
Was the breeder aware of the situation?  Was the owner informed of the risks?  Were the parents stone formers or C+?  If she is making the food for them, how can we be sure it is not the diet causing the problem?  There are a lot of questions that need to be asked before we rush to judgment on someone.  Not that you have, you may know the answers to all those and then some(knowing Marge she probably does).  But those are the types of questions we need to be asking when we see instances like this. 

Chris :>)
I'm not sure if that a compliment or not
Anyway , The owner cooked for the Dogs ,after She had found out they were C+ .

She is very up on all things concerning this Genetic nightmare :>)
No the One Breeder did not know anything about this Genetic defect .

But when she found out from the owner ,She still did not change her breeding practices . We also have to remember ,that many in other country's ,have no idea about this or about genetics periods

And I'm sure they just Phoo Phoo it anyway

I think they are working on it :>) and trying very hard to understand it

But look at us  here we sit trying to figure it out ,and we have no straight answers either ,so i guess  you cant blame anyone in another Country

Thinking we are crazy :>)

I do like seeing these post ,on Cystinuria come up .
From time to time ,it keeps us aware  and talking about it :>)

And sometimes we learn one more small thing on it .

Marge 

And sadly still don't know anymore than we did many years ago .

Sad thing now is ,it is getting to be a serious problem .
Chris !  hope to see you at Bucks :>)

Hugs Marge 

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Reply with quote  #99 

I guess I don’t know how to do the box thing when snipping parts of someone else’s e-mail on a message board, so I’m doing it the old fashion way of using >>> at the beginning and at the end of the comments I’m replying to.  I wish I could reply to more posts, but I can't keep up :-)

 

>>>Well based on that 'theory', breeders could just feed their pups a standard kibble all their lives..never give them abnormal amounts of protein and they will not test positive..no excess cystine in the urine, no cystinuria...no problem.>>>

 

The way I understand it, UPenn would like to verify if giving our dogs a diet high in protein and amino acids can influence Cystinuria phenotype in Mastiffs and some other breeds of dogs.  Although we already know some C+ dogs will test NP positive no matter what we feed them.  They would like to help us identify those C+ dogs & hopefully carrier bitches that normally would go undetected with the current NP Urine Screening test that they are currently using.

>>>So all these dogs are expected to be removed from the gene pool because they can metabolise normal levels of protein but cannot handle abnormal amounts of protein?>>>

 

I cannot speak for everyone and those opinions will be from one end of the spectrum to the other, but here in the United States the Mastiff Club of America's Health Committee and Cystinuria Sub-Committee “along with many MCOA members, non-members and other breed clubs” have a goal of supporting research that will lead to a DNA test for Cystinuria which will identify normal, carrier, and affected animals (depending on the actual mode of inheritance).  The DNA test can then be used to assist breeders when making our breeding decisions by helping us achieve our goals of selectively breeding for traits we desire and also assist us in trying to breed away from undesirable traits.

 

A lot of us also recommend and encourage breeders to make breeding decisions based on the individual dog or bitch’s temperament, breed type, and health status (based off of their known phenotype and genotype).  If a breeder has an otherwise exceptional dog that would add value to the gene pool, then they are blessed with the ability to freeze the dog’s semen for future consideration in their breeding program.  Unfortunately with known carrier bitches, these types of options are not currently economically available.


>>>geez..I'm over it...>>>

 

Are you willing to translate that comment for us?  I'm curious if that has the same meaning in New Zealand as it does in the United States in case some of us do not understand you correctly. 

 

Anna

 


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Reply with quote  #100 
snip...
>>>can Upenn do research on other possible diseases that might elevate cysteine or homocysteine levels, or does the Cystinuria grant limit the research to genetic Cystinuria only>>>

Right now UPenn's current Cystinuria Grant is looking at genetic Cystinuria since they are finding genetic statistical information through pedigree analysis and genome mapping technology on the Mastiffs that are participating in their research.  They could definitely use more participants by the way.

UPenn cannot run full quantative amino acid tests on every urine sample they receive, but they have been running them on the dogs that they are studying their DNA and they are looking at dogs with excess COLA which includes cystine.

If you know of enough dogs that have been diagnosed with elevated homocystein, hyperhomocysteinemia or cystinosis... and they would like to participate in a research study, they would have to be willing to finance the study or find financial backing for the study, share pedigree information, share environmental information such as diet and supplements, and submit DNA samples... 

I had asked UPenn about looking into this in Mastiffs since some lines actually could have an issue of traits similar to mental retardation and I was told they are looking at dogs with elevated cystine other amino acids in the urine not cystein and not elevated cystine in the blood or intestines or eyes and that would require a separate study.

http://www.med.uiuc.edu/hematology/PDF%20Files/Hyperhomocysteinemia.pdf

If on the other hand if the current research study shows a significant number of Mastiffs that do not show the same gene mutations and pedigree analysis data but have NP C+ results, then I'm pretty sure that could possibly lead to a new Grant or possibly a new recall on food &/or supplements.

Anna

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