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mariaruoto

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Reply with quote  #176 
This page is old so the cost of the test is outdated - but what is said is good:
Cystinuria in Scottish Deerhounds...
http://www.caberfeidh.com/Cystinuria.htm
http://www.deerhound.org/forms/clay_cystinuria_2.pdf

From PennGen (5/2008)...Note the part about the Newf stud that sired 100 offspring (goes back to the analogy in the first post)...
http://research.vet.upenn.edu/LinkClick.aspx?fileticket=ekWr0O4Rakc%3d&tabid=545&mid=960

 
Attached Files
pdf Cystinuria_(Urine_and_DNA).pdf (24.22 KB, 11 views)


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mastiffmom

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Reply with quote  #177 
I asked this question before but never really got an answer.

If you test your male at a year and he is negative, should you continue to test until you get a positive.  Now lets say when he is 6 yrs old he comes back positive, does that mean that he was positive all along, or does this mean that maybe his diet is a contributing factor to the positive.  Now that he is positive, does that mean it is a FALSE positive or a TRUE positive.

If this male has had all other health testing done and the owner has CHAMPIONED him out and feel he is worthy, should he not be bred until later in life even if for 5 yrs he has had negative results.  I guess I am not clear on how many times you should test your dog, and whether you should continue to test until he show positive.

I would really like for someone to answer this if possible,  To me it is a bit confusing.

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steveoifer

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Reply with quote  #178 
With present testing methods, one should repeat the testing even if negative.

The problem is when a test comes back negative and the champagne gets broken out!

If a dog turns positive at age 5 it can mean two things........

(i) He was positive all along and the testing was inaccurate.

(ii) Something has reduced his ability to absorb the cysteine over time and now presents as positive. This can be genetic, or biological in origin. Much like diabetes.
 
In either case, to be safe, both must be treated as genetic until better methods are developed in determining causality.



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For the betterment of the breed

"Above all, a uniform type should be aimed at by breeders and uniformity of type can only exist in a proportionate ratio in the purity and distinctiveness in any breed"!.........M. Moore
"If breeds did not adhere to a specific shape, form, and colour range, or if breeders disregarded this blueprint, the breed would degenerate to the point that it would hardly resemble the breed at all. Selective breeding does not just create breeds- it preserves them as well." Breeding purebred dogs inherently means accepting limitations on your freedom to just breed anything...Catherine McMillan
" A reinforced consolidation of the American and British standards could be the basis for restoring our breed to the gladiatorial glory of its ancient past, in capability if not in usage".....Norman Howard Carp-Gordon
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mastiffmom

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Reply with quote  #179 
thank you Steve for clearing this up.

Quote:
Originally Posted by steveoifer
With present testing methods, one should repeat the testing even if negative.

The problem is when a test comes back negative and the champagne gets broken out!

If a dog turns positive at age 5 it can mean two things........

(i) He was positive all along and the testing was inaccurate.

(ii) Something has reduced his ability to absorb the cysteine over time and now presents as positive. This can be genetic, or biological in origin. Much like diabetes.
 
In either case, to be safe, both must be treated as genetic until better methods are developed in determining causality.


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margelutz

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Reply with quote  #180 

From PennGen (5/2008)...Note the part about the Newf stud that sired 100 offspring (goes back to the analogy in the first post)...
 
Well Maria,
That was an eye opener for sure
 
Marge

 

 




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steveoifer

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Reply with quote  #181 

Just got off the phone with Urs Giger.

We discussed a number of issues regarding cyst in Mastiffs and in other breeds as well.

I asked if it was possible that it's polygenic, this would increase the difficulty in finding a specific locus. He said that it was possible, but he thinks it would only be 2 genes, but not in stone (no pun intended).

I asked the next direction they would take in research. I was told that the genome wide scan was the next direction, but it's expensive. 10,000-100,000 markers per dog would be looked at.

Double XX affected females and those that are carriers do not test positive.

They are looking at the Y chromosome now to see if that might carry a bit or fragment which would add to the problem.

Newf & Lab mutations were not of the same origin.

The one female that showed positive was an anomaly.

Positive affected males don't usually throw affected males.

Diet low in protein can mask positives.

Low PH is beneficial to affected dogs. Acidity increases stone formation.

Speculation that a gene transporter could be affected in older dogs, which may be the reason for the increase in positives as the dog ages.

Nutra Grass and Super 14 can skew results, hypothetical, but likely valid.

Basically, they are still up in the air in Mastiffs and a lot more research is needed to pinpoint the issue.

Breeders that are intentionally forcing better outcomes by special diet prior to testing, are just creating more issues for the breed.

No common denominators.

We spoke of the affects of fluoridation in water, from one study I read on cysteine, to Beagles & Deerhounds.

Then we both needed to break off the conversation, due to other issues, but stated that we would talk again.

Hope this gives everyone a better handle on the "state of the art"!



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For the betterment of the breed

"Above all, a uniform type should be aimed at by breeders and uniformity of type can only exist in a proportionate ratio in the purity and distinctiveness in any breed"!.........M. Moore
"If breeds did not adhere to a specific shape, form, and colour range, or if breeders disregarded this blueprint, the breed would degenerate to the point that it would hardly resemble the breed at all. Selective breeding does not just create breeds- it preserves them as well." Breeding purebred dogs inherently means accepting limitations on your freedom to just breed anything...Catherine McMillan
" A reinforced consolidation of the American and British standards could be the basis for restoring our breed to the gladiatorial glory of its ancient past, in capability if not in usage".....Norman Howard Carp-Gordon
"I can live with doubt, or not knowing, rather than to have answers that might be wrong"...Richard Feynman
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Teresa

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Reply with quote  #182 
Thanks Steve.
Just a few clarifications for those that don't understand pH. When Steve says lower pH, he means more basic which is actually higher on the pH scale. Water is roughly 7, highly basic is 14. A C+ dog needs to be higher than 7. Acidic is below 7.



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Crossroads

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Reply with quote  #183 
Quote:
Positive affected males don't usually throw affected males.


This one is interesting to me.  Early information stated about half the litter from a posistive affected male would be either a carrier or affected.  Does this mean that more focus should be put on carrier bitches? 


Quote:
Speculation that a gene transporter could be affected in older dogs, which may be the reason for the increase in positives as the dog ages.


Does this mean that until a dog tests positive it is safe to use him as part of a breeding program?  If a stud dog has received negative results every year until age 6 does that mean that every one of his offspring could be affected or is that particular stud dog not capable of passing it along until he tests positive????

Quote:
Double XX affected females and those that are carriers do not test positive.


Does this apply to Mastiffs?  I thought females could not be affected in this breed???  Maybe I'm misunderstanding that. 



 


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Teresa

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Reply with quote  #184 

***EDITED: Please note, Cystinuria has NOT been confirmed to follow this model, but some suggest it's the most likely place to start looking.
This is just a theory (based on x-linked recessive theory).

A female can be the following configurations
Xn = normal female  This female would be a single gene carrier
Xa = carrier gene
 OR
Xa = carrier  This would be a double carrier (both x genes carrying the C+)
Xa = carrier

OR

Xn = normal  This female cannot pass on any C+ genes
Xn = normal
Bred to a normal male:
Case one: Females would be 1/2 carriers and 1/2 clear
               Males would be 1/2 affected and 1/2 clear
Case two: All females would be carriers and all males would be affected.
Case three: No affected dogs or bitches.

If the male was positive, the scenerio would change:
Case one: Females could either be double carriers or single carriers.
               Males would be half affected and half clear.
Case two: All females would be double carriers and all males affected
Case three: All females single carriers and all males clear

Someone double check me. I did this rather quickly...


Even a double carrier female does not seem to be affected...


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EXCMastiffs

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Reply with quote  #185 
My personal opinion is that if this disease followed a method easily figured out by using a Punnett square, UPENN would already have a mode of inheritance?

I think continued testing, possibly a better test or something that can provide information on affected bitches, if indeed they are affected as more than a carrier yet don't test positive is probably our best bet.

For now - keep submitting urine and provide as much data as possible - it's the best we can do.

It is also going to be helpful to allow for open discussion of affected dogs and treating one another with kindness and respect so that people WILL continue to come forward with information that might be vital to people making decisions, etc.

Heather


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Teresa

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Reply with quote  #186 
  Heather...I couldn't agree with you more. It would be awesome if it was as simply as punnet square genetics, but we know, it's not. The general consensus is it's "kinda" like it, but not predictably so. That's why we keep saying it's NOT strictly a sex-linked recessive model. That would be just way too easy sadly enough. Realistically, it's probably a mosaic of issues and that makes it SO hard!! I think the only hard and fast rule with this disease is don't breed positive males. Other than that, it's anyone's guess....

  I also agree with being supportive of those that discover it in their babies. It's heartbreaking enough without the Mastiff community going into attack mode. We just MUST keep testing and working on answers...

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steveoifer

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Reply with quote  #187 
Don't breed positive males.

Any female breeding (creating) a positive male, should not be bred again and all progeny from her get should not be bred. Any dog/bitch stemming from her (i.e. children & grandchildren) should not be bred.

Since this is not an airborne disease, it could be erradicated if breeders were to follow strict breeding guidelines, but we all know this won't happen.

Don't breed to any affected dogs (males).
Don't breed bitches that produce affected males.
Follow the get of affected bitches and stop breeding them.

If this was done, the cystinuria numbers would drop dramatically.

Test, test, test!

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For the betterment of the breed

"Above all, a uniform type should be aimed at by breeders and uniformity of type can only exist in a proportionate ratio in the purity and distinctiveness in any breed"!.........M. Moore
"If breeds did not adhere to a specific shape, form, and colour range, or if breeders disregarded this blueprint, the breed would degenerate to the point that it would hardly resemble the breed at all. Selective breeding does not just create breeds- it preserves them as well." Breeding purebred dogs inherently means accepting limitations on your freedom to just breed anything...Catherine McMillan
" A reinforced consolidation of the American and British standards could be the basis for restoring our breed to the gladiatorial glory of its ancient past, in capability if not in usage".....Norman Howard Carp-Gordon
"I can live with doubt, or not knowing, rather than to have answers that might be wrong"...Richard Feynman
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steveoifer

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Reply with quote  #188 

Quote:

Thanks Steve.
Just a few clarifications for those that don't understand pH. When Steve says lower pH, he means more basic which is actually higher on the pH scale. Water is roughly 7, highly basic is 14. A C+ dog needs to be higher than 7. Acidic is below 7.



Reduce acidity is what I meant. A more alkaline PH will reduce stone formation. This will also skew testing results and produce more negatives in otherwise positive dogs!


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For the betterment of the breed

"Above all, a uniform type should be aimed at by breeders and uniformity of type can only exist in a proportionate ratio in the purity and distinctiveness in any breed"!.........M. Moore
"If breeds did not adhere to a specific shape, form, and colour range, or if breeders disregarded this blueprint, the breed would degenerate to the point that it would hardly resemble the breed at all. Selective breeding does not just create breeds- it preserves them as well." Breeding purebred dogs inherently means accepting limitations on your freedom to just breed anything...Catherine McMillan
" A reinforced consolidation of the American and British standards could be the basis for restoring our breed to the gladiatorial glory of its ancient past, in capability if not in usage".....Norman Howard Carp-Gordon
"I can live with doubt, or not knowing, rather than to have answers that might be wrong"...Richard Feynman
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Teresa

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Reply with quote  #189 
Quote:
Any female breeding (creating) a positive male, should not be bred again and all progeny from her get should not be bred. Any dog/bitch stemming from her (i.e. children & grandchildren) should not be bred.


VERY good advice Steve. I know how hard that decision is for breeders though. My Foxy's mom threw several C+ boys from her first litter. Foxy was from her second litter and bred BEFORE the breeder knew her girl threw C+ boys. I LOVED my red-headed girl, but spayed her anyway. It was NOT an easy decision and I can tell you I debated back and forth for several weeks before I resigned myself to what I had to do. Since there are still so many questions, I admit trying to justify why it might be okay, but in the end I just couldn't go there....

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steveoifer

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Reply with quote  #190 
Addendum:

Methionine levels can also affect test scores.

http://en.wikipedia.org/wiki/Methionine

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For the betterment of the breed

"Above all, a uniform type should be aimed at by breeders and uniformity of type can only exist in a proportionate ratio in the purity and distinctiveness in any breed"!.........M. Moore
"If breeds did not adhere to a specific shape, form, and colour range, or if breeders disregarded this blueprint, the breed would degenerate to the point that it would hardly resemble the breed at all. Selective breeding does not just create breeds- it preserves them as well." Breeding purebred dogs inherently means accepting limitations on your freedom to just breed anything...Catherine McMillan
" A reinforced consolidation of the American and British standards could be the basis for restoring our breed to the gladiatorial glory of its ancient past, in capability if not in usage".....Norman Howard Carp-Gordon
"I can live with doubt, or not knowing, rather than to have answers that might be wrong"...Richard Feynman
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Teresa

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Reply with quote  #191 
Hi Steve,
If I remember correctly, that's one of the ingredients in that supplement (Nutrigras) that was the problem.

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margelutz

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Reply with quote  #192 
    Today at 01:46 PM
Reply with quote #191



Addendum:

Methionine levels can also affect test scores.

 
Hi Steve ,so when ,you say affects scores !
Does this mean its a false Positive ??
 
Or we just hurried the positive along ? And its still a generic .
Problem???  and a Positive dog ,that should not be bred ??
Marge


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steveoifer

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Reply with quote  #193 

I believe it can create a negative test result, thus skewing the actual genetic condition of the dog.


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For the betterment of the breed

"Above all, a uniform type should be aimed at by breeders and uniformity of type can only exist in a proportionate ratio in the purity and distinctiveness in any breed"!.........M. Moore
"If breeds did not adhere to a specific shape, form, and colour range, or if breeders disregarded this blueprint, the breed would degenerate to the point that it would hardly resemble the breed at all. Selective breeding does not just create breeds- it preserves them as well." Breeding purebred dogs inherently means accepting limitations on your freedom to just breed anything...Catherine McMillan
" A reinforced consolidation of the American and British standards could be the basis for restoring our breed to the gladiatorial glory of its ancient past, in capability if not in usage".....Norman Howard Carp-Gordon
"I can live with doubt, or not knowing, rather than to have answers that might be wrong"...Richard Feynman
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steveoifer

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Reply with quote  #194 

Dear Mr. Oifer,

it was good to talk with you on the phone last week and thanks for your interest and your follow up email.
Here a couple of responses:

The nitroprusside test has been proven to be an excellent screening test for the severe form of cystinuria like in the Newfi. With respect to Mastiffs we believe that we have recognized most of the affecteds based upon our studies
.  However the recent trend to change diets before testing may have caused some to be showing negative results.  We are also unsure if there are any Mastiffs that could become positive after testing initially negative (however, older dogs block less likely). Finally drugs and supplements may change the results. Therefore a more reliable test would be desirable.
We can do urinary amino acid quantitation which permits not only a more specific determination of cystine but also the other related amino acids known as COLAs (cystine, ornithine, lysine, and ornithine) which are also leaked in the urine in patients with cystinuria. We have done that on quiet a few samples and found good correlation between those and the nitroprusside test results. The amino acid quantification is $150 per dog (same test in humans charges $450).

genome and SNP chip analysis of Mastiffs

A decade ago it was hard to imagine that much of the genome could be analyzed on individual dogs. The analysis between affected and unaffected males and unaffected (and that one affected) females will now be doable particularly after the software algorhythm and the actual SNP chip used today has been greatly improved over the past version.  Typically anywhere from 30 to 100 animals are totally needed.  Currently we are able to offer 100,000 Single Nucleotide Polymorphisms (SNPs) for ~$1000 which includes the DNA extraction, sample preparation, SNP chip, computer analysis of these results per dog and as a groups between affecteds and unaffecteds (major software and hardware needs and genome informatics people) and overhead (25%) to do research at Penn.  These studies are hopefully resulting in a marker for better/molecular genetic screening and help pin point us to the responsible mutant gene(s).  As you know the fact that only males are affected with cystinuria (not only stone formers) is particularly unique to the Mastiffs and a few other breeds and may further our knowledge overall in human and animal health.

We really would greatly appreciate your kind support and can provide more information to make this possible.
Indeed we all thank you in advance for your generous support.

Kind regards
Urs


Urs Giger, PD Dr. med. vet. MS FVHDipl. ACVIM and ECVIM (Internal Medicine
 and ECVCP (Clinical Pathology)Charlotte Newton Sheppard Professor of 
MedicineSchool of Veterinary Medicine at the University of Pennsylvania3900 
Delancey Street, Philadelphia, PA 19104-6010phone   215 898 8830; fax  
215 573 2162giger@vet.upenn.edu; penngen@vet.upenn.edu; 
http://www.vet.upenn.edu/penngen



steve oifer wrote:


It was good speaking with you the other day. You've cleared up some important questions that's been asked by a number of concerned fanciers in Mastiffs.
 
Is the nitroprusside test the only available test at present, or is there another more accurate test about, albeit more expensive?
 
What is the cost of a single genome workup for an individual dog?
 
Just trying to get a scale of economics regarding research costs.
 
Thanks again,
 
Steve Oifer

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For the betterment of the breed

"Above all, a uniform type should be aimed at by breeders and uniformity of type can only exist in a proportionate ratio in the purity and distinctiveness in any breed"!.........M. Moore
"If breeds did not adhere to a specific shape, form, and colour range, or if breeders disregarded this blueprint, the breed would degenerate to the point that it would hardly resemble the breed at all. Selective breeding does not just create breeds- it preserves them as well." Breeding purebred dogs inherently means accepting limitations on your freedom to just breed anything...Catherine McMillan
" A reinforced consolidation of the American and British standards could be the basis for restoring our breed to the gladiatorial glory of its ancient past, in capability if not in usage".....Norman Howard Carp-Gordon
"I can live with doubt, or not knowing, rather than to have answers that might be wrong"...Richard Feynman
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steveoifer

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Reply with quote  #195 
Quote:

urinary amino acid quantitation



It would appear that any dog in doubt could take this test to confirm cystinuria.

There are very little excuses for not testing, or not validating a questionable result with this "other" test!

ALL studs used for breeding should be tested, in this poster's opinion!

By ALL I mean ALL! NO exceptions!!!

It would also be nice to get confirmed evidence, that the urine being tested has come from the dog named on the test!


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For the betterment of the breed

"Above all, a uniform type should be aimed at by breeders and uniformity of type can only exist in a proportionate ratio in the purity and distinctiveness in any breed"!.........M. Moore
"If breeds did not adhere to a specific shape, form, and colour range, or if breeders disregarded this blueprint, the breed would degenerate to the point that it would hardly resemble the breed at all. Selective breeding does not just create breeds- it preserves them as well." Breeding purebred dogs inherently means accepting limitations on your freedom to just breed anything...Catherine McMillan
" A reinforced consolidation of the American and British standards could be the basis for restoring our breed to the gladiatorial glory of its ancient past, in capability if not in usage".....Norman Howard Carp-Gordon
"I can live with doubt, or not knowing, rather than to have answers that might be wrong"...Richard Feynman
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SilverKnight

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Reply with quote  #196 
Well Steve, I can get you confirmed evidence if you like, but I think that might be a bit pointless wouldn't you say?

Am I misunderstanding this statement? because I can also assure you that it is possible as I have two separate test results to prove just that. UPenn did do both tests, so I will have to assume that they have mis-typed this sentence or that my reading comprehension skills have dropped considerably.

Quote:
We are also unsure if there are any Mastiffs that could become positive after testing initially negative (however, older dogs block less likely)



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steveoifer

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Reply with quote  #197 
I believe that Giger is referring to dogs that do not have cystinuria that turn into cystinuria dogs!

He is not referring to false test negatives that can in fact become positive!

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For the betterment of the breed

"Above all, a uniform type should be aimed at by breeders and uniformity of type can only exist in a proportionate ratio in the purity and distinctiveness in any breed"!.........M. Moore
"If breeds did not adhere to a specific shape, form, and colour range, or if breeders disregarded this blueprint, the breed would degenerate to the point that it would hardly resemble the breed at all. Selective breeding does not just create breeds- it preserves them as well." Breeding purebred dogs inherently means accepting limitations on your freedom to just breed anything...Catherine McMillan
" A reinforced consolidation of the American and British standards could be the basis for restoring our breed to the gladiatorial glory of its ancient past, in capability if not in usage".....Norman Howard Carp-Gordon
"I can live with doubt, or not knowing, rather than to have answers that might be wrong"...Richard Feynman
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steveoifer

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Reply with quote  #198 

I've truncated the next response from Dr. Giger, but you'll get the general message.
 
Dear Mr. Oifer,

Support could greatly advance our efforts in the elucidation the mechanism of cystinuria in Mastiffs and related breeds and thus find better means to control this problem in the breed.  Moreover, some of the samples, data, and information can also be used for other projects.  However, the fact that we are also proposing to completely define the phenotype of cystinuria which is complicated in such hereditary disorders where diets and and other environmental influences are affecting the clinical picture is a particularly strong point of our studies. The combination of amino acid analysis, diet challenge, and genome wide scan will most effectively and likely bring results.  In fact I strongly believe your support may have far more reaching effects as it will likely also help elucidate cystinuria in other breeds.  It will also hopefully bring the first test to the Mastiff breed to properly manage cystinuria in the breed.


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For the betterment of the breed

"Above all, a uniform type should be aimed at by breeders and uniformity of type can only exist in a proportionate ratio in the purity and distinctiveness in any breed"!.........M. Moore
"If breeds did not adhere to a specific shape, form, and colour range, or if breeders disregarded this blueprint, the breed would degenerate to the point that it would hardly resemble the breed at all. Selective breeding does not just create breeds- it preserves them as well." Breeding purebred dogs inherently means accepting limitations on your freedom to just breed anything...Catherine McMillan
" A reinforced consolidation of the American and British standards could be the basis for restoring our breed to the gladiatorial glory of its ancient past, in capability if not in usage".....Norman Howard Carp-Gordon
"I can live with doubt, or not knowing, rather than to have answers that might be wrong"...Richard Feynman
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