First Results Posted from the DCM DNA Gene Mutation Test !!

First Results Posted from the DCM DNA Gene Mutation Test !!

Unread postby trinitydobes » Wed Oct 27, 2010 8:13 pm

The Veterinary Cardiac Testing Lab has posted the first test results. The list & results so far can be seen here

http://www.vetmed.wsu.edu/deptsVCGL/doberman/TestResults.aspx

One of the things I find the MOST interesting with only a little over 30 results so far - is that by far the most are coming back NEGATIVE!! Now it is early days yet to even be thinking that these first test results are indicative of the "Big Picture" of thet TOTAL doberman population.

However if it is - then there is definitely another gene or some other genetic causitive agent at work for us to have such a high incidence of DCM in our breed.

On the Other hand - how wonderful that this first batch of tests has returned with mostly NEGATIVE results!!!

As the test are posted I will keep posting the link so we can see how as the test numbers increase, HOW the percentage of Neg/Pos-Hetero/ Pos-Homo percentages may change.

This is also why it is so Very, Very important that as many people test their dobes as possible - we need to have as many dobes from as many bloodlines as possible be tested - it does not matter if they are S/N or not breeding. If you don't want to know the results, then just tell the lab they can post the results anonymously but you do not want to know.

If we only have breeders and show people testing - this will be a very skewed sampling from the bloodlines represented in our breed.

Interesting days ahead for sure - but what a wonderful start!!! I am very ecouraged at the number of negatives, even if it is proven to not be the only genetic cause of DCM [url][/url]
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Re: First Results Posted from the DCM DNA Gene Mutation Tes

Unread postby js_finland » Wed Oct 27, 2010 9:54 pm

trinitydobes wrote:One of the things I find the MOST interesting with only a little over 30 results so far - is that by far the most are coming back NEGATIVE!!

On the VCGL/WSU dog form:
"I am requesting that the result's of my dog's genetic DCM test be made available on the WSU web site ... only if negative for the mutation"

Another reason for huge percentage of negatives so far...?
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Re: First Results Posted from the DCM DNA Gene Mutation Tes

Unread postby Weinberge » Thu Oct 28, 2010 6:16 am

"I am requesting that the result's of my dog's genetic DCM test be made available on the WSU web site ... only if negative for the mutation"


Only positive advertising ! :lol:
:lol: :lol: DIABOLIC ! :lol:
I never saw soo pathetical thing on my life !
No character power to asum the error, no love for dobermann breed. Soo much falsity !
Zero character.
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Unread postby js_finland » Thu Oct 28, 2010 9:48 am

^ On the other hand it looks like we do usually see only the nickname of the dogs so far i.e. getting more information about the dogs will not be an easy task without first finding the database of the kennel organization in question...
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About selection against mutation associated with DCM

Unread postby Sonia Dobe » Thu Oct 28, 2010 1:33 pm

Estimated Valencia:

The calculation is simple, for every negative dd there are approximately 4-5 positive Dd or DD, of which 2 are homozygous DD for the mutation . You have done a great job with your Pedigree software and anyone can anticipate about what might happen and what lines have more problems. With or without DCM test: 2+2=4.

The discovery of a nuclear DNA mutation (deletion of 16 bp, no marker) responsible for DCM in Doberman is a first step, but as already indicated in his presentation Dr. Meurs, the problem is probably more complex (polygenic). I think that early will begin to appear more papers on various aspects of the disease, and blood samples of tested dogs will be very useful.

Genetic background of Dobermann genome shows two disturbing characteristics: significant loss of alleles and intense linkage disequilibrium. As I already indicated in two previous notes, the immune system of the Dobermann is like a sieve full of holes, and breed shows worrying signs of immune deficiency. Last evaluation of impact of inherited disorders on the 50 most popular breeds, placed the Dobermann in the seventh worst place with predisposition to 53 genetic disorders (Asher et al. 2009. Inherited defects in pedigree dogs. Part 1: Disorders related to breed standards. The Veterinary Journal 182, 402–411).

Major gene responsible for the disease is discovered, and we can no longer say: "when it is discovered, we'll see”. There will be a group of breeders who will try to continue as if nothing had happened, and now they will say that “there are other genes, that all is not clear..”. There will always be reasons for unreason, but the selection will be made against the mutation, and other selection criteria will be deferred to a secondary level. Reduction of the breeding population can be drastic, because the “market” will quickly select: Who will buy a dog without a test? Who will buy a dog heterozygous defective Dd, when we do not know what will be affected? What will happen with the homozygote’s DD? Euthanized? Who will want matting a free female dd with a heterozygous defective Dd sire? Not too much. More of the confusion regarding the DCM has been cleared and now dogs without DCM test no longer be suspects, but guilty. Will the judges continue to choose winners as if nothing had happened? Probably, but winner males DD or Dd for the mutation will not very likely to be requested for stud service. By contrast, winner males dd free for the mutation will be very requested.

The problem is that reduction is not on a “genetically healthy” population, but on a population with a reduced “effective population” (Ne) and a bad genetic background. What will happen to an isolated population with a high inbreed rate is not a secret, and the scientific literature is full of examples that indicate what will happen. The situation of purebred dogs is similar to that of a widely studied model of population genetics in conservation biology: “the island model” proposed by Wright (1931) and then uses estimates of Wright's Fst (inbreeding rate) to calculate effective population Ne. I have numeric data about the effective population size Ne for the population of European Dobermann because I have calculated, but I will not give because it is useless. In any case it is very small (far less than 100 dogs). It is certain that the selection against the DCM mutation will cause problems, but the question remains whether many or few problems. Everything depends on how we do things.

Let us now make an estimate of what the baseline situation. Breeding population are distributed as follows:
Image

Most of the current population (average population between 2009 and 2001) are no breeding population, and only 20% is breeding population: 76% are females and only 24% are males. Among males 61% were “top sires” with more than 100 pups produced. It is clearly a biased sire population with a high top sire contribution.

If we project linearly these rates to the current European population, excluding population homozygous DD for the mutation, we are approximately 2012 breeding females (Dd or dd), only 354 are free dd homozygous for the mutation, but only 212 dd females are in reproductive age (2-8 years). About sires I have spoke before. Otherwise we can not forget that these available reproductive females and males are related by ascendancy: average inbreeding coefficient for the current European Population COI = 10.27 +- 4.55 %. We can not confuse wishes with reality. If this is not the numbers of a future bottleneck, it seems a lot. Selection for conformation, plus character and against DCM mutation? How many dogs? We will have to set priorities, forget the old triumphalism speeches, and adapt to reality. The market is a very severe judge, implacable.

The managing of selection program against DCM need a rational approach, and old ticks about overuse of popular sires can be dramatic in our case. Graphic bellow shows the evolution of effective population versus number of breeding females, for different number of males at breeding.
Image

Obviously biased sex mating determines a several reduction in the effective population Ne. You can also observe that for a little number of reproductive males, effective population Ne is quickly independent of number of breeding females. It's like there are 10, 100 or 5000 females, effective population is the same. If we continue to focus the selection on popular dogs, with this drastic reduction of the population expected, quickly we find more problems. I know you're not kindly of regulations, but do you understand why we should limit the number of litters per male?

You know how I think, but please read the 2008 RSPCA report (specially Chapter 4 & 5) of a prestigious group of 28 independent scientists: geneticists, animal welfare experts and veterinarians, commissioned by the Royal Society for the Prevention of Cruelty to Animals, and coordinated by the speakers: Professor David Sargan (School of Veterinary Medicine, University of Cambridge) and Professor Nicola Rooney (University of Bristol): “Pedigree dog breeding in the UK: A major welfare concern?
http://www.rspca.org.uk/ImageLocator/LocateAsset?asset=document&assetId=1232712491490&mode=prd

Are all these experts lunatics? Although it may seem a paradox, perhaps now the breed is more in danger than a month ago, when it was revealed the discovery of the mutation for Dobermann DCM. The result will depend a lot on how we handle the situation. Will we learn any day of past mistakes, or our dogs will continue to pay the price?

Amicably.
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Re: About selection against mutation associated with DCM

Unread postby Weinberge » Thu Oct 28, 2010 5:59 pm

Sonia Dobe wrote:Estimated Valencia:
You have done a great job with your Pedigree software and anyone can anticipate about what might happen and what lines have more problems.


Yes, after I get and writed in program some health informations, the program help me few years ago to saw and understood problems.
Unfortunately breeders don't still don't understood or refuse to accept the "matematics of pedigrees".
For this reason I publish and make the program FREE.

Sonia Dobe wrote:Estimated Valencia:
as already indicated in his presentation Dr. Meurs, the problem is probably more complex (polygenic).


I am not geneticist but always I said the cancer, DCm , HD and character are not black or white and have complex genetic matrices.

Then for me was clear: The inbreeding on ill lines construct fast the wrong matrices. If the matrix of disease is complete, the disease occur.

Then exist ONLY one way :must to dilute the wrong genes , avoid inbreeding on that lines. But how ? For that must to use clear matrices or the problem is almost all clear matrices was losted .

(* who know to matematically work with matrices will understood more easy how genetic work and what mean "alele genes' .)

Then I understood very well what you said regard the hetero-coefficients , and I calculated that on my program. Hetero-coefficients mean DIBERSITY.
Diversity mean no inbreeding. No inbreeding mean Diversity and result different matrix combinations. That increase chances for a good health.

(The Germans calculate that on virtual matings and named that "losted ancestors " . This TERM appear and in working-dobermann-eu site.)

*Note: That explain the HD poligenetic problem from Remijaguare and Livonija. The wrong HD appeared between two normal HD dogs. Was a matrices action , every dog writed a matrix part and the final matrix was wrong .

The problem is: Almost " all the roads go not to the Rome". Except DN and few other Italian lines, to the Rome road Go to Forell/Frankenhorst show lines too . That is a mathematically truth . The refresh is impossible between two dogs from actual show lines , because back than 4-5 generations the almost all the ancestors are THE SAME .

The race genepool is deep HURTED ! and that happened like a result of Big Breeders actions , under HIGHT LEVEL protection. Fir this reasons I can not admire their work and I can not accept their breeding way.

That ancestors are multiplied matematically, they are doubled on every new generation. That mean a arithmetic progression .
To continue mean final destruction of race genepool.
With Mathematically precision .
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Unread postby Weinberge » Thu Oct 28, 2010 8:13 pm

Dear Sonia Dobe

I read and I understood your arguments regarding the low genepool level and your future prognosis .What you said is exactly till one point.

It is true that will come the time when a healtly dog will be prefferated before a ill champion. Today is INVERSE, scores of years was inverse.
This year the IDC champions was strong criticized here and nobody defend them. Is first sign to normality, first signs this system try to purify himself.
In my opinion this represent begining of system returning to normality.

The theorys regard diversity maded by ill dobermann is false. What diversity they have ?Many of them represent only genetical & biological BOMBS

After IMENSE errors of breeding sysetm ,the genepool already is very low , the healtly lines already was losted or mixed . We don't have more reserves .Breeders still are IGNORANTS and refuse last reserves capable for REAL genetic refresh !
Only few breeders efforts can save last lines capable for REAL genepool refresh because they are more rare like pure gold .

In contrast, actual show lines have the same ancestors back by 4-5 generations . Then is impossible to discuss now about genetical diversity . The diversity already don't exist because actual show lines genes are THE SAME . They only make "little inbreeding on Adelante" or outcross on thousandths of times in Frankenhorst and Forells.

Then..to eliminate the ill dogs or ill genetic is only a PRIMORDIAL necessity of race and a purification action .
Will remained ONLY the right genes from all sides .
If that will happen in this mode, the race can reborn, healtly, super-character and beautiful.

But I have some seriouse dobts that this will happen in positive mode.
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Re: First Results Posted from the DCM DNA Gene Mutation Tes

Unread postby Didier » Fri Oct 29, 2010 11:59 am

trinitydobes wrote:The Veterinary Cardiac Testing Lab has posted the first test results. The list & results so far can be seen here

http://www.vetmed.wsu.edu/deptsVCGL/doberman/TestResults.aspx

One of the things I find the MOST interesting with only a little over 30 results so far - is that by far the most are coming back NEGATIVE!! Now it is early days yet to even be thinking that these first test results are indicative of the "Big Picture" of thet TOTAL doberman population.

..................................................
.....................................................
..................................................


But the problem it is that the test results are public posted only if the owner accepts, thus the results will not be obligatorily indicative of Dobermann population.

I hope that of reality quantified statistical on the Dobermann population could be public posted by this laboratory.


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Unread postby Sonia Dobe » Fri Oct 29, 2010 1:51 pm

Valencia wrote:This year the IDC champions was strong criticized here and nobody defend them. Is first sign to normality, first signs this system try to purify himself.


The IDC shows increasingly resemble more to the bad American Western movies, where the script and main characters are always the same, and the outcome, without moral dilemmas, is predictable from the first minute: always wins the sheriff or the 7th Cavalry.

As Bmguillespie has noted, usually we have selected an anatomical type too heavy and tall, which represents a genetic disadvantage. I do not observe any functional advantage in this type of dog: increased energy expenditure and lower reaction rate for the same target.

I have analysed the pedigree structure of actual population and most (3/4) population have gone through a “genetic funnel” dominated by three dogs of the eighties (in order of influence): Graaf Quirinus v. Neerlands Stam > Hertog Alpha v. Le Dobry > Prinz v. Norden Stamm. Influence of Prinz v. Norden Stamm is quantitatively less important than two others, but no qualitatively because two influent modern top sires, Baron Nike Renewal and Gino Gomez del Citone, are strong related with Prinz by ascendance. Remained genetic diversity in European bloodlines, it is only in clean lines of working dogs from Bingo v. Ellendong origin. Otherwise the remaining solution will be the crossing with other breeds. There are equations that have no solution.

I want to express public tribute to the few European breeders, as Bitten Jönsson, that have bred with great sacrifice to keep their bloodlines healthy, enduring a lot of misunderstanding against the dominant tendency. Time had given them the right, and today they are the exiguous European reserve of genetic diversity for overcome this delicate situation of the breed.
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Unread postby Ronindobe » Fri Oct 29, 2010 2:33 pm

It is true that test results by name are the property of the owner and so are published only by their permission. However the publishing of nameless data and trends does not require that consent. Population issues will be examined within the constraints of who actually tests their animals.

Yes indeed! Bitten and Lars deserve the respect and support they have earned over 20+years of their work at Jotunheim. They are thoughtful, intelligent, honest, caring, hardworking stewards of the Dobermann. Bitten has been valuable beyond description in increasing my personal insight and I am proud to call her mentor and friend. Their program may well be a spring of "fresh water" to improve the pool. Certainly their insight to future combinations and program design has credibility and should be sought out. Against much resistance and criticism they continue to fight the good battle for the breed. Thank you from my heart, B!!

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Unread postby jotunheim » Fri Oct 29, 2010 4:09 pm

Sonia Dobe wrote:I want to express public tribute to the few European breeders, as Bitten Jönsson, that have bred with great sacrifice to keep their bloodlines healthy, enduring a lot of misunderstanding against the dominant tendency. Time had given them the right, and today they are the exiguous European reserve of genetic diversity for overcome this delicate situation of the breed.


Thank you - for this estimed recognision.
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Unread postby jotunheim » Fri Oct 29, 2010 4:11 pm

Ronindobe wrote:Yes indeed! Bitten and Lars deserve the respect and support they have earned over 20+years of their work at Jotunheim. They are thoughtful, intelligent, honest, caring, hardworking stewards of the Dobermann. Bitten has been valuable beyond description in increasing my personal insight and I am proud to call her mentor and friend. Their program may well be a spring of "fresh water" to improve the pool. Certainly their insight to future combinations and program design has credibility and should be sought out. Against much resistance and criticism they continue to fight the good battle for the breed. Thank you from my heart, B!!

8)


Thank you Greg - for your support and kind words.
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Unread postby Ronindobe » Fri Oct 29, 2010 4:42 pm

No thanks is necessary. I can not adequately express my gratitude for the gift of your time and tolerance. With your help I learn faster, grow stronger in the Dobermann world, in short I do a better job. You are gold to me. My hope is that our circle becomes larger and smarter.

The rest is mere statement of truth.

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Unread postby trinitydobes » Fri Oct 29, 2010 4:57 pm

I have sent an email to Dr. Meurs to please post on the website a simple chart - with the total number of dobes testes and the total number of each category for the results - total # negative, Total # Postitive Hetero, and Positive Homo - this will allow owner & dog identity to remain anonymous - but give us a better picture of the percentages.
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Unread postby trinitydobes » Fri Oct 29, 2010 5:04 pm

double post - sorry
Last edited by trinitydobes on Fri Oct 29, 2010 5:07 pm, edited 1 time in total.
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