DNA tests and Laboratories

[mijke]

Originally Posted by canislupus

@Mijke: what do you think about this? I am not experienced with validation of those tests. Is she right? How can we get to know if the test will be really good or if there will be more or less wrong results. (before we have to pay lots of money...)

Hi Tanja,
For me it is more easier to ex-plain in Dutch! But I ‘ll try to explain it simple in English language.

Personal I think something else is mentioned with “validation” between the DNA dwarfism test and de DNA HD test.

When genetic specialist are doing research for a genetic mutation it costs years.
I’ll try to explain how it did work with the dwarfism test:

The specialists did start to compare DNA of dwarfs, their parents (= carriers), brothers, sisters with other dogs (which they did know they were free). This research did take years and a lot of blood samples! And in this case the genetic specialist could locate the mutation! And they were lucky that the mutation for dwarfism is “single“ recessive mutation. (I don’t know the correct translation)
When they did know where to look for this dwarfism gen mutation, they could compare the mutated gen of the GSH with a SWH who was a proven carrier (parent of a dwarf) and then the test was also validated for SWH.

After that I only had to find only 1 CsW dwarf or 1 proven parent of a dwarf to validate the dwarfism test for CsW breed. (because the mutation was "single" already known and theyonlydid have to compare)

But for a DNA HD test it will be maybe more complicated! Because a lot of genetic specialist expect that HD is not caused by a “single” recessive mutation but will have “multi factor” causes.
Maybe there is not yet found an exact location of a gen mutation. And they have found only the differences in DNA between HD A and HD D/E dogs.

That also explains why they first need 24 CsW’s to see if the differences are the same. And when that is a fact, later on they can compare a lot more CsW’s with and without HD to find the exact differences. And so in future they maybe can find the DNA mutations that causes HD. But that will take a lot of time!!

But maybe I am wrong! So please Ina, correct me when there are other reasons why they need more Csw’s for validation.

[michaelundinaeichhorn]

Originally Posted by mijke

But maybe I am wrong! So please Ina, correct me when there are other reasons why they need more Csw’s for validation.

HD is for sure caused by several genes, that has to be so because there are more than one bone involved in the joint and there are different forms of causes of HD (to small Caput femoris, to low Norberg degree and so on). Though it is no longer discussed that HD is a genetic desease there are factors like too much training or too highly energetic food in the growth period that have a great influence on the severeness of the genetic caused desease.
So there is not only one reason or one gene mutation that has to be found but very likely the combination of genetic factors that is the reason, at least several different genes. That of course makes research much more difficult, takes much more time and dogs.
Anyway every genetic test that has been validated on one breed has to be checked on every new breed because there are defects with identical symptoms but caused by different mutations. But when you already have one working test you look in every new breed if the genes for the defect are the same or not. If you look for one mutated gene like in the dwarf test you only need one dog, if you look for different genes like in polygenic defect like HD you need more dogs because one dog with HD E may show a defect on the genes 1+3 and the other on 2+4 (just as an example, I am not that far in detailes about this test), or the combination of 1+4 causes severe HD, the combination of 1 + 2 doesn´t.
So as far as I understood they only need 24 dogs to check if they show the same mutations but about 200 to validate a working test.

[Juniorwolf]

Hello Ina and/or Mijke,

I am trying to follow this post, but sometimes it is a little too technical for me... something I would like to know(I think Mikael also asked this question earlier) is how excat will a HD DNA test be, I mean if they only have found the difference between HD A and HD D/E ? does this mean that, when the test is validated, it will only be possibe to say if the result is very good or very bad(not as excat as xray) ? ...or did I misunderstand ?

Thanks for keeping this very interesting topic public, so I(and others) can follow this

Greetings Rolf

[mijke]

Ina did have contact with the university.
So I think she can explain the best , what on this moment the (validated) DNA test for the GSH exactly can tell about the HD of a individual GSH.

[michaelundinaeichhorn]

I just asked them to make sure I didn´t get anything wrong.
In future it will be possible to make a selection of studs or dogs with this test and you can already start in puppyage. You can say which dogs are likely to get HD, which pairings are not sensible to make or which dog should be left out of breeding.
At this actual period you need both the x-rays and the blood to control the test (Yes I also think they can´t charge 300 Euros for that at the moment!!) and there is no result of breeding-selection at the moment in GSH, what means it will take several years till you will have statistics.
I still think this is a test of very high value for every breed but I also agree that there is no sense to pay for it as long as we have to pay for it on our own because the benefit at the moment for the breeder himself is low and our breed isn´t able to bring up this amount of money for a research projekt.

So in my opinion we should start with a blood bank, make a database for that dogs and wait for interesting research projects and the result of the test in the GSH.
DNA-tests will be the future and a good thing to avoid health problems in breeds so we should get ready for that.

[Juniorwolf]

Hi Ina,

Thanks for your answer

So this is how I understod it : for many years to come, xrays will still be necessary and sometime in a far away future, it will be possible to give only HD-results "good" or "bad" by DNA, but not more specific than that... and maybe in an even further away future it will be possible to give exact(A,B,C,D,E) HD-results from DNA ...for both GSD and CSW !

Please correct me if I am wrong ?

Greetings Rolf

[saschia]

Hi Rolf,

I don't think you'll ever be able to give HD A/B/C/D by DNA, as there is a lot of environmental influence on the definitive results. But you'll be able to say if the dog or it's offspring will be more or less succeptible to having dysplasia or not. You can never rule out damage made by irresponsible owners (like hard training of obese dog during it's development).