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MDR1 - can we eradicate?


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#61 Mark Billadeau

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Posted 08 May 2018 - 09:59 AM

Read this
http://www.institute...nomic-selection
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#62 Smalahundur

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Posted 08 May 2018 - 12:45 PM

Unless we are looking at diversity as part of our breeding strategy, two breeders that dont breed alike can both be decreasing diversity. Breeding for the same type decreases diversity. Diversity of a closed gene pool cannot increase; all we can do is slow the decrease in diversity.

Okay, I will sound like cpt. Obvious here, but the other thing we can do is allow the gene pool to be open.
In that light I think ROM should be less prohibative, at least here it is quite expensive. Here in Iceland the national stockdog organisation became part of the ISDS a few years ago, and a lot of dogs have been ROMed since then.
But the negative effect is that breeders seem to prefer dogs with ISDS reg (because the the pups have that registration, and the perceived stamp of quality) . Making the breeding pool smaller for no good reason.
I prefer diversity, and a factor in my selecting a dog (for work I don't breed) is as little inbreeding in its pedigree as possible.

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#63 Journey

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Posted 08 May 2018 - 09:56 PM

Dominant does not exist. It's blended. Check.

So if we use this terminology, based on the video, how is this one going to be differentiated from the others (simple recessives) on the website? To alert and educate people that there is a difference with this one, that it's not just a matter of being a carrier.

And is the HEF going to come out with breeding recommendations? As it has with other issues.
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#64 GentleLake

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Posted 09 May 2018 - 09:40 AM

Dominant does not exist. It's blended. Check.

 

So if we use this terminology, based on the video...

 

Unless I completely misunderstood the video, that's not what it says.

 

It says that some alleles are dominant but that others are blended (aka some other terms that Dr. Redfield rejects). The focus of the video is on the other blended expressions of allelles that aren't simple dominant, and the preface to the video by Dr. Beuchat clearly states the same thing.

 

Most people understand that dominant alleles are expressed whether there is one or two copies at a locus, whereas recessive alleles are only expressed if there are two copies of that allele. This clear difference between dominant and recessive expression is certainly true for some genes, but in reality the situation can be much more complex. (emphasis added)


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#65 Journey

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Posted 09 May 2018 - 09:56 AM

I was speaking specifically related to the MDR1 and being implied I was wrong in calling it an incomplete dominant, per the video. I searched a good bit but could not locate anything else that says incomplete, co, semi are incorrect terms to use.
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#66 Mark Billadeau

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Posted 09 May 2018 - 10:33 AM

were the authors of these websites geneticists?

Many of the websites I saw using these terms were marketing tests. What language does WSU use?
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#67 Kelliwic Border Collies

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Posted 09 May 2018 - 10:36 AM

The only wording still under discussion is the prevalence rate, which we hope to have resolved soon.

 

Hi Eileen,

 

What info is being used to estimate the prevalence rate? It seems that few Border Collie breeders, especially working breeders, are testing for MDR1. Up till the beginning of this year, I believed--as do or did many others--that MDR1 did not seem to exist in Border Collies. Five of my dogs have been tested for it, only because it was part of a package deal; if I'd had to pay separately, I doubt that I'd have tested for it. They were all N/N, which simply reinforced what I already believed--up till a few months ago. 

Thanks!

 


Megan Q.


#68 Mark Billadeau

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Posted 09 May 2018 - 10:48 AM

read the section on mdr1 posted here: https://bordercollie...netic-diseases/
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#69 Journey

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Posted 09 May 2018 - 12:44 PM

A quick snip from WSU and the language they use:

It is confusing to refer to genetic results as positive or negative because the meaning in some contexts can be ambiguous. Similarly, the MDR1 mutation is a dominant genetic trait, so the use of the word carrier for heterozygous dogs is incorrect. Both heterozygous and homozygous dogs can show drug toxicosis when given P-glycoprotein substrates.
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#70 Mark Billadeau

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Posted 09 May 2018 - 12:53 PM

WSU does not call it incomplete dominant like the other websites.
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#71 Journey

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Posted 09 May 2018 - 01:12 PM

And your point is? They call it dominant. Which is lacking on the HEF site.
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#72 Mark Billadeau

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Posted 09 May 2018 - 01:20 PM

According to the WSU published research Homozygous mutants have no p glycoprotein production while heterozygots have some p glycoprotein production. Does that sound like the mutation fits the definition of dominant?

A dominant gene would yield exactly the same phenotype with 1 or 2 copies of that gene.
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#73 Journey

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Posted 09 May 2018 - 01:30 PM

Mark, this is pointless. I don't care what it sounds like, it's what they said. I'm going to just pull from the alternative testing and be done with this. I completely understand the lack of information on the HEF site.
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#74 Mark Billadeau

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Posted 09 May 2018 - 02:12 PM

You want the HEF website update to be accurate (recessive is not accurate and it has been corrected) but then you want us to post inaccurate information (dominant is not accurate based upon WSU published peer reviewed research). You want the HEF website to educate using up to date information and genetic language (not just lay descriptions) but then you dont want us to use correct genetic language.

I too find this pointless.
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#75 Eileen Stein

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Posted 09 May 2018 - 03:40 PM

What I had found were inconsistencies within the MDR1 part vs the others. I found no mention of this being an *incomplete dominant* gene.  If education (among other things) is the reason for the HEF  why no mention of the type of gene. And why no breeding recommendations? How many other diseases are there that are caused by an incomplete dominant gene? I am aware of 3 I think. Are there more? Wouldn't this be reason enough to at least mention it? Bring it to the attention of folks?

 
The scientists on the Board did not want to use the term "incomplete dominant," because they don't consider that terminology to be totally accurate, both for the reasons expressed in the video Mark linked to, and others that are more complicated (but I'm happy to try to explain them if you want).  We thought the education mission would be better served by explaining the effect of the heterozygous and homozygous forms of MDR1rather than using a problematic term.
 

No, no allegation. I thought we were talking the breed as a whole until Mark specified the NC.  Made me wonder if a national champion gets a pass on being healthy just because of the work? If that's the case then why do we bother? Or the flip side is we don't need to worry about the gene pool being reduced as we'll do it ourselves with unhealthy dogs. 
. . . .
 
What is the take away? Carry on, no big deal? Until the breed begins to have the issue of 70% affected or m/n? Is it that a national champion is implicated that we don't want to try to eradicate this while we can? Or is it really no big deal?

 
You seem to think that HEF is fiddling while the breed burns, and I'm sorry for that, but there are many considerations involved in arriving at a breeding recommendation (and not all of the diseases we list have a breeding recommendation).  First of all, these dogs are not unhealthy.  They have a genetic flaw, as all of us do, but the vast majority of them will live out their lives without any ill effects from this genetic flaw.  I think any recommendation we might arrive at has to take this fact into account -- the approach of trying to totally eliminate a gene mutation from the breed is impractical and carries its own risks.  Many other facts have to be weighed in also, including prevalence, which is not easy to determine, and which can change over time, although it's not going to jump from its current level to 70% of the breed during the time we are deliberating.  The fact that a national champion carries the mutation is something that must be taken into account, but only because that dog will likely be bred from more than other dogs, which will have some bearing on prevalence.
 
I think you're probably right that this discussion is not going to result in the immediate satisfaction of your concerns, but be assured we are taking those concerns into account, and will try to deal with them in the best way possible.

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