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SEVEN more KIT mutations (Dominant White)

JUST published on-line today!! Wiley Interscience - Animal Genetics [url]http://www3.interscience.wiley.com/journal/122386234/abstract[/url] The equine KIT gene is now officially the most mutated gene documented in livestock!! Sadly, this is not an open access journal, so only the abstract is publicly available :o( LUCKILY, I was blessed to have one of the authors graciously share with me an advanced copy of the submitted manuscript a few months ago, with the request that I keep the info confidential [b]until[/b] it published on-line. I have done my best to relay the most important information in an article available via the Dun Central Station web site. This article does not cover all of the KIT gene mutations, such as Tobiano and the suspected KIT mutation for Roan. It primarily covers Sabino 1 and the now ELEVEN documented Dominant White mutations. I was able to make contacts to get permission to use photos of some of the horses from this latest study. But, of course, there are still many that I was unable to get photos of for my article for various reasons, such as I was not able to determine the identities of some of the horse families to know who to contact, they are European horses, etc. I have seen the photos included with the published manuscript, though. I just don't have permission to reproduce them in my article, which is a bummer, because the range of expression for at least the [i]W5[/i] and [i]W10[/i] mutations is quite varied ... from minimal sabino-type pattern to nearly or all white! But there are some pics of a few of the Thoroughbreds from the family with one of the [i]W[/i] mutations, though. My article can be found here as a downloadable PDF. [url]http://www.duncentralstation.com/DunArticles.html[/url]

accphotography Fri, 05/15/2009 - 15:05

Samantha was on the case (of splash) the last time I talked to her and if anyone can find it, she can. :bounce

This is just remarkable.

I wish they could test Sunday Silence for the DW's. I really, really think he was one. There is a large family of whites in Japan that just must be DW.

duncentralstation Fri, 05/15/2009 - 15:44

For whatever reason, KIT mutations seem to run amok (sp?) in the Thoroughbred breed! It would not surprise anyone if the American White horses were a W mutation, either, of course.

I've a feeling Airdrie Apache's line could be identified as a W mutation as well, though anything is possible, and it could be deemed a sabino mutation if homozygotes are viable.

I'm hoping Samantha finds the Splash gene quickly, too! We have just a very few Morgans that I think would qualify as Splash (based on phenotype alone), and others that sport rather minimal splash-type traits, but have not proven to produce "in your face splash" in their lines. Meaning the bloodlines are quite common, but nothing obvious has been identified. Just a few horses with some facial white, a partial blue or blue eye here or there, and some stockings.

I tend to err on the side of caution and not assume these rather minimal traits are splash at all, but are perhaps some form of sabino that can cause blue or partial blue eyes. But that's just me.

Morgan Fri, 05/15/2009 - 15:50

[quote="duncentralstation"]
I tend to err on the side of caution and not assume these rather minimal traits are splash at all, but are perhaps some form of sabino that can cause blue or partial blue eyes. But that's just me.[/quote]

I tend to call them splash by definition of splash being sabinoish with blue eyes Basically untill they've worked out splash and sabinio I think of them as two baskets that I throw the patterns into, red apples and green apples, and sometimes I have ones thats kind of both and just pick a basket. :lol: (or call it both is it's blaring obvious that there are traits of both)

duncentralstation Fri, 05/15/2009 - 16:12

[quote="accphotography"]Curious... Are Puchi Trap and Nightlight confirmed heterozygous dominant white? Do you know if they tested Faux Finish?[/quote]

Looks like my connection dropped when trying to post my reply to this,so now I have to start over! :BH

I don't know if Faux Finish was included in the study or not, but I may be able to find out when I contact the owner again. I couldn't ask direct questions at the time because I didn't know what she did or did not know about the study findings at that time.

Of the 4 horses from the W5 family that were pictured in the original manuscript, none were Puchi Trap or Nightlight. So I admit that I basically guessed that the two I pictured in my article are likely W5 ... and I fully plan to try to verify that, and post updates to the article as required.

Puchilingui was definitely one of the horses pictured, so I have no doubt that he was found to be heterozygous W5. I have a strong feeling that Puchi Trap is also W5 to be honest.

At the moment, I cannot find the notes I jotted down, but of the 4 horses of the W5 family pictured in the original study, I am thinking that I identified all but one of them. That one was an all white, so no distinguishing markings to go by on that one!! There is also a palomino with plentiful white body markings, but don't have the name handy (in the notes), and the other one shown was found to not have the [b]W5[/b] mutation ... and I'm pretty sure that one, a bay, is Sinatra's Reply, by Puchilingui, out of Blue Eyed Angel. The pic in the study was of a mature looking horse. On the breeder's site, there is a foal photo only (both pics showing the left side). But the markings match quite perfectly as far as I can tell.

You can see the foal pic of Sinatra's Reply here (two pics actually, a front shot w/dam and the left side shot):
[url]http://www.angelfire.com/on3/TrueColour…]
I would say Sinatra's Reply got Mommy's white pattern gene. Which may be splash? Or some other gene that includes blue eyes.

I'm still wracking my brain for the palomino's name ... darn it all!!

BTW, once I can get back with the breeder and see if she was ever sent results on the horses tested, if she can find out from the researchers, and if she will enlighten me with the info, too, I'll update the article. Probably by including an additional supplemental file, rather than changing the existing file, though.

RiddleMeThis Fri, 05/15/2009 - 16:29

[quote="duncentralstation"][quote="RiddleMeThis"]I believe the palomino you are talking about is Sato.
[img]http://www.blazingcoloursfarm.com/Satoa…]

[b]YES!!! And BLESS YOU[/b] for putting me out of my misery!! I knew it was a short, simple name, but was totally blanking.

And the photo I left in the above quote is the one shown in the original manuscript.

Thanks![/quote]
You are very welcome. I knew who he was the second you said palomino with plentiful white as he is the only one I know of that could possibly fit that description, though I admit I was hoping there was another LOL.

Thank you VERY much for typing up that article it is an absolute DREAM. Thank you!

duncentralstation Fri, 05/15/2009 - 16:43

[quote="RiddleMeThis"]
You are very welcome. I knew who he was the second you said palomino with plentiful white as he is the only one I know of that could possibly fit that description, though I admit I was hoping there was another LOL.

Thank you VERY much for typing up that article it is an absolute DREAM. Thank you![/quote]

Well, perhaps not as much white, but I do believe that Midas is quite likely W5 ...
[url]http://www.angelfire.com/on3/TrueColour…]

He is out of Puchi Trap, who I also strongly suspect is W5.

I have sent of an email to the breeder at True Colours Farm to see if she has ever received results of the study on the horses, find out which were included in the study, etc. So, hopefully I'll know more soon.

I'm sure I should probably have waited until I had all the info, but I've been sitting on this study/paper for a couple of months already, and I am NOT a patient person!! :lol:

accphotography Fri, 05/15/2009 - 23:06

Donna is a member here as well. Many of us know her and her horses quite well. :lol: One of the members here has a daughter of her stallion (Guaranteed Gold) and I will be breeding my mare to him in '10 or '11. :lol:

Yes, thank you very much for all of this. It is extremely helpful in many ways.

Sara Sat, 05/16/2009 - 20:09

[quote="accphotography"]Donna is a member here as well. Many of us know her and her horses quite well. :lol: One of the members here has a daughter of her stallion (Guaranteed Gold) [/quote]

*raises hand*

:bounce :bounce :bounce

it's meeeee! And anyone who might want a GG baby needs to hop on it now before it's too late! My filly would be thrilling even plain bay (well, as you all know I actually prefer bay to palomino...) but we're really going to turn heads in the hunter ring with her golden color. She's almost done shedding (thank goodness two year olds shed faster than yearlings) and then I'll post new pics.

lillith Sun, 05/17/2009 - 05:21

Are all these DW kit mutations homozygous lethal then?

and are there tests?

and if so will the tests tell you which DW gene you have?

This is very interesting, from there is no DW to 10 versions in a year.

duncentralstation Sun, 05/17/2009 - 08:40

[quote="accphotography"]Donna is a member here as well. Many of us know her and her horses quite well. :lol: One of the members here has a daughter of her stallion (Guaranteed Gold) and I will be breeding my mare to him in '10 or '11. :lol:

Yes, thank you very much for all of this. It is extremely helpful in many ways.[/quote]

I've still not gotten a response to my private emails from Donna, but she could be away, my emails were spammed, etc. I don't want to be a big pest and send a bunch of "why haven't you replied" emails in case she's away, of course, so I'm being patient ... after all, some people do have a life away from the computer. ;)

Although I'm not a TB person, I must say that I do really like the looks of the horses produced from this line. And I'm not talking about their colors, either.

duncentralstation Sun, 05/17/2009 - 09:09

[quote="lillith"]Are all these DW kit mutations homozygous lethal then?[/quote]

They are all [b]predicted to be[/b] homozygous lethal. Without breeding trials, it cannot be proven beyond a doubt. And breeding trials require a lot of jumping through hoops to get permission to do (animal experimentation), and with each of these mutations being so rare (not a lot of horses for each mutation), there really aren't a lot of horses to do breeding trials with.

Below is what I wrote in a post to a Yahoogroups list that I run on the topic of homozygous embryonic lethal ....

[i]"The KIT mutations that are currently being designated as "W" are *predicted*
to be homozygous embryonic lethal based on the lack of KIT protein produced
by the individual mutations. It is *predicted* that in homozygous form, not
enough KIT protein would be produced for the embryo to survive.

During these studies, using certain processes, they could see just how
diminished the production of KIT protein was when heterozygous to predict
that not enough would be produced if homozygous for the embryo to survive.

I keep stressing "predicted" because without breeding trials, this cannot be
100% proven at this time. But it can be predicted with a reasonable
accuracy based on the tests they ran showing the reduced production of KIT
protein when heterozygous.

I would have to wonder if any of the "W" mutations were to successfully produce
a live "WW" offspring of their specific mutation, would the designation be
able to be legitimately changed to sabino??? I have not asked this question
of the researchers directly, but .... would they/could they change it?"[/i]

[quote="lillith"]and are there tests?[/quote]

Tests for these mutations are not likely to be made "widely commerically available", I wouldn't think, because of the rarity of each mutation. BUT, with that said, I do know that the Camarillo White people did arrange to have a few horses tested. Tosso Leeb (one of the study's authors) worked with Michal Prochazka (Pet DNA Services) so they could test a couple of horses for the W4 (Camarillo White) mutation. Two different Amercian White mares are owned by Camarillo White breeders. As I understand it, both mares were tested, and neither has the W4 mutation. The resulting white foal from the mating of a Camarillo White stallion and one of the American White mares was tested for the W4 mutation. The white foal was found NOT to have the W4 mutation ... thus it must have inherited the as yet unidentified white gene from its American White dam.

[quote="lillith"]and if so will the tests tell you which DW gene you have?[/quote]

Just guessing, but I am assuming that the above mentioned testing was specific for the W4 mutation found in the Camarillo White Horses ... not for all of the W genes. I am not sure how it would work if a person had a horse and wanted them tested for any/all of the W mutations. Not sure how costly that might be.

If anyone wanted to find out what could be done in the way of testing, I would strongly encourage them to contact Tosso Leeb directly. His email address is available on the Wiley Interscience web page containing the abstract of the original manuscript.
[url]http://www3.interscience.wiley.com/jour…]

During my correspondence with Tosso, I found him to be extremely easy to communicate with and very helpful, as I did pick his brain about some of the technical stuff regarding the homozygous embryonic lethal and some hypothetical situations.

[quote="lillith"]This is very interesting, from there is no DW to 10 versions in a year.[/quote]

There are a total of [b]ELEVEN[/b] DW mutations (just to clarify), the one Sabino mutation (so far), Tobiano, which is believed to affect KIT, and Roan is also believed to be a KIT mutation or to affect KIT function.

That makes for a total of [b]FOURTEEN[/b] mutations of KIT or affecting KIT function ... for now, that is! I've a feeling more will be found in time. After all, there are the American White Horses, one or two more TB families with white patterns that could very easily be KIT mutations. And who knows what other white patterns that may not even produce nearly or all white patterns, but rather just white markings.

That gene sure does like to mutate!! :lol:

duncentralstation Sun, 05/17/2009 - 09:29

No, I didn't know that Donna was a member of this board at first, so my emails were sent directly from my email program.

I had previously contacted her directly via email anyway, to get permission to use some of her horses' photos for my article anyway. I didn't have any probs with communication that way at that time, but one never knows when spam filters will peg you as a spammer, though!!

Again, she could simply not be checking emails at the moment for any of a number of reasons, so I'll try to remain patient, especially thru the weekend.

lillith Sun, 05/17/2009 - 09:56

Thanks for the answers, I read your article and it answered most of the Q's anyway :oops: sorry should have read it first. Very well written BTW, I like your clear explinations of the types of mutation, I was kind of aware of the types before but had never had it spelled out so clearly. The diagrams are great.

[size=85]when are you doing the rest of the genes?[/size] :lol:

anyway thanks for the information. KIT does seem very predisposed to mutation, instreding.

The comment about the number (thanks for the correction) was just that when I started spoonberg said dominant white existed and everyone else said that was out of date. Things do change fast. Its the great thing about this topic, you can never ever know it all. :toast to all those trying. :D

duncentralstation Sun, 05/17/2009 - 10:06

[b]ATTENTION [i]Riddle Me This[/i]!!![/b]

I see that you've posted about the article and the study over on the PedigreeQuery site's forum!! I am not a member of that forum and really cannot justify joining yet another forum (no time).

I see some questions being raised there that I might be able to answer, so I'll post my responses here and you are more than welcome to relay them (copy/paste/quote) over on that forum if you like.

[b]Question: Who are the unnamed horses in the article with the W6 & W7 mutations?[/b]

Answer: They were indeed NOT identified in the original manuscript. None of the horses' identities were revealed, which I believe is common practice. I don't know if the researchers [i]can[/i] identify them legally. (I did not ask for horses' identities, as I assumed they cannot tell w/out written permission from the owners.) So, contacting them may not help ... but it cannot hurt to ask, I suppose. The worst that would happen is they would tell you they cannot tell you, right?
I was able to identify Puchilingui and the others of that family myself simply because I recognized them from their photos and could easily match them to those photos. My [i]guess[/i] is that neither of the W6 or W7 families include Airdrie Apache, as there were so very few horses of either family included in the study. Only ONE horse for the W6 "family", and just two horses for the W7 "family" (with only one of them having the W7 mutation). It would be my guess that the Airdrie Apache family is one of the other two families mentioned that have white patterns which have not yet been identified. But all of this is really just guesswork on my part.

[b]Question: My Blue Eyed Baby was asked about specifically.[/b]

Answer: I would guess that she is NOT a DW mutation, based on her blue eyes (found her photo on PedigreeQuery.com). But that's a guess only. Blue eyes does not appear to be trait of any of the DW mutations as far as I'm aware.
One of the horses pictured (left side of the horse) in the original manuscript as NOT having the W5 mutation was a bay with white markings. This horse appeared to be adult or young adult. Dipped looking facial white, four white legs up to knees and hocks, white spot(s) on the side of the neck.
On the True Colours Farm site, I found pics of Sinatra's Reply as a foal ... sired by Puchilingui, out of Blue Eyed Angel. One photo shows this foal photographed from the left side. The markings look identical to me. So this foal most likely got his white patterning from his dam, Blue Eyed Angel, who may be splash or some other mutation with splash-like traits.

[b]Question: Would a foal resulting from the crossing of two different W mutations be viable if it inherited each of the parents' mutations? A "mixed homozygote", if you will.[/b]

Answer: I actually did ask this question of the researchers, and the answer was a very mixed answer. In general, the answer would be "probably not". However, with certain combos, it could be possible in theory. It [i]might[/i] (stress on "might") be possible depending on which two mutations were combined, and if each of them would allow for the production of enough KIT protein to support life. The type of each of the combined mutations would likely be key. The mutations that are missense mutation, for example, might provide the greatest chance for a viable mixed homozygote, for example, IF the amino acid that is substituted is close enough in function to the one it replaced. But this is all quite highly speculative and theoretical, of course.

Again, feel free to relay any of this that you like. Feel free to copy and paste (quote) me directly if you like.

duncentralstation Sun, 05/17/2009 - 10:18

[quote="lillith"]Thanks for the answers, I read your article and it answered most of the Q's anyway :oops: sorry should have read it first. Very well written BTW, I like your clear explinations of the types of mutation, I was kind of aware of the types before but had never had it spelled out so clearly. The diagrams are great. [/quote]

No biggie on asking Q's before having read the whole article! There is a lot of reading there, so I completely understand!

[quote="lillith"][size=85]when are you doing the rest of the genes?[/size] :lol: [/quote]

:rofl I actually have attempted to create a graphic depiction of the chromosomal inversion for Tobiano! But I'm not quite happy with it yet. I haven't attempted other genes, partly because I don't have all the info for all of them (such as total number of exons for each gene), but it would be interesting to see them all laid out as simple graphic depictions, wouldn't it?!!

[quote="lillith"]anyway thanks for the information. KIT does seem very predisposed to mutation, instreding.

The comment about the number (thanks for the correction) was just that when I started spoonberg said dominant white existed and everyone else said that was out of date. Things do change fast. Its the great thing about this topic, you can never ever know it all. :toast to all those trying. :D[/quote]

No biggie on the number 10 vs 11. I just get anal sometimes. :oops:

Hey, I admit that I was one of those people who didn't think there was a true "white" gene existed!! And look at just how very wrong I was to think like that. Then again, like most people, I didn't understand/was not aware of the genetic/scientific definition of what a "white" gene was, either. Like most folks, I thought that if the horse wasn't totally, 100% white, it couldn't be a "white" gene. When the first study came out, I scratched my head over it for a few days. I couldn't stand it any longer than that, and I set about asking the researchers why "W" and not Sabino. I had to rearrange my way of thinking once I had the explanation. It's still weird to me at times, but I accept it because it is based on science and precedence that were previously set within the scientific community.

lillith Sun, 05/17/2009 - 10:28

I kinda argued that too we call white sabino so why not stick with Sbnumber for the names? i guess the DW are similar and their probable homozygous lethality + the way they make for a homozygous Sb1 effect when heterozygous makes sense to name them differently.

Interesting about R Khasper, there is a lot of sabino in his pedigree (Khembosai is in there somewhere I think??) so I though he would be Sb1 or a similar sabino gene but homozygous where the others weren't. I guess the white horse would have popped up more in that family not just in him and his progeny if that were the case what with the specific 'sabino' breeding going on.

lillith Sun, 05/17/2009 - 10:36

Hmm seems intron mutations have more effect than generally considered, three DW genes and grey all attributed to intron mutations although the mutation affects the reading of the exons at least in the DW genes. if im right?

RiddleMeThis Sun, 05/17/2009 - 11:27

[quote="duncentralstation"][b]ATTENTION [i]Riddle Me This[/i]!!![/b]

I see that you've posted about the article and the study over on the PedigreeQuery site's forum!! I am not a member of that forum and really cannot justify joining yet another forum (no time).

I see some questions being raised there that I might be able to answer, so I'll post my responses here and you are more than welcome to relay them (copy/paste/quote) over on that forum if you like.

[b]Question: Who are the unnamed horses in the article with the W6 & W7 mutations?[/b]

Answer: They were indeed NOT identified in the original manuscript. None of the horses' identities were revealed, which I believe is common practice. I don't know if the researchers [i]can[/i] identify them legally. (I did not ask for horses' identities, as I assumed they cannot tell w/out written permission from the owners.) So, contacting them may not help ... but it cannot hurt to ask, I suppose. The worst that would happen is they would tell you they cannot tell you, right?
I was able to identify Puchilingui and the others of that family myself simply because I recognized them from their photos and could easily match them to those photos. My [i]guess[/i] is that neither of the W6 or W7 families include Airdrie Apache, as there were so very few horses of either family included in the study. Only ONE horse for the W6 "family", and just two horses for the W7 "family" (with only one of them having the W7 mutation). It would be my guess that the Airdrie Apache family is one of the other two families mentioned that have white patterns which have not yet been identified. But all of this is really just guesswork on my part.

[b]Question: My Blue Eyed Baby was asked about specifically.[/b]

Answer: I would guess that she is NOT a DW mutation, based on her blue eyes (found her photo on PedigreeQuery.com). But that's a guess only. Blue eyes does not appear to be trait of any of the DW mutations as far as I'm aware.
One of the horses pictured (left side of the horse) in the original manuscript as NOT having the W5 mutation was a bay with white markings. This horse appeared to be adult or young adult. Dipped looking facial white, four white legs up to knees and hocks, white spot(s) on the side of the neck.
On the True Colours Farm site, I found pics of Sinatra's Reply as a foal ... sired by Puchilingui, out of Blue Eyed Angel. One photo shows this foal photographed from the left side. The markings look identical to me. So this foal most likely got his white patterning from his dam, Blue Eyed Angel, who may be splash or some other mutation with splash-like traits.

[b]Question: Would a foal resulting from the crossing of two different W mutations be viable if it inherited each of the parents' mutations? A "mixed homozygote", if you will.[/b]

Answer: I actually did ask this question of the researchers, and the answer was a very mixed answer. In general, the answer would be "probably not". However, with certain combos, it could be possible in theory. It [i]might[/i] (stress on "might") be possible depending on which two mutations were combined, and if each of them would allow for the production of enough KIT protein to support life. The type of each of the combined mutations would likely be key. The mutations that are missense mutation, for example, might provide the greatest chance for a viable mixed homozygote, for example, IF the amino acid that is substituted is close enough in function to the one it replaced. But this is all quite highly speculative and theoretical, of course.

Again, feel free to relay any of this that you like. Feel free to copy and paste (quote) me directly if you like.[/quote]
Thank you VERY much DCS! I have been meaning to come over here and ask those questions of you, and I just kept forgetting. And do not worry about not being able to justify joining that forum, as even if you did join you probably wouldnt get approved for a LONG time. I was waiting for about a year before I finally tried emailing the Admin over there to finally get approved, and did. Though ACC has done that as well and still has not gotten approval.

Thank you for your time writing that and this new response and I will GLADLY post it over there for you!

duncentralstation Sun, 05/17/2009 - 14:48

[quote="accphotography"]I bet W7 is Deebrand.[/quote]

GRRRR!!! I am SO mad at this forum!! Not the people, but I had logged in, was researching and typing at the same time, when when I hit Submit, it must have logged me out automatically at some point, and lost everything I had typed!! :BH

I looked up Deebrand on PedigreeQuery.com, but no photo of her was included. In the info section it mentioned she produced a white filly. Checked her progeny and found Turf Club, with photo. [url]http://www.pedigreequery.com/turf+club[…]

Not the same photo as shown in the study's collage of horses, but the base color of chestnut and the overall expression does appear the same or very similar. So perhaps Turf Club is the W7 horse, which would mean that her dam, Deebrand, does not have the W7 mutation as stated in the manuscript.

In my searching, I found links to some other photos of Turf Club ...

[url]http://www.finalturngallery.com/g2/main…]

[url]http://www.finalturngallery.com/g2/main…]

[url]http://www.finalturngallery.com/g2/main…]

Interestingly enough, while searching to see if I could find the same pic as that shown in the study (which I didn't find), I did run across this ....

[url]http://www.blazingcoloursfarm.com/dora2…]
This colt is out of the Deebrand daughter, Adorable, who appears to have splash-like leg white markings and some belly spots. She does have some facial white, but not dipped looking like that of splash, so I'm not sure what white pattern she truly expresses ... although if Turf Club is indeed the W7 horse, then we know it's not W7.

This colt is sired by Sato, who we know to be W5. So I would guess this colt is most likely an all white expression of the W5 mutation.

accphotography Sun, 05/17/2009 - 15:05

Hmmm. I made a mistake. I was thinking Deebrand was mostly white, but she is not. I do have a photo of Deebrand, but she is virtually solid (a tiny star and stripe). I suppose it's possible that Deebrand was negative and Turf Club or one of her others was positive. However, Deebrand has produced several colored foals, who have also produced colored foals, so it seems highly unlikely that she herself would be negative if it were her.

Hmmmm.

duncentralstation Sun, 05/17/2009 - 15:08

OOPS!!! I just realized that I was looking at the horse in the W6 photo, not W7!!

The horse shown for W6 looks like it could possibly be Turf Club, as that one showed speckling like she has, while the W7 horse is whiter.

So, everything I posted in the previous post is basically worthless. Only one horse was available from the W6 family ... and that could be Turf Club. Does anyone have a photo of Deebrand? I couldn't find one.

I don't know who the W7 horse might be, but it is surely not related to the W6 horse, as they have them separated by family relationship.

duncentralstation Sun, 05/17/2009 - 16:15

I would seriously doubt that the W6 or W7 mutations would be the Airdrie Apache line, as they would surely have been able to get samples from more than just one or two horses to study.