Talk:Lethal white syndrome

Discussion

IMHO, Lethal White affects enough horses and more than one breed, especially with its controversial, possible, (probabe??) link to the Frame Overo gene that it should be ranked medium importance. There is a DNA test as well. Seems to have the numbers, publicity and concern amongst laypeople to justify a higher ranking. (As should, when you get to them, HYPP and HERDA)

This is exactly why I asked for more input on the equine medicine articles - I knew I would mess up the importance ratings. Thanks for clarifying this. By the way, I already rated the HERDA article as low importance, but please change it if you think it warrants a higher rating. --Joelmills 02:34, 10 July 2007 (UTC)

Sigh. There is no link of LWS to the frame overo gene, as this article goes to great lengths to explain, and this common misunderstanding is the cause of dangerous and wasteful breeding practices. I agree with the medium importance. Dcoetzee 06:38, 10 July 2007 (UTC)

Well, the frame overo thing is a dispute between UC Davis and the University of Minnesota, but we won't argue that here. Montanabw^(talk) 21:36, 10 July 2007 (UTC)

There is no dispute, and I think it's worth arguing here if it affects the factual presentation of the topic. I'm not aware that UC Davis has ever made a statement after Minnesota published their results contesting them in any way - Laurie Fio's work clearly predates the blood test and Minnesota's findings by several years, and had no basis in experimentation. Dcoetzee 23:03, 10 July 2007 (UTC)

If anybody is interested in reading a slightly more recent article about this, there is one from the Canadian Veterinary Journal here, entitled "Foal with Overo lethal white syndrome born to a registered quarter horse mare", which would seem to bear out what Dcoetzee is saying. The gene that OLWS has been linked to is the endothelin receptor B gene, which interestingly is the same one that causes a similar disease in humans, Hirschsprung's disease. --Joelmills 23:25, 10 July 2007 (UTC)

---

This wikipedia article itself sidesteps this issue and I am not going to join the controversy in the article at all, just discuss it here. But please note I said LINK, not CAUSE. And a UCD researcher is the one who found the Hirschsrpung-like gene, see http://www.vetmed.ucdavis.edu/CCAH/Genetics/Person_Metallinos-Bannasch.htm Joel, bless ya, but the article you cite says "The mare's sire, a registered American paint horse, was sorrel with an Overo pattern." (grin) You have landed yourself in the middle of horse politics, m'laddie, so hang on and get out yer popcorn, it's going to be a heckuva ride!

I am just throwing in my oar because I have been studying various genetic diseases in various horse breeds for a while now and I am beyond fed up with the attitude of breeders (of any breed, take your pick) and their routine state of claiming total shock that their horse/program/breed could possibly have genetic problems. (hey Joelmills, are the dog people this way too?) Besides being flat out dishonest, or at least a major case of psychological denial, this attitude has slowed research-- we'd have tests for all this stuff -- and sooner -- and better understood -- if not for the denial and covering up. (far easier to shoot, shovel and shut up) And yes, I've read the MN study, bought and paid for by the APHA, which had a financial interest in its outcome. The UC Davis stuff would be removed in a lawsuit if it were made up of whole cloth and unsupported or discredited. And they have the DNA test. So, obviously, there is still a controversy and the issue isn't fully settled. I've read the stuff on the APHA site and indeed, Overo doesn't "cause" LWS, but there IS some kind of link. see http://www.vgl.ucdavis.edu/service/horse/coatcolor.html#lwo

What people don't seem to "get" is that frame overo is not a simple dominant gene, it is more complex, (I can't find anything explaining if we even know if it is a gene complex like sabino, or if its an incomplete dominant, or even a recessive, but it obviously is not a simple dominant like tobiano. One site said that as many as 10 genes could make up overo, but it has no cites to genetics literature, just mentions Sponenberg.) but whatever it is, it can "lurk" in solids (as anyone who ever had a cropout QH under the old white rule knew only too well) and in tobianos (and a link to how a tobiano can throw an LWS foal-- see here http://www.horsequest.com/journal/educate/lethaltt.html (. Even Fio said, " In overo to overo breedings, there is no firm evidence that a lethal white foal is a definite possibility in every cross." http://www.vgl.ucdavis.edu/~lvmillon/overo.htm Though some articles suggest it's a dominant, seems LWS acts like a recessive as it must be from both parents to produce an affected foal. Clearly it isn't just the color-producing part of the overo gene alone, as there would never be an overo-colored horse if the color gene itself "caused" LWS. And one web site I ran across suggests the test seems to have now demonstrated that there are overo-patterned horses without being carriers of LWS.

However, LWS never appears in breeds of horses that do not produce overo coloring, for example, Clydesdales carry sabino, but not overo, and they do not have LWS. Neither do Arabians or Andalusians or Welsh ponies, or any other non-overo-producing breed. It's mostly a Paint/Quarter Horse thing. So is some kind of link to overo, we just don't know what it is, and the defensiveness of Paint breeders does not change reality. Saddlebreds, who produce tobianos, don't have LWS. Neither do shetland ponies, who also have tobiano (though it apparently has appeared in minis).

Sorry that I am ranting, I'm just tired of people who don't like reality. Overo and LWS are somehow connected. Correlation is not causation, but you cannot deny that the correlation exists. Joel, forgive us for dragging you into this. If I may pun a bit, I'd love a more black and white answer to this question! Montanabw^(talk) 05:03, 11 July 2007 (UTC)

I see what you are saying, Montana, and I missed that part of the article saying that the mare's sire had an overo pattern. I didn't think that the frame overo trait might have a polygenic base, and that accounts in part for my misunderstanding of the question. If it was a single gene, and that gene is different from the endothelin receptor B gene, than the two are not linked (unless they are linked). If multiple genes are involved in the frame overo trait, than they could be linked. It seems to me that the recent completion of the first draft of the equine genome gives some hope that these questions will be answered. In the meantime, we depend on seven measly journal articles, the most recent five years old, and only two of which we can access fully. This is one of the frustrations of trying to seriously write a vet med article - sometimes there is a real dearth of research. Regardless, don't worry about dragging me into all this. I find this kind of thing fascinating, all the more so because I don't know anything about it. --Joelmills 03:59, 12 July 2007 (UTC)

Agreed that more research is needed. Genetic linkage is an interesting thing, and what does make LWS puzzling is that the condition only shows up in horse breeds who also sometimes exhibit the overo pattern; the reason for the correlation is hard to figure out, but it's there. Bottom line on ALL the genetic diseases in various purebred animals is that it doesn't help when breeders just stick their heads in the sand and pretend it doesn't exist. Montanabw^(talk) 19:06, 12 July 2007 (UTC)

I agree that a correlation exists, and it is certainly the case statistically that a random horse carrying LWS is currently much more likely to be overo paint than any other breed. But now that a blood test is available, and that test has demonstrated that it's unpredictable which horses carry it, sound breeding practices should be based on the test results, and not any phenotype. You might use breed to determine which horses to test. To accuse MN of fabricating results for the APHA's financial interests is silly - I think they would value their reputation as a research institute more. Dcoetzee 19:52, 12 July 2007 (UTC)

Facing the facts

I have sympathy for people who have overos and have to constantly deal with uninformed people who think the color causes the disease. Obviously that isn't true; I believe we did point out in the article that many overo horses test negative for LWS. However, facts don't stop the doggedly uninformed. I also know people who dismiss every horse in a breed I know particularly well, in part because some representatives have carrier genes for four genetic diseases that can't yet be tested, and only one that can, so my sympathies only go so far. My axe to grind on the entire topic of genetic lethal diseases (and this includes any breed of horse or dog) is that people need to be honest and to put the good of the breed ahead of personal greed. That starts with accurate statements and not hiding from some of the uncomfortable truths. That is why I like to work on wikipedia, it is the search for truth that counts. To say there is NO connection to overo is to distort the truth. The truth is that now there is a test, people need to use it, and yes, even people with solids and tobianos.

A university does not falsify results, please do not put words into my mouth. What I am saying is that it is a reality that who pays for research cannot help but have an interest in its outcome and exert subtle and not so subtle pressure on which results may be focused upon and which are filed in the back drawer. The tobacco industry banked on that factor for years. The APHA was happy to get a test, I am sure U Minn found the proper markers, but then the money seems to have dried up -- We still haven't figured out why there is a connection to overo ancestry, even if not visible in the phenotype of every carrier. We still don't even have a good study to determine if overo is a gene complex, and incomplete dominant, or what.

That said, it also matters that what goes here is stated as carefully and fully and accurately as it can be. I just spent a good two hours last night checking the statements in the article against what the research and sources actually said and had to correct a great deal of text in the article that didn't have it quite right (probably including a few of my own earlier edits) The disease, to the best of my knowledge, has not ever appeared in a breed of horse that doesn't have overo members of that breed, and every known LWS foal has at least one overo ancestor. For example, there has never been a LWS Saddlebred or Clydesdale. Curious to know if any other breeds besides Paints and Quarter Horses (or crossbreds with those breeds in them) have had LWS other than apparently one mini.(?) Montanabw^(talk) 04:32, 13 July 2007 (UTC)

New research and updating

I know this hasn't been touched in a long time, but it should be addressed again. This NIH/NCBI/OMIM article [1] discusses the polymorphism on endothelin receptor type B (EDNRB) that is responsible for lethal white foal syndrome and the frame pattern. Frame and LWFS are the same; ambiguity arises from "cryptic frames" which can be masked by other white patterns, which may have them miscategorized as "tobiano" or "sabino" or even solid. However, the gene that causes frame also causes (causes, not is linked to) lethal white foal syndrome. I never say "overo." Scroll down to "Animal Model" to read the pertinent section. Countercanter (talk) 19:07, 1 September 2008 (UTC)

To add -- [2] The dissertation of Dr. Brooks is also more clear than many editorialized articles. The pertinent text is in Section 1.

In the coming days I hope to get to this article. What needs to be included is: LWSF=frame; but the term overo does not mean frame, and studies are limited by classifications of horses based on registration records.Countercanter (talk) 19:18, 1 September 2008 (UTC)

Go for it! That would be terrific! On the way, though, check out the latest round of revisions (and sources) in the overo article. We may need to properly cross-reference and coordinate these articles. (You fix this one, I steal your best stuff for Overo? LOL!) Also, can we clarify the dominant/recessive or whatever is going on with LWS? Incomplete dominant? Recessive? And what about that old "Overo could be created by as many as 11 different genes" thing that was at one time on the UCD site? (What I'm wondering is if there is an argument to be made for a "research history" section, explaining all the paths this has taken from about 1998 or so until now...???) Hm. Also, UCD still uses "OLWS" as an acronym...???

I had an anon IP editor come into Overo with some new stuff, some of which was not accurate, or at least poorly worded, other tapped what you are saying, but not in a citable way, and so I made a bunch of revisions based off of UCD info, APHA publications and what I could get on PubMed abstracts. So anything you can add and source will be terrific (especially if it's on the web) What we have in the "Overo" situation (i.e the "anything that isn't Tobiano" definition the APHA used to use) appears to be as follows: 1) I haven't seen online articles in PubMed that say frame "causes" LWS per se, but they say "strongly associated," etc... however that can be explained or updated is fine with me, but I want to be real careful about quoting sources as accurately as possible. 2) The APHA is fudging in their publications, the pdf on colors says basically that LWS (or OWLS, as UC Davis calls it) isn't "caused by overo," theymake a big deal about how some "overo" horses do not carry the LWS allele -- so are they just fudging by not saying FRAME overo and thus only are technically correct for the reasons you stated (they lump sabino with overo and also include splash overo, which appears to be yet another genetic mechanism, and one linked to deafness); or are there in fact verifiable frame overo patterned horses without the allele??? Montanabw^(talk) 04:47, 2 September 2008 (UTC)

Will indeed check Overo. LWFS is recessive in that two copies of the polymorphism on EDNRB are required for the broken hardware. The frame pattern is incomplete dominant in that one copy of the polymorphism on EDNRB produces white markings, and two copies produces distinguishably different white markings. I believe that the term for multiple phenotypes being attached to a polymorphism/gene/allele is called pleiotropy, but I may be mistaken.

I don't believe that the use of OLWS by UCD is significant. I never say overo and I think it's best to use the multiple acronyms as interchangeably as possible so as not to acknowledge what may or may not be politicking.

I agree that it is in the best interest of many people to keep the waters around the term "overo" as muddy as possible. But yes, if someone is saying that not all FRAME horses carry the LWFS gene, they are mistaken. If the horse doesn't have what we call the LWFS allele, they ain't frame.

I also agree that the article would benefit from structure. This would be an article that, for truth's sake, I would be very interested in promoting as a GA.Countercanter (talk) 16:19, 2 September 2008 (UTC)

GA? That would be fun! I agree with you. I'd say go ahead and keep tweaking on it, I'll try to confine myself to wordsmithing while you get the facts straight(er) and improve the sources, and when the rough draft is redone, we can call in the WPEQ GA crew (Ealdgyth and Dana) to have them review and all that. As for details, I'm OK with using LWS. Seems to upset fewer people than OWLS. And while I can't wrap my head around how the LWS gene is both recessive and an incomplete dominant at the same time, I do agree with you that it does act as you describe and if that is what a "pleiotrophy" is, then boy that is one heckuva a plieotrophy! (grin and LOL!) By the way, I read that dissertation, what didn't make my eyes cross with its complexity was really quite interesting (though the stuff on how the DNA was analyzed went right over my head!) and is in line with other things I have read. Montanabw^(talk) 06:24, 6 September 2008 (UTC)

I'm trying to save some original content, and have utilized all the sources in the current article, plus lots more. However it's a big, well-researched genetic deal and so it sure as heck isn't going to remain in the format it's in. For what it's worth, I seldom (if ever) read the methods and materials. Sometimes it's worth checking out where they got their information, pedigree records, horses from...but unless you're DOING the tests I wouldn't bother with those sections. They're there for other people who do those tests.Countercanter (talk) 17:27, 6 September 2008 (UTC)

Appy genes

By the way, did you see the thing in "The Horse" online linking the Appaloosa LP gene to night blindness? Seems that nature does have a tendency to select against a lot of white in many ways, not just by attracting predators...? Montanabw^(talk) 06:24, 6 September 2008 (UTC)

I had seen some of that research, and I'm not surprised; I'll have to read the article! Nature has no such tendency because nature has no tendencies. Our breeding practices have a tendency to encourage changes in highly-conserved building blocks that have affects on many systems.Countercanter (talk) 22:48, 6 September 2008 (UTC)

New version

I'm pretty proud of it. I think it is VERY dense, which will be helped by pictures and having other eyes look it over. I also think that a "research history" section would be valuable. I understand that not everybody has access to the articles I do, so if questions arise I will pull the quotes and stick them in. Its impractical to include every quote for everything. So, have at it.Countercanter (talk) 22:48, 6 September 2008 (UTC)

I am impressed with your work, and I'll wordsmith a bit. If I see something that I suspect others will slap a citation tag on, I'll slap it on as a preemptive strike. It would be nice to have photos, but it might be a challenge. I hesitate to use any image of a frame overo unless we can find one where the uploader admits they have tested the horse. (For example, in cerebellar abiotrophy, the photo is of a known affected horse, taken and uploaded by the owner of the animal) It would be great if we could find an image of an affected LWS newborn foal, preferably not yet euthanized that we could put up under a Fair Use license. (Just for an example of using a Fair Use license in an article, see Khemosabi.) Another idea for an image: maybe we (well, OK, you!) could find a chart (or make one) of the mode of inheritance and upload that as an image?? Montanabw^(talk) 03:44, 7 September 2008 (UTC)

Follow up: You did a really nice rewrite! I'm now done wordsmithing, hope I didn't make any major factual screwups.I put in hidden text in a few places where I had questions, comments, or wanted to leave an explanation. Toss it once you've read it. Feel free to fix, toss or tweak anything I did. I didn't make any significant changes to your overall layout, I like it, though here and there I moved some stuff around because it seemed to read better or joined related ideas together. I added a little new material here and there. In the course of these changes, I may have messed up some of your cites, hope I didn't, you can slap me if I did. Likewise, if I reworded something to the point that it no longer accurately reflects the source, my apologies, and feel free to fix. I also "fact" tagged some stuff that I suspect that sooner or later we will be forced to footnote during GA review. No rush to get citations at this point, I won't toss anything based on a cite tag. I'll try to take care of citing all the things that I added that I didn't cite (and you can slap on more tags if you see problems), and if I come across something that helps footnote your material, I'll toss it in.

The biggest change you will notice is that I redid the lead and tossed all footnotes from the lead. The reason for this is that you did say you wanted to go for GA. Wikipedia MOS says that for a GA, the lead has no footnotes, but also that all information the lead contains is stated and footnoted elsewhere in the article. Oh and the lead ideally summarizes all major points made throughout the article. I find this to be a pain in the butt, but it's also one of the first things the GA reviewers nag about. FYI, I just survived (barely) a GA review of Horses in Warfare, mostly thanks to Ealdgyth and Dana, but if you want to see what an article that is GA and being prepped for FA looks like in terms of citation and such, check it out. Also note Thoroughbred DID get to FA. If you want to, also look at the reviewer stuff on the talk page and review pages. Reviewers are non-horse people, by and large...so be prepared. Montanabw^(talk) 07:56, 7 September 2008 (UTC)

The other thing is that when you cite a source multiple times, it's easier to do <ref name="whatever"/> than <ref name="whatever"></ref> I fixed all the ones I spotted. And, while this is strictly an IMHO, I think it works better to ref name multiple appearing sources by something that make them easily identifiable like an abbreviated title or author's last name instead of "1a, 2a," etc...It's not a moral issue and I realize it would be a major PITA for you to change at this point, but I label the ones I added that way. Montanabw^(talk) 08:26, 7 September 2008 (UTC)

Edit commentary

• Question about deaf LWS foals: While I'm sure it's possible that the deaf LWS foals were also splash, deafness linked to depigmentation is pretty common. We look for the simplest, logical answer.

Absent causation, correlation alone may or may not be significant. Just wondering if deafness was coincidental, or if is possibly a condition helf by all LWS foals? Wonder how many examples (if one or two, correlation is questionable, if every foal tested for hearing prior to euth was deaf, that would be more significant...)

• Meconium is there, but has become impacted wherever the innervation of the gut ends.

OK

• cecum + colon = hindgut.

Hmm. Depends on source, not worth a spat, I just hear the cecum called the "hindgut" by most of the literature on digestion in the context of horse being "hindgut fermenters" as opposed to ruminants. If the term is extended to include the entire lower bowel, whatever, just source it.

• With pleiotropy, what am I trying to prove? That the word pleiotropy means what it does, or that multiple traits are affected by the frame gene?

I think it makes sense to define the term the way you did, it made sense to explain that multiple traits are affected by the frame gene, but because it is a highly technical term not familiar to even the average horse-oriented reader, the brief explanation, even with wikilink too, was a good idea.

• Frames are visually misidentified because they are identified by humans, who are imperfect. I can try to clarify this section later.

No problem, with that explanation, we just need the source that says "humans foul up and misidentify things."

• I'm not sure how to reference the TB because it would have to go to his website, unless I get a statement from his owner.

A reference to his web site is fine. Nothing wrong with farm web sites if they are the best available source. If the source itself is questionable, then the whole statement is also questionable...

• How did the solid minis lose their citation? Where did it go? I'll have to go retrieve it.

Not sure, probably my fault when I rearranged something...source "16a" vanished prior to my editing, by the way

• I've never heard of calico either. You and I would have called it a form of sabino, but it appears the researchers found they could distinguish calico from the other patterns. It's a good study. Do you have an email address? Is it a social faux pas for me to ask?

Go ahead and shoot me an email via the "send email feature" of wiki, I don't mind. You aren't a nut! (grin)

• I very much like how you qualified the APHA quote.

Thanks

• I wish someone would make such a bold statement about the immorality of such willful, harmful crossings. It does give Punnett Squares and explains further.

Oh well, we can't have everything.

• Yes, the wording that includes Waardenburg-Shah syndrome is correct.
• Are photos from papers and journals allowed?

Check the wikipedia articles on Images, which I find confusing and byzantine. Long story short, if you can either get something released as either GDFL-licensed or public domain, then no problem. To get something that may be subject to copyright, you have to review the "fair use" policies, as there are some times when it can be done. (We get away with it on the horse biograpies because one kind of fair use is if there are NO free images available and highly unlikely to ever be)

I have more to do, of course. Countercanter (talk) 13:41, 9 September 2008 (UTC)

Of course! Wikipedia: we can quit whenever we want...after just one more edit... Montanabw^(talk) 19:32, 9 September 2008 (UTC)

Citing "cryptic frame"

The term "cryptic" is usually associated with crypsis, an evolutionary camoflague tactic. However, scientific literature has also used it to describe other circumstances. [3]Cryptic merle is applied to dogs which have the merle gene, but express it to a degree that it may be "missed" by human identifiers. [4]Cryptic cream is similarly applied to horses which have the cream gene, but express it in such a way that it may also be "missed" by human identifiers (eg. smoky black, dark buckskins). Unfortunately, I have not been able to find a written definition for "cryptic" that would allow me to extend this usage to "cryptic frame", though such horses fit the mold set above. In other words, I see that other people apply "cryptic" to misidentified coat colors, but I cannot find a source that gives such a definition. Is it inappropriate to use the term in the article? Countercanter (talk) 12:58, 1 May 2009 (UTC)

I honestly don't know. I'd say if you can't verify its use, then we can either explain it as a colloquialism, or just toss it. I'll leave it up to you! Montanabw^(talk) 03:45, 2 May 2009 (UTC)

Citing "incomplete dominant."

I think I need to remove any mention of dominance. LWFS is recessive, but frame overo is dominant, even though they are the same thing. It's super confusing and none of the reputable sources call it recessive, dominant, or incomplete dominant. Additionally, I'm not sure that the cream gene reference belongs in there. Countercanter (talk) 13:51, 1 May 2009 (UTC)

As long as we have something in practical terms explaining that BOTH parents have to have the gene for an affected foal to be born. We may need to explain that the inheritance pattern is complex and not fully understood. But as for phrasing, whatever the science supports. Montanabw^(talk) 03:56, 2 May 2009 (UTC)

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Move discussion in progress

There is a move discussion in progress on Talk:Lethal White (novel) which affects this page. Please participate on that page and not in this talk page section. Thank you. —RMCD bot 16:34, 7 November 2018 (UTC)