Due to decreasing use over the years, I have decided to disable the forum functionality of the site.

Forums will still be available to view but new posts are no longer allowed.

Sabino-1 and DW?

tjuri April 17, 2010 February 22, 2011

Forums

If you look into this article http://www.duncentralstation.com/PDF/KITGeneMutations-Castle.pdf" onclick="window.open(this.href);return false; ...there are figures shown. Fig#1 shows the KIT gene with its 21 exons. Fig#2 shows where Sabino-1 is located - exon 17 is skipped, means SB1 is KIT minus exon 17. All of the DW mutations except one (!): Fig#13 have lost some parts of KIT including #17, so it is not possible that they carry SB1 on that same gene...[b]because SB1 is KIT minus exon #17 not minus any other exons! [/b] BUT every horse has two copies of KIT and theoretically it might be possible another mutation like SB1 can be found there? BUT then again: "Heterozygous W horses produce less of the KIT protein compared to solid colored horses with only wild type (ww) KIT alleles. [b]This leads to the conclusion that one wild type allele produces enough KIT protein for the heterozygous Dominant White horse to be viable, healthy, and fertile enough to survive and reproduce.[/b] Based on studies of mice with W mutations, it is predicted that Dominant White mutations in horses leads to embryonic death when homozygous. The embryo cannot survive due to insufficient production of the KIT protein. Deficiency of KIT protein production prevents the proper development of cells that are vital to survival of the embryo." [b]Since any KIT gene with SB1 is no longer a "wild type" anymore because #17 is missing[/b], I doubt that it is possible for a horse to carry SB1 AND Dominant White... [b]Or is it??????[/b] Is there any info if some of the horses in the latest DW studies have tested positive for DW [b]and[/b] Sb1?????

horsegen Sun, 04/18/2010 - 23:14

A horse cannot carry DW and Sb1 [i]on the same chromosome.[/i] However, every horse carries two copies of each chromosome, so it would be possible for a horse to have both mutations, one on each chromosome. In that case, the dominant white phenotype will mask the effects of the sabino, and the horse will simply appear dominant white.

accphotography Sun, 04/18/2010 - 23:36

So, could tobiano and SB1 exist on the same chromosome? What about roan and SB1?

I feel like I'm missing something here.

Monsterpony Sun, 04/18/2010 - 23:50

If tobiano is a mutation [i]near[/i] KIT rather than in it, then I would think that you could have them on the same chromosome if a cross-over occurred at the right place.

accphotography Sun, 04/18/2010 - 23:51

So if that's what allows it to happen with tobi, then what about roan and SB1? This was debated years ago and I thought we had all decided on the answer... but I think now apparently things have changed.

tjuri Mon, 04/19/2010 - 09:25

Horsegen, thanks for your input! :flower
So there have already been horses tested positive for carrying both mutations?

It is this quote from the recent DW study that gives me a hard time, since a chromosome with sb1 is an altered chromosome and no longer a wild type allel:

[quote]This leads to the conclusion that one wild type allele produces enough KIT protein for the heterozygous Dominant White horse to be viable, healthy, and fertile enough to survive and reproduce.[/quote]

With sabino and DW there are often the same areas/exons missing or changed, so some areas would not produce any proteins anymore at all, especially exon #17... if that areas are affected by mutations on BOTH chromosomes. I hope I could explain myself properly... :? ;)

horsegen Mon, 04/19/2010 - 12:51

[quote]So, could tobiano and SB1 exist on the same chromosome? What about roan and SB1?[/quote]

Technically, tobiano and SB1 could exist on the same chromosome. The tobiano mutation is a large inversion of ECA3 that occurs just before the KIT protein. It is thought that this inversion moves some sort of regulatory element away from KIT so that it cannot be "turned on". But KIT is still there, and intact. So you could theoretically have the inversion, and the missing exon of KIT on the same chromosome. I don't know of any horse that's ever tested that way, so I don't know if one exists (yet), but it could happen. The phenotype would probably be more tobiano, since the regulatory element will have been moved away from KIT, so even with the SB1 mutation, that copy of KIT wouldn't be turned on enough to show the effects of SB1. That's just my opinion though, based on biological knowledge of how gene regulation works.

With roan, since we don't know what that mutation is yet, I don't think I could say whether both could exist or not, or if they COULD both exist, whether the phenotype of one would mask the effects of the other.

[quote]With sabino and DW there are often the same areas/exons missing or changed, so some areas would not produce any proteins anymore at all, especially exon #17... if that areas are affected by mutations on BOTH chromosomes. I hope I could explain myself properly...[/quote]

I think you have the right idea. Most DW mutations involve a stop codon at some early part of the gene, like exon 4. So if a horse did have both that DW mutation and SB1 on the same chromosome, when KIT is translated, the protein will stop at exon 4, and exon 17 will never even come into play. It's sort of a moot point.

The other part of your question seems to be asking about the viability of a DW/SB1 horse if the mutations are on different chromosomes, as the DW chromosome will not produce enough KIT protein on it's own--so you're asking if the SB1 chromosome would pick up the slack, even though it's not a wild type allele? The point is that while SB1 is not technically a "wild type" allele, it does in fact produce enough KIT protein for a horse to be viable--that horse just has the sabino pattern. (Simply losing an exon doesn't normally cause the loss of the protein--just a small piece of the protein, such that it doesn't quite do its job as well.) That's why you can have homozygous SB1 horses. So even with one bad KIT protein on the DW chromosome, the SB1 chromosome should produce enough KIT for the horse to be viable. Now, that horse will LOOK dominant white, due to the masking effects of the DW mutation.

To my knowledge, no horse has ever been tested that had both. But since the only people doing the testing for DW are those doing the research on it (and I have no idea if they're also testing for SB1), it could happen. I just don't have any data on horses positive for DW.

I hope this answers your questions!

RiddleMeThis Mon, 04/19/2010 - 20:37

[quote]I think you have the right idea. Most DW mutations involve a stop codon at some early part of the gene, like exon 4. So if a horse did have both that DW mutation and SB1 on the same chromosome, when KIT is translated, the protein will stop at exon 4, and exon 17 will never even come into play. It's sort of a moot point.
[/quote] Say a horse had a DW mutation, and also had SB1 would they TEST positive for SB1?

horsegen Mon, 04/19/2010 - 23:59

Yes, no matter which chromosome it was on. Genetic tests look for DNA sequence changes. Remember, DNA is transcribed into RNA, which is translated into protein. With DW, the "problem" doesn't happen until the translation, when ribosomes get the signal to stop translating much too early. But the DNA sequence will only contain the mutations, not the problems associated with them. Does that make sense?

tjuri Tue, 04/20/2010 - 10:05

Thanks, Horsegen :D your reply was right on my questions :flower so I guess for now we can't rule out a horse as a possible DW carrier - if it tested positive for sb1 - but it is showing the phenotype of one of the known mutations for DW.
But I understand from your explanations we can rule out horses that have been tested positive SB1/SB1.

That is a bit more of the puzzle solved - for me at least!
And - yes, your reply made sense... :D

I remember there was a line of TWH posted on this board (bad memory: Pusher?) and the horses tested positive for SB1 - but some of the horses display the phenotype of DW... so maybe there are some of these examples? :-? :ymsmug:

RiddleMeThis Tue, 04/20/2010 - 10:14

[quote="tjuri"]
I remember there was a line of TWH posted on this board (bad memory: Pusher?) and the horses tested positive for SB1 - but some of the horses display the phenotype of DW... so maybe there are some of these examples? :-? :ymsmug:[/quote]These are exactly the horses I (And ACC though she hasn't posted) were thinking of with the questions. Especially since SB1 doesn't look like that in other breeds. We were wondering if it was possible they were DW in addition to being SB1.

Danni Tue, 04/20/2010 - 21:16

Wow this conversation is hurting my head, but I'm trying to follow it!!!

I've been meaning to put up these pictures for days to see what Acc thought, so now seems a good a time as any. Basically I've got used to sb1 looking a certain way, Acc said I might be looking at DW instead?

With the Gypsy cobs they obviously have many sorts of sabino type patterns but I can pick a large percentage now of ones that might or not might not test positive for sb1. The positive ones are always a loud pattern, not roan looking but definately roanish, or scetchy might be a better word. Still slightly different from a splashed white with a loud sabino pattern (might just have roaning at all the edges at the splashed white) and the sb1's are usually a bit different to that as is isn't just edges, it's the whole pattern. Anyway I can't explain it very well LOL! But these are tested sb1's (heterozygous, the homos are just white). So are these DW's too?? If so maybe the DW is coming along with the sb1....

This mare is probably the most minimal sb1 I know of so far, but still seems to fit the pattern. A harder one to pick though as she's got less pattern than most. Her colt is the one that's next and he's similar. Quite a few people test for sb1, but very few are positive. So I haven't seen any really minimal sb1's before, hence my questioning about what seems to be happening with the Gypsies.

[img]http://img338.imageshack.us/img338/2388…]
[img]http://img402.imageshack.us/img402/5181…]
[img]http://img145.imageshack.us/img145/7953…]
[img]http://img88.imageshack.us/img88/1336/d…]
[img]http://img243.imageshack.us/img243/7885…]
[img]http://img708.imageshack.us/img708/5782…]
[img]http://img301.imageshack.us/img301/7915…]
[img]http://img121.imageshack.us/img121/4796…]
[img]http://img444.imageshack.us/img444/8531…]