Silver in Icelandics

It might not be the founder effect then. I suspected, because of Dr. Ramsey and his list of breeds affected. Have you spoken to him?

As I said before I have seen it in a Silver Black mini filly.

Very interesting! Thanks for sharing the info.

I haven't contacted Dr. Ramsey, but I have seen most of his published work. I wanted to know specifically about Icelandics because of the fact that the breed has been isolated from others for over a thousand years. I figure that if Icelandics have a link between silver and MCOA, than it most likely didn't originate with the foundation of the RMHs or any of the more recent breeds such as minis and shetlands.

I've got a homozygous silver with normal eyes, so it still can't be all silver have ASD. I guess if ASD can somehow link to silver, the RMH's still have lots of it because of the founder effect and using a horse lots that had ASD and silver linked??

Or it could just be plain old linkage. If they are close together, then statistically, they would normally move together, but not in 100% of all cases. The Founder effect is tough though..a common ancestor between Icelandics and all the other breeds with silver, for over 1000 years. You're stretching so far back, this thing should be much more widespread. Along those lines, then, how many incidents are reported in non-silver horses?

Exactly. I agree the most likely explanation is linkage.

Danni- have your horses eyes been checked before? Many of the MCOA are not detectable with the naked eye. Unless the lesions cause a complete blockage of vision or retinal detachment/severe damage, you may not be able to tell they are present by checking for visual deficit. Also, in the study with several hundred RMHs, they found a family that should have been MCOA based on breeding records, but were not affected (ie- normal eye exam). There seems to be a huge variation in penetrance of the gene or a protective gene. On the other hand, you would think something would have been published by now if more silver horses had been found with MCOA outside of RMHs. I really wish I had access to some silver horses right now to take a thorough look.

One paper listed the colors of horses examined, and all those with MCOA were called silver bay, silver black, chocolate, chestnut or dark palomino. Only one silver bay was noted on the not affected list.

In all honesty I doubt you'd find a vet in Australia that knew what they are looking for. It's not really a common problem! There has been silvers in Australia for ages and eye problems haven't ever been noticed as being more prevalent in them?

So I guess as you say, my homozygous silver could have an undetectable/un-obvious form of ASD but seriously I'm not going to keep trying to look for something I can't see! I know the lady who bred my colt, she's bred dozens of silvers, I've visited her farm and I'm never noticed eye problems. I don't think I'm sticking my head in the sand, but I'm not going to look for trouble where trouble doesn't exist. It's something I keep in the back of my mind, but I still think it's mostly a RMH problem, not a silver problem. Even if ASD can link to silver, it still has to be there to link??
Cheers

Danni

Dr. Ramsey implied because the RMH registry helps pay for this research, it has only been published in that breed. This is a letter Dr. Ramsey wrote in response to an article in Horse Illustrated, which had some inaccurate information.

[i]Clearing up Misconceptions about A.S.D.
By Dr. David Ramsey, DVM

I read with interest the article entitled �Check Out Those Genes� published in the most recent edition of Horse Illustrated (Breckenridge T. Check Out Those Genes. Horse Illustrated 1999;23(3):76-84). This article discusses several known heritable (genetic) diseases affecting horses, and suggests that other less common equine diseases may also have a heritable basis. Coat color genetics are also discussed as are certain diseases that may be closely linked to specific color genes. The article was well written but several statements in print are inaccurate or incorrect.

In the original article, the author states:[/i]
�Another rare, genetically linked condition for which a reliable test will probably soon be developed is anterior segment dysgenesis. Most common among Rocky Mountain Horses, the ASD defect results in horses that develop painful and vision-limiting cysts in their eyes, or may�rarely� be born with no eyes.�

[i]The abbreviation �ASD� refers to Anterior Segment Dysgenesis, a colloquial term that includes an extensive set of developmental conditions that affect the anterior segment (front part) of the eye. There is a wide spectrum of conditions that may result from ASD�from a malformed eye that is blind at birth, to conditions that do not affect vision or the health of the eye. Contrary to the published report in Horse Illustrated, the Rocky Mountain Horse eye is virtually unaffected. With the exception of two blind horses from a population of 2500 Rocky Mountain Horses examined to date, vision is rarely affected and the health of the eye is virtually normal in Rocky Mountain Horses with ASD.

In 1996, Michigan State University began a clinical investigative and molecular genetic study of ASD. Aims of our research were to 1) describe the clinical findings in a large cross section of related horses, 2) to determine if heritability was a risk factor for the disease, and 3) to collect DNA from affected and normal horses for future comparisons of pedigree and DNA marker or candidate gene linkage analysis.

The most common abnormal trait that was documented was cysts that arise from the ciliary body (inside the eye). These cysts are never painful, do not limit vision, and are therefore of no consequence to the eye or the horse. A syndrome of multiple developmental eye abnormalities was seen less frequently. Again, horses born with multiple eye anomalies had normal functional vision with rare exception, were never painful, and were never �born with no eyes.�

Results of our research indicate that the trait has a semidominant mode of inheritance, meaning that if a developing embryo has one �abnormal� copy of the gene, the foal will be born with very minor anterior segment abnormalities (cysts, peripheral retinal folds). The importance of a horse being born with cysts is of no consequence to the horse. The importance of cysts in a horse is only related to production of offspring produced by mating a horse with cysts. A foal born from the breeding of a stallion and a mare that both have cysts (both carry one �abnormal� copy) has a 25% chance of inheriting two �abnormal� copies of the gene. When two �abnormal� copies are inherited, the foal will be born with multiple developmental abnormalities inside the eye. Whether born with one or two �abnormal� copies of the gene, the abnormalities are not progressive, meaning an affected horse will not develop more heritable eye abnormalities with age.

Today there are nearly 6000 Rocky Mountain Horses that are registered by the Rocky Mountain Horse Association. I have now personally examined over 1500 Rocky Mountain horses, and collectively over 2500 Rocky Mountain Horses have been examined by veterinary ophthalmologists in the United States and Canada. Approximately 5% of Rocky Mountain Horses that I have examined have two �abnormal� copies of ASD. Only a very small population of affected horses (approximately 30 horses) have problems with vision. All but two horses that I have examined have had normal functional vision. Only two horses were blind. The percentage of blind Rocky Mountain Horses in the general population of Rocky Mountain Horses is actually far less than the percentage of blind Thoroughbreds, Quarterhorses, Saddlebreds, Appaloosas, etc., in each respective population that I have examined.

The author also mentioned that a rarely seen part of the ASD trait is foals �...born with no eyes.� Anophthalmia is the medical term describing a developmental defect characterized by complete absence of the eyes. Anophthalmia has never been described as part of the ASD trait. This condition is exceedingly rare in all animal species. In fact, anophthalmia has never been reported in the horse. Certainly, anophthalmia is not one of the described anomalies of ASD in horses.1-6

ASD is not unique to the Rocky Mountain Horse�it occurs in all breeds I have examined that carry the Silver Dapple gene�most of those that have a chocolate color coat with or without dappling. This includes the Shetland Pony, Miniature breeds, Rocky Mountain, Kentucky Mountain Saddle, Mountain Pleasure, Morgan, Bashkir-Curly, Naraganssett Pacer, and Haflinger. The author�s statement that the disease is most prevalent in the Rocky Mountain Horse breed is probably not accurate. The disease is probably just as prevalent in some of the other aforementioned breeds. It has only been studied extensively in Rocky Mountain Horses because the breed Association recognized it and was proactive to determine whether the abnormality was a severe defect.

Because of exceptional popularity and financial considerations, it is virtually unheard of when a breed Association recognizes a potential trait that may alter the breed�s future�and subsequently financial worth. It is even less common when a breed Association or Registry acknowledges their breed has a potentially heritable problem decides to become proactive, publicly inviting outside investigators to study the suspected disease. A classic example of an equine breed Association that failed to recognize and address a serious (sometimes life-threatening) disease until widespread dissemination of the trait had occurred throughout the breed (HYPP), was mentioned in the previous article. I commend the Rocky Mountain Horse Association for recognizing a minor abnormality in their breed, for taking the initiative to determine its cause, and for their interest and participation in this collaborative study. In doing so, they have established guidelines that select against propagation of undesirable traits within the breed while promoting genetic diversity within the breed. The Rocky Mountain Horse Association should serve as the model against which other breed Associations and Registries that acknowledge a potentially heritable abnormality should be compared.

David T. Ramsey, DVM
Diplomate, American College of Veterinary Ophthalmologists
Assistant Professor

References
1. Ramsey DT, Ewart SE, Render JA, Latimer CA, Cook CS, Schott HC. Anterior Segment Dysgenesis in Rocky Mountain Horses. Proc Am Coll Vet Ophthalmol 1996;27:46-48.

2. Ramsey DT, Ewart SE. Clinical and Genetic Aspects of Anterior Segment Dysgenesis in Rocky Mountain Horses. Proc Rocky Mountain Horse Association 1997.

3. Ramsey DT, Ewart SE, Render JA, Cook CS, Latimer CA. Congenital Ocular Abnormalities of Rocky Mountain Horses. Vet Ophthalmol 1999, in press.

4. Ramsey DT, Hauptman JG, Petersen-Jones, SM. Comparison of Corneal Thickness, Intraocular Pressure, and Corneal Diameter in Rocky Mountain Horses With Cornea Globosa and With Normal Corneas. Am J Vet Res 1999, in press.

5. Ewart SE, Ramsey, DT. The Horse Homolog of Congential Aniridia Conforms to Semidominant Inheritance. Genomics, 1999, in review.

6. Ramsey DT. Ocular Disorders Presumed to be Inherited in Purebred Horses. American College of Veterinary Ophthalmologists Genetics Committee 1998 and/or Data from the Equine Eye Registration Foundation All Breeds Report, College of Veterinary Medicine, Purdue University, 1998.

7. Website: http://www.naturalgait.com" onclick="window.open(this.href);return false;

8. Website: http://rmhforum.com" onclick="window.open(this.href);return false;

9. Website: http://www.host2you.com" onclick="window.open(this.href);return false;

This is a reprint of an article in the Early Summer 1999 issue of Natural Gait News.
[/i]

This was also attributed to Dr. Victoria Jones on this site: http://www.rosebudriverranch.com/ASD.htm" onclick="window.open(this.href);return false;

[i]Evaluation by a board-certified ophthalmologist is recommended due to the small size and subtle nature of some of the ophthalmic lesions. They may be missed unless a critical ophthalmic examination is performed. Integral to a thorough evaluation is specialized diagnostic equipment, including a slit-lamp biomicroscope and indirect ophthalmoscope. The eyes must be examined both before and after pupillary dilation.[/i]

Dr. Ramsey says it much more eloquently than I can. Thanks, Maigray.

Here's a link to a paper by Dr. Ramsey that has a chart at the end with cysts/MCOA by color: http://www.eye-vet.com/silverdapple/pap…" onclick="window.open(this.href);return false;

[quote="Maigray"]In 1996, Michigan State University began a clinical investigative and molecular genetic study of ASD. Aims of our research were to 1) describe the clinical findings in a large cross section of related horses, 2) to determine if heritability was a risk factor for the disease, and 3) to collect DNA from affected and normal horses for future comparisons of pedigree and DNA marker or candidate gene linkage analysis.
[/quote]

So they they ever do anything with it? I mean test that stored DNA for the silver gene once there was a test??

[quote="Monsterpony"]Here's a link to a paper by Dr. Ramsey that has a chart at the end with cysts/MCOA by color: http://www.eye-vet.com/silverdapple/pap…" onclick="window.open(this.href);return false;[/quote]

Yep I've seen that before, one they aren't tested silvers, two it doesn't disprove the founder effect if he was silver. If he's right, his research so far doesn't prove it.

I know Ramsay thinks that ASD(or MCOA or whatever it's called!) is a silver problem and not a RMH problem he's always made that very clear! I agree there hasn't been any real studies in other breeds so then why is he so sure ASD is there just as much? I've read what he wrote, the other breed examples are pretty vague, even the folks that wrote the paper when the silver test came out didn't see much in it? I always wondered why he didn't do more once the silver test came out.

If silver and ASD seriously are always together, ASD must be a real non event and not worth worrying about then?

How would the linkage work if silver and ASD could link? Would ASD always be there when silver is there? Would it just be a separate gene that sometimes links and when it does it's passed on with the silver? It would be possible to breed silvers that didn't have ASD?

Just wondering how it would work.
Cheers

Danni

[quote="Danni"]
How would the linkage work if silver and ASD could link? Would ASD always be there when silver is there? Would it just be a separate gene that sometimes links and when it does it's passed on with the silver? It would be possible to breed silvers that didn't have ASD?[/quote]
It would depend on how closely they were linked. KIT and Extension are linked fairly close and I believe about 93% of the time they pass together. The other 7%ish amount of time theres a crossover where they pass with the opposite gene.

This chart of a tobi stallions progeny is a good example of it. His "E" is connected with the KIT that has Tobi on it, and his "e" is connected to the part that doesn't have tobi on it.

The black bar is black based horses and the red bar is red based horses.
The solid parts are solid horses.
The striped parts are tobiano horses
The checkered parts are "overo"
[img]http://i627.photobucket.com/albums/tt35…]

The linkage would work very similar to that. The only difference would be how close they are linked. If they are linked closer than KIT and Extension then the percentage that they would pass together would be closer to maybe say 95% if they are linked further than it my be close to say 90%.

[quote="Danni"]
So they they ever do anything with it? I mean test that stored DNA for the silver gene once there was a test?? [/quote]
I actually just emailed Dr. Ramsey with that question (and several others :D). I'll let you know when I do.

[quote="Danni"]If silver and ASD seriously are always together, ASD must be a real non event and not worth worrying about then? [/quote]
I would classify it more as something to keep in the back of your mind particularly if you end up with a horse that seems to have vision impairment. Unless the lens are severely subluxated or the retina is detached, you probably wouldn't even notice a difference in a horse with MCOA except for the few anomalies that are seen with the naked eye though they don't affect vision (megalocornea, iris defects). Most of the other anomlies take some trained in ophthamology to identify; vets have to take a course in recognizing it to be able to call a KMH "ASD clear" through the KMH registry.

[quote="Danni"]How would the linkage work if silver and ASD could link? Would ASD always be there when silver is there? Would it just be a separate gene that sometimes links and when it does it's passed on with the silver? It would be possible to breed silvers that didn't have ASD? [/quote]
There are some silver RMHs that are reported to be non-cyst and some non-silvers (by apparence at least- paper was before the silver test came out) that have cysts so it would seem that they are not 100% linked.

So, sorry we are going off topic now, but, what about Silver in Minis??
Has it just not been there long enough (around 30 years now) for the full effect to be known??
I know there are H/Z Silver Minis (sorry, can't remember one off the top of my head) and I know of only one case of ASD in a Mini....maybe just not diagnosed???
Not sure on this one but, as a breeder of Silver specifically, I shall (no pun intended0 keep an eye on developments.

So, MP, have there been Silver horses pronounced ASD clear, and how do I get my Vet involved in diagnosing them??
If there truly is no way round this I should have to seriously consider dropping the colour from my program......

I wonder if its the same mini we are thinking of with ASD Fizz? This one was imported.

[quote="rabbitsfizz"]If there truly is no way round this I should have to seriously consider dropping the colour from my program......[/quote]

Well this is what I have wondered too, so I look up all the reports, keep an eye on all silvers I know and see. So far I just can't see anything in it, so I'm still breeding silvers. Still planning on breeding silvers, including homozygous ones if that happens along the way.

I personally choose not to have any frame overo in any of my horses, as it's a known homozygous problem. If homozygous silvers are a problem too then I shouldn't really be breeding them. But unlike frame I know dozens of silver minis, including the odd homozygous ones. Including my own pony. None of them have anything obvious wrong with their eyes??

There just isn't any real study on ASD and silver yet so I can't real take on what Ramsay says as yet. An odd random silver in a few other breeds with ASD like cysts in their eyes isn't really conclusive?? I mean their would be hundreds and hundreds of silver minis and Ramsay found one or two with something a bit like ASD??

Sorry if I sound a bit defensive, I'm trying not to be! :D But if I really thought there was an issue here I'd forget about the silvers, I just can't see it yet! I wish someone would do a proper study! Or better yet find the gene for ASD!!

Oh and thanks RiddleMeThis!! I think I need to get my head around the tobiano extension linkage to understand linkage better :?

What happens with the coloured/gypsy cobs? They are mostly black based tobianos, often when a red based foal is born to two black and whites it's a solid chestnut, not tobiano. Not that there aren't red and whites in them, but they aren't really common. Solid blacks appear too of course. Or do you just mean tobiano can link to extension on either black or red?? Actually I just re-read what you wrote, that is what you are saying, as that example is linked to black. But it can also link to red I assume? If I have a black and white tobiano, that carries a red gene, the tobiano could be linked to either the red or the black?? If it was linked to the red, which it must be to have the odd red and white foal? Then the black and white foals must carry red too?? So I wouldn't get a homozygous black tobi foal?? Yes I still need to get my head around this!!
Cheers

Danni

OK, this is really thinking out loud to try and get my head round it so RMT, correct me is I have it wrong.......
If a horse is a B&W then the colour, Black, is attached to the pinto extension, thus it's offspring that are pinto, will be Black based.
As with Roan??
Which I understand a bit better.....
So any Red offspring will be solid.
If a horse is Red and White then the pinto extension is attached to Red and thus all pinto offspring will be Red based.
And all Black offspring will be solid...
Is this right?? :sign

[quote="rabbitsfizz"]OK, this is really thinking out loud to try and get my head round it so RMT, correct me is I have it wrong.......
If a horse is a B&W then the colour, Black, is attached to the pinto extension, thus it's offspring that are pinto, will be Black based.
As with Roan??
Which I understand a bit better.....
So any Red offspring will be solid.
If a horse is Red and White then the pinto extension is attached to Red and thus all pinto offspring will be Red based.
And all Black offspring will be solid...
Is this right?? :sign[/quote]
I'm going to answer your questions first and I believe that it should answer some of Dannis questions as well.

KIT can be attached to either Extension in a Black based horse. The example posted just happened to have it connect to his "E", and its easier to see the linkage when its connected to "E" rather than "e".

So, if a horse is EeTOto and the TO is connected to "E" when bred to a chestnut, all (mostly all a small percentage I believe 7% or so) of his black based horses will be tobiano and all of the red based horses will be solid. When a horse is EeTOto and the TO is connected to "e" and is bred to a chestnut, the opposite will occur, and the Black based offspring will be solid and the Red based will be tobiano.

You can assume some times based on pedigree and progeny which is connected to which. For example, most Warmbloods have "E" connected to their "TO."

It works the same way with any KIT mutation such as Roan, Sabino 1 and the Dominant Whites.

[quote]But it can also link to red I assume?[/quote] Yes it can, but not usually in the same horse. If its connected to Black in the horse it's connected to black and you will only very rarely get it connected to red. If it's connected to red, you will only very rarely get it connected to black. [quote]If I have a black and white tobiano, that carries a red gene, the tobiano could be linked to either the red or the black?? [/quote] Yes. [quote]If it was linked to the red, which it must be to have the odd red and white foal? Then the black and white foals must carry red too?? So I wouldn't get a homozygous black tobi foal?? Yes I still need to get my head around this!!
Cheers[/quote] If tobiano was linked to red, you would most likely NOT get a foal who is homozygous black and also tobiano, unless of course the dam also carries tobiano. There is a small percentage of whats called "Crossover" where the linkage switches, but that is a very small percentage, so small it is barely worth noting. This crossover is also why you wouldn't necessarily need it to be connected to red to get a red tobiano foal.

Does that make a bit more sense for the both of you?

Just a visual example of a crossover for you all using dominant white:

Puchi Trap (heterozygous black) has produced 4 black based and 2 red based offspring. All have been by the cremello stallion Guaranteed Gold. She is known to be dominant white (she is be the tested DW stallion Puchilingui, whose DW was attached to his 'E') and with her DW attached to her 'E'. It is believed that all four of her black based foals are dominant white (as they should be). Here are two for examples:

[img]http://www.angelfire.com/on3/TrueColour…]

[img]http://www.angelfire.com/on3/TrueColour…]

One of her red based foals is solid (and I mean entirely solid, not a single white hair on her)... as she should be given the linkage.

The other red based foal, on the other hand, was a crossover. It is apparent because he is clearly DW and clearly red based:

[img]http://www.angelfire.com/on3/TrueColour…]

Now that the crossover has happened in him, the DW will stay with the red in his line forever except if/when it crosses over again. Since he is red based he will always pass an 'e' to all of his offspring regardless so it has less apparent impact to say the DW is linked to the 'e' in his case. However, three generations down the line if there is a heterozygous black DW tracing to him, you can be fairly certain that horse's DW is attached to it's 'e'.

HTH

[quote="Danni"][quote="rabbitsfizz"]If there truly is no way round this I should have to seriously consider dropping the colour from my program......[/quote]

Well this is what I have wondered too, so I look up all the reports, keep an eye on all silvers I know and see. So far I just can't see anything in it, so I'm still breeding silvers. Still planning on breeding silvers, including homozygous ones if that happens along the way.

I personally choose not to have any frame overo in any of my horses, as it's a known homozygous problem. If homozygous silvers are a problem too then I shouldn't really be breeding them. But unlike frame I know dozens of silver minis, including the odd homozygous ones. Including my own pony. None of them have anything obvious wrong with their eyes??

There just isn't any real study on ASD and silver yet so I can't real take on what Ramsay says as yet. An odd random silver in a few other breeds with ASD like cysts in their eyes isn't really conclusive?? I mean their would be hundreds and hundreds of silver minis and Ramsay found one or two with something a bit like ASD??

Sorry if I sound a bit defensive, I'm trying not to be! :D But if I really thought there was an issue here I'd forget about the silvers, I just can't see it yet! I wish someone would do a proper study! Or better yet find the gene for ASD!!
[/quote]
Danni- I don't see you being defensive. If I were breeding horses that may possibly link to a genetic condition, I would be digging for more info and the important facts. A paper published in 2008 showed that MCOA maps to the same region the silver mutations and those were the only mutations that postively correlated to MCOA. I just reread a passage in the paper that said one reason they hadn't identified that it was the same mutation was because of lack of evidence in the Icelandic horses that are silver. But now that they have confirmed the presence of MCOA in a homozygous silver Icelandic, who knows what will be determined. That being said, PMEL17 (where silver is located) is a 4.9 megabase region and they haven't isolated the whole thing.

I wouldn't lump MCOA together with LWO. With LWO, all homozygous foals die *period*. With silver, homozygous MCOA is definitely not lethal and only a fraction of them even have visual deficits. There is also the small risk of getting a deaf horse when breeding for splashed white. Heck, 80% of grey horses have cancer by their late teens and 100% of homozygous appaloosas are blind at night.

Rabbit- In order to check your horses for MCOA, you would need a veterinary ophthmologist with good equipment to examine your horses' eyes. That being said, this syndrome has incomplete penetrance. That means that there is a wide range of the expression including horses that are completely "clear" of cysts or MCOA including known heterozygotes (one homozygous parent).

[quote="RiddleMeThis"]Does that make a bit more sense for the both of you?[/quote]

Yep! Much clearer now, thank you!

Not sure how it's going to relate to silver and the eye thing if they are linked but I guess I'll worry about working that out when it comes to it! :lol:

Thanks too Monsterpony, I guess I'll just keep an eye on any new developments!!

I thought Puchilingui died before the DW test came out??

OK, I have the Royal Veterinary College just up the road, and my Vets are all in practice there, where do I need to direct them to get them on board testing for this?? (ASD)

I would check to see if they have a boarded ophthamologist at the hospital. They do have a small animal ophthamologist according to the website (at Queen Mother Hospital for Animals) who should be able to examine a horse as you have to study large and small to get your board certification (and mammals are mammals whether they are cat, horse or human). If no one there is knowledgeable about the condition, I would direct them to Dr. David Ramsey, who is the expert in the field and has done most the research. He has a couple really good websites with images of the different anomlies seen. As a vet school, they should at least have the necessary equipment that the average general practitioner does not usually carry.

Here's the link to the ophthamologist: http://www.rvc.ac.uk/Staff/pbedford.cfm" onclick="window.open(this.href);return false; It says he has special interest in inherited disease so he might be interested in examining your horses (I almost typed ponies...whoops!).

[quote="rabbitsfizz"]I thought Puchilingui died before the DW test came out??[/quote]
He did, but I believe they tracked so many of his offspring who had the exact same Dominant White mutation that the only plausible explanation is that he was a carrier as well. Similar to Impressive and HYPP.

Ah, I see. Thanks for that it was puzzling me!

We do that a lot in these types of studies...for example, I know for almost certain that particular Arabians were carriers of CA even though they're dead now simply by tracking the pedigrees of affected foals. And that's not even a trait you can SEE. ;)

The miniature I saw with it - was very obvious - you could see the eyes were the wrong shape and they stood out.