The Mares in Great Sires

Understanding pedigrees, inbreeding, dosage, etc.

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brogers
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Re: X chromosome

Postby brogers » Thu Oct 20, 2011 12:06 pm

stancaris wrote:brogers:

1) you said there are variants on the X chromosome that relate to elite performance. It seems to me that this supports the idea of superior broodmaresof sires like Buckpasser, Dr. Fager, hoist the flag etc. These stallions were famous for getting super daughters who in turn got great runners both sons and daughters. Main point... The x chromosome is vital to the overall success of racehorses.


Yes there are variants on the X chromosome that relate to elite performance

But they are far from "vital to the overall success of racehorses"

We have identified 37 SNP variants across 19 sites on the genome that separate out elite performance from non elite. The variant that reached statistical significance (P value) on the X chromosome is one of these 37 SNP's.

The problem is that when you rank them for relevance, the SNP on the X chromosome is not in the top 10 as far as importance is concerned. There are significantly more important SNP's in terms of performance, that are located on other chromosomes. You are over-rating the variant on the X Chromosome.
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stancaris
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X chromosome

Postby stancaris » Thu Oct 20, 2011 12:11 pm

brogers

You said that Haun has done more to mislead breeders with her x factor theory than any other theory in history. How can you make such a negative statement about her theory when in fact it has not been proven wrong. Do you have any evidence to support such a claim?

You also said that if the X factor was so important for performance then stallions would not have good colts because they only pass on the y chromosome. Not true... Stallions also pass on 32 other chromosomes in addition to the y. Furthermore a colt can get a super x chromosome from his dam along with high quality autosomes from his sire

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Postby brogers » Thu Oct 20, 2011 12:11 pm

DDT wrote:brogers

What you say in your post in number 2 plays right to the theory, the sons of a stallion get one X from their dam, and if there are any genes that help produce superior runners attached to the X they will be expressed in the sons because the Y has nothing to offer other than a sex determination.

DDT


That would require that all of the mares that produced superior colts by the stallion would need to have these genes and have it in double copy (homozygous) so that they had to pass it on. A stretch perhaps?

As I said in an earlier post, there are certainly variants on the X that are related to elite performance but they don't correlate to heart data and they are not as important in terms of influence as other variants located in other genes on other chromosomes.
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Re: X chromosome

Postby brogers » Thu Oct 20, 2011 12:43 pm

stancaris wrote:brogers

You said that Haun has done more to mislead breeders with her x factor theory than any other theory in history. How can you make such a negative statement about her theory when in fact it has not been proven wrong. Do you have any evidence to support such a claim?

You also said that if the X factor was so important for performance then stallions would not have good colts because they only pass on the y chromosome. Not true... Stallions also pass on 32 other chromosomes in addition to the y. Furthermore a colt can get a super x chromosome from his dam along with high quality autosomes from his sire


Stan,

Try to remember that the onus should be on her as she never proved it to be a solid theory in the first place!

1) Thoroughbreds have, as a breed, larger hearts in proportion to their body weight than other less athletic breeds. The size of the heart has responded to selection for athleticism in general.

2) On present knowledge, there is unlikely to be one single factor that can identify the elite thoroughbred, and that includes heart size. It is going to be a multitude of factors. There are several very well known champion racehorses that have hearts that are smaller than average, and a lot of horses with very large hearts that cannot get out of their own way.

3) Her theory relies on a single mutation within a gene on the X Chromosome controlling heart size. If it was a single mutation having such a major effect on racing performance then it can only follow that we would have likely selected for it and at this stage, after 300 years of breeding, that all horses would have this mutation. A horse being Grey is controlled by a single mutation on a gene. If being Grey meant that you had superior racing ability, it would only take two or three generations for breeders to select out all the other horses to make sure that all horses were Grey. Same with hearts.

4) The expression of X chromosome genes is very complicated. Inheritance of the X Chromosome is straight forward, but the expression of the genes on the X is not as the process of X-inactivation takes place (the method to make sure that for most of the genes on the X chromosome there is an equivalent expression in males and females). The best example of this is the Tortoiseshell Cat. The mutation producing red coat color is in a gene located on the X chromosome. Males that have the mutation have a solid red color (as they got the X from their mother), as do females who are homozygous (both copies) for the mutation. Females who are heterozygous (one copy with the mutation, one without) have a combination of red and black coats. Just because they have a copy of the mutation, doesn't mean they will express it.

Now with that all said, what evidence do I have that she is wrong?

We have sequenced some 500 horses and have cardio data on some 4000 horses. The fact is that horses that have 'elite' hearts (those that are the right size with the right wall thickness) as well as 'elite' spleens (a vitally important part that Haun missed), do not necessarily share the variants for elite performance that we found on the X Chromosome. Some of the elite horses have the variants, some don't. Identifying elite performance is significantly more complex than Haun has led people to believe in her books.
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stancaris
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X factor

Postby stancaris » Thu Oct 20, 2011 1:29 pm

Brogers

When you say that you sequenced 500 horses does that mean your researches have sequenced all the DNA codes on the X chromosome of these elite hearted thoroughbreds?

If so I see your point. If not, you really do not know about all the genes on the X and therefore Cannot be sure that a single heart gene does or does not exist ( simply because your research teams have not yet found it).

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Postby DDT » Thu Oct 20, 2011 1:49 pm

brogers

I do not care to bicker with you about this, but it is still a theory and you offer no scientific facts to disprove it, just opinions. I personally could care less whether anyone believes the theory or not, something is going on with the X chromosome and yes, every elite colt produced receives an X from his dam and most if not all of those genes on that X have a chance at expression without help from the Y. A lot of breeding theory is a stretch, you are in the nicking business and now the genetic marker/prediction business. You certainly did not involve yourself with these types of businesses without the thought of making a profit, whether or not your predictions came true. If you thought otherwise you would refund clients money every time the results were less than expected. I believe your bias overcomes your logic when it comes to any matter that might cast a shadow on what you do for a living. The one thing in this business that remains constant is there is always someone out there telling people they have the answers when it comes to breeding superior horses and will sell it to them for the right price.

One of the most important factors that is seldom talked about when discussing the X Factor is that just because a horse has a larger than normal heart does not mean the horse will be an elite race horse. The pump could be massive, but if the legs don't move that fast, or the lungs cannot deliver enough fresh oxygen, or the attitude is not right, the horse may just be an also ran. So, even if this theory is correct in some manner, it still is not the sole reason behind the superior runner.

DDT

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Re: X factor

Postby brogers » Thu Oct 20, 2011 2:17 pm

stancaris wrote:Brogers

When you say that you sequenced 500 horses does that mean your researches have sequenced all the DNA codes on the X chromosome of these elite hearted thoroughbreds?

If so I see your point. If not, you really do not know about all the genes on the X and therefore Cannot be sure that a single heart gene does or does not exist ( simply because your research teams have not yet found it).


On our data, using the 75KSNP chip, when you looked at the DNA of horses with large/effective hearts and compared them to horses with small/non-effective hearts, we couldn't find a variation/mutation in genes specifically on the X Chromosome. As far as we could see, there does not seem to be a single X chromosome gene that controls cardiac size/function as discussed in Haun's books. There are variations that are found in large/effective hearted horses that are not on the X Chromosome.
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Postby brogers » Thu Oct 20, 2011 2:28 pm

DDT wrote: I personally could care less whether anyone believes the theory or not, something is going on with the X chromosome


I have actually agreed with you on this point all along. There is something going on with the X Chromosome in relation to superior runners. Without a doubt. It just hasn't got anything to do with heart size/function which is what the X-Factor book suggests. There are stallions that generally get a particular heart type which tells you that heart morphology doesn't travel on the X.

DDT wrote: One of the most important factors that is seldom talked about when discussing the X Factor is that just because a horse has a larger than normal heart does not mean the horse will be an elite race horse. The pump could be massive, but if the legs don't move that fast, or the lungs cannot deliver enough fresh oxygen, or the attitude is not right, the horse may just be an also ran. So, even if this theory is correct in some manner, it still is not the sole reason behind the superior runner.


Again, I agree with you here. There are a multitude of reasons why a horse is a good horse and it seems to be that the best horses have enough of these working in harmony to make it all work. Even within genetics, it is not one gene, but many that are at work (polygenic profile).
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X factor

Postby stancaris » Thu Oct 20, 2011 4:10 pm

brogers

Just because you have not found a gene on the X for heart size, does not mean there are none present on the x that govern heart size.

You have also not answered my question yet... Did your researchers sequence all the DNA codes present on a horses x chromosome? If not, you cannot be sure that Haun's theory is right or wrong and there may just be a gene on the X that dictates a large heart.

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Postby Tappiano » Thu Oct 20, 2011 5:30 pm

Regardless of the size of the heart or size of the spleen if a horse looks like a giraffe it will not be an efficient runner.

I guess a more fundamental question is whether there are any traits on a thoroughbred that are passed on and modified, ie, short and long = medium. There was a discussion that you either get lots of leg/bone or not but not something in between and maybe you get long backed or short backed but you are not going to get medium. Does anyone know whether the matriarchs throw foals that are consistently like her? If not, are there any specific traits that they had in common?

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Postby xfactor fan » Fri Oct 21, 2011 1:36 am

I've been staring at conformation photos for years now and have come to believe hind end conformation is not sex linkedl, and forehand conformation is X linked, or pseudo X linked. (in this context, pseudo X linked could be a regular chromosome but only is active if passed on from the female parent)

Don't know about the ears, but from the poll down the neck, withers, shape of the ribcage and shoulder seem to travel together as a unit. I'm unsure about the forearm, but from the knees down is likely to also be on one of the autosomal chromosomes.

Take a look at Ashado

http://www.sporthorse-data.com/d?i=10553270

and her son Star Cat

http://www.sporthorse-data.com/d?i=10593283


Curlin

http://www.sporthorse-data.com/d?showpi ... 1312707062

Deputy Minister
http://www.sporthorse-data.com/d?i=10005440


And just for the record, I didn't wake up one morning and decide that this was the one true way.

Along the way I've looked at sires and sons, mares and their sons, equine hybrids (real ones, now what some folks describe as hybrids) different breeds of horses, breeds that may have contributed to the foundation of the TB, and big cat hybrids.

If anyone is interested I can lay out the theory, and you guys can test the theory against your own experience.

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Re: X factor

Postby brogers » Fri Oct 21, 2011 5:03 am

stancaris wrote:brogers

Just because you have not found a gene on the X for heart size, does not mean there are none present on the x that govern heart size.

You have also not answered my question yet... Did your researchers sequence all the DNA codes present on a horses x chromosome? If not, you cannot be sure that Haun's theory is right or wrong and there may just be a gene on the X that dictates a large heart.


Stancaris,

We didn't find a gene that regulates heart size on the X Chromosome. I spoke to Dr Matthew Binns, formerly of the Royal Veterinary College in England and now from the Genetic Edge and Dr Emmeline Hill of the University of Dublin and Equinome at the recent Genetics and Pedigree Conference and neither of them have found a gene on the X related to heart size. Both were dismissive of the X Factor based on their own research.

People have invested a lot of money, time and mental effort in this theory, including Ms Haun, but breeding and selecting for elite performance is significantly more complex than indicated in her books.

Genomics is only just starting in this industry, but in time it will replace theories like the X Factor, Nicking, Rasmussen factor and the like with more scientifically factual events such as QTL's and Polygenic Profiles. Even then there will be epistatic events that will influence the outcome, and then we will still be at the mercy of the environment (trainers, etc), but rather than guessing if your foal got what you want it to have, you will know, and rather than guessing if the stallion will suit the mare, you will have a scientific basis for your decision.
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X factor

Postby stancaris » Fri Oct 21, 2011 11:22 am

Brogers:

American Turf Monthly just published an article of mine that deals with the X factor and this article appears in the Nov 20011 issue of the magazine and is entitled 4 Major Heartlines Point Out BC Classic Winners

In that article I stated that 70% of the last 20 BC Classic winners have a broodmare sire that carries at least one of the 4 big hearted stallions identified by Haun (Princequillo, War Admiral, Mahmoud or Blue Larkspur) in the X passing position. Supporting evidence for the inheritence of the X chromosome can also be found in major Grade 1 races at 10 furlongs. I researched the last 20 runnings of the Jockey Club Gold Cup, the Hollywood Gold Cup and the Suburban Handicap and found that more than 70% of the winners of these demanding route races also had a broodmare sire that carried one of the above 4 major heartline stallions in the X passing position. Winners of other major route races run in this country will also have a high percentage of the above 4 major stallions being found in the X passing position of their broodmare sires.

Further support for the X factor theory is found among the last 20 Derby winners. Since 1992 there have been 17 Kentucky Derby winners that carried one of the above 4 major stallions in the X passing position either from their broodmare sire (12 winners) or from their second damsire (5 winners). That's 85% Derby winners with a heartline to one of the above 4 stallions either from the broodmare sire or the second damsire.

Further support can also be found among Horses of the Year where a very high percentage of these elite horses usually carry one of the above 4 major stallions in the X passing position.

Support for the X factor theory also comes from noted breeders: Penny Chenery (owner-breeder of Secretariat) who said, "The X factor sheds light on previously inexplicable performance in the breeding shed of some of history's greatest champions.

Pope McLean of Crestwood Farms states that the X factor theory can genetically explain why some nicks are so much more successful than others.

John C Harris California Owner and Breeder states that Hauns X factor book will prove a valuable aid to breeding better horses.

Edward L Bowen, President Grayson Jockey Club Research Center states, " Marianna Haun and the scientists she worked with have articulated another piece of the puzzle of genetics which can be used towards producing a better animal."

Dr. Thomas Swerczek-University of Kentucky Gluck Equine Research Center states, " With what we are finding out about the large heart passing from sire to daughter, this helps explain the broodmare sire phenomenon."

Frank Mitchell, Ph.D. author of Racehorse Breeding Theories published in 2004 devotes 22 pages of the above book to the X factor theory. His reference to the X factor theory is clearly one of acceptance and not dismissal.

The above are some very well respected people and they embrace the X factor theory of Haun.

So far there has not been any evidence to show the theory to be wrong. Just because a gene has not yet been found on the X chromosome for the production of a large heart does not mean that such a gene does not exist.

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Postby Pan Zareta » Fri Oct 21, 2011 9:55 pm

brogers wrote:We have sequenced over 500 racehorse now, both elite and non-elite and three things are clear...1) There are variants on the X Chromosome that relate to elite performance....2) These variants do not correlate to heart size...and 3) The X chromosome variants are not as important as many of the variants found on other chromosomes, in particular ECA18 that relate to muscle type.


Did you look for correlation between variants on the X and large hearts irrespective of performance? Even when all other organs/organ systems are equal, size is not the sole mediator of cardiac output and performance, at least not as I understand it. How can one be certain that screening for elite variants will pick up all variants related to heart size?

stancaris wrote:70% of the last 20 BC Classic winners have a broodmare sire that carries at least one of the 4 big hearted stallions identified by Haun (Princequillo, War Admiral, Mahmoud or Blue Larkspur) in the X passing position


What percentage of the overall TB population has a broodmare sire with one or more of those stallions in an X passing position?

stancaris wrote:The above are some very well respected people and they embrace the X factor theory of Haun.


Most of those statements are from the back of Haun's first X Factor book, publshed 1997, light years ago in terms of developments in molecular genetics, and the remarks should be regarded in that context. Fwiw, I know and have the utmost respect for Marianna Haun. She put together a meticulously researched, circumstantial case for the theory that equine heart size is a simple, sex-linked trait. I'm not sure it can be absolutely ruled out that something on the X is mitigating heart size, but am quite confident that inheritance of a heart of superior size and performance isn't nearly as simple as many thought it might be 15 years ago.

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Postby xfactor fan » Sat Oct 22, 2011 2:18 am

Large hearts and one single gene may not be the correct model. What we know is that there is a large amount of size variation in equine TB hearts.

Whatever controls heart size (healthy normal hearts) may be a region, not a single gene. Think of human eye color, not a single gene like equine gray coats.

Or the gene (s) for heart development may be on one of the other chromosomes, while there is a gene or genes that regulate size on the X. There's got to be some mechanism that sets size of organs, otherwise how does a liver know when to stop growing?

PZ makes a good point, just because a horse has a large heart, doesn't make it a good racehorse. How many Secretariat daughters were great racemares? Or Sham's daughters? Or name any other stallion with a known large heart?

My issue with Haun is that her storytelling got in the way of the science, and as a professional writer, her goal is to sell books. She hit the target market, with how she spun the science, reducing a very complex set of genetic issues down to 1 large heart = great racehorse.


stancaris

Great to see you back, always enjoyed your posts.

Have you ever taken a look at the pedigrees of --oh, lets say, bottom level claimers at Turf Paradise, applying the same criteria you have used with Derby fields? If so, what are the results?

Always interesting to see different viewpoints on complex problems.