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Q & A -- Can the 'X-Factor' be Incorporated in TrueNicks Pedigrees?

Dale asks: I am a small breeder in NY, and have a limited barn of mares. I have been fascinated with the X-factor in the breeding process and wonder why the nick reports do not highlight the heart scores of those known. It also would be nice to see if a stud is a single copy and if a mare was a single of double copy. I recently had a race filly die, and her heart was weighed as part of the autopsy. She has also been identified as a double copy mare, along with her dam. So of course, I would like to breed the dam again, but only to a single copy stud.... Any thoughts on how to locate just those that fit my criteria?

 Alan's response: Thank you for the question.

Firstly, TrueNicks is designed to measure one specific element of the pedigree, the affinity between the sire line and the broodmare sire line. Although this is only one pedigree factor, it is one that lends itself to objective measurement, and where there is a measurable and statistically significant relationship between the nick rating and potential racing ability.

We may well broaden the scope of the program to give scores to other pedigree aspects, but I am not sure that the heart scores would be one of these (among other reasons, it may be proprietary information). Personally, I question the absolute validity of the X-factor theory. There does tend to be some relationship between the dam and heart output (rather than simple size -- it is possible to have large heart that is not as efficient as a smaller one), but those who study hearts tell me that they also see trends among sires in this respect.

I think that the hypothesis that there is a single mutated gene on the X-chromosome that significantly and positively determines heart performance and subsequent race performance is a bit of a stretch.

29 Comments:

When a great race mare goes

to the breeding shed, one would like her to reproduce

herself. But great race mares are usually bred to

prepotent and dominant stallions. which may create

somewhat of a genetic conflict. This could be one

reason why many great race mares do not become great producers.

Obmar 12 Sep 2009 1:42 AM

Yes, but do we know if these dominant stallions carry the X for the large heart??

DaleLee 12 Sep 2009 8:31 AM

I am also intrigued by the X factor.  I do believe it has some roll in determining performance.  I also believe it can explain why a race horse who is by a stallion who is known for throwing sprinter milers, when bred to a mare with this "X Factor", all of the sudden throughs a horse who does not even take a deep breath until they have run 1 1/4 miles.  Although Bold Ruler won at 1 1/4 miles, he was no known for throwing stamina.  Somethingroyal was by Princequillo who absolutely ate up 1 1/2 and 2 mile races.  Together they produce a filly known as "The Bride", who could not put one foot down in front of the other.  The next year they produce Secretariat.  Go figure??  While the X Factor is a growing phenomenon, I look at the sires racing ability and his sire line affinity with my mare's dam line and her sire's sire line.  Anything other than that is gravy if the foal turns out to be a runner.

Robert 12 Sep 2009 12:26 PM

Dale, you didn't say if your filly died from being a double copy filly? was her heart too big?

Lassie Dear was a double copy (all winners) and so was her Secretariat daughter, Weekend Surprise (all winners), who produced AP Indy and Summer Squall...who obviously "click" with a number of lines, I wouldn't be surprised in a number of years to find that nicks were actually successful for factors like heart size, etc...I mean it's a genetics game and genetics of the heart are as valid, and more important, than many other factors...there are thousands of horses with great conformation that can't run.

da3hoss 12 Sep 2009 2:31 PM

It's not a stretch in my research. We are having considerable success in breeding specific hearts in individuals and seeing that success come to fruition on the racetrack. We have just foaled out this year our fifth crop of horses and have 100% large hearts. We have duplicated Secretariat's large heart and have physical evidence of the path of his great heart, which is by the way, also found in Rachel Alexandra, Mine That Bird and Summer Bird. The work of the last 16 years will be in my new book coming out next year. We will be racing 70 horses next year with the large hearts that we have bred into them. We currently have 40 in training. Marianna Haun

Marianna Haun 12 Sep 2009 5:57 PM

Dale's and Obmar's remarks are suitable examples for why a little bit of knowledge can often be worse than none at all. A "large" heart is often a hypertrophied heart secondary to CHF. I suppose a proper autopsy can differentiate those hypertrophied ( a negative) from those with larger chambers (a positive). As far as Obmar's comment; what is the genetic/scientific basis to your reasoning?

sceptre 12 Sep 2009 8:00 PM

Marianna, do you have a barn name or web site to follow your horses? I am fascinated by the X factor, I can't seem to find any of your books that are not extremely expensive, but I am looking forward to your new book. I would like to "follow" your racehorses if there is a way.....

LyndaP31 13 Sep 2009 7:22 PM

Just as a broodmare sire can exert great influence on the breeding capabilities of his daughters, one can assume, as did Tesio, that a mare can spread her genetic influence through her sons. According to the dosage theory of Franco Varola, “Enduring male lines are founded or transmitted by brilliant stallions. Conversely, elite broodmare sires are devoid of brilliant blood. Brilliant blood is the influence of extreme speed generated by 18 stallions foaled since 1900. These brilliant stallions earned only moderate success as broodmare sires. Of these 18 brilliant sires five trace to the great producer Lady Josephine.”

Obmar 14 Sep 2009 12:31 AM

The validity of Marianna's research has been proven by studies in Australia and Great Britain and applies to other breeds of horses as well. It is important to separate "ENLARGED" heart [unhealthy] with the X-Factor large heart, which serves as a large engine. As I understand it, just because a horse has a large heart doesn't mean it's automatically game - it has to want to perform, but the large heart is there to work if the horse wants to or can be persuaded. If you read Marianna's books on the subject, the genetic/scientific basis is extensively documented. Her co-authors were Fred Fregin, DVM [cardiac specialist]and Gus Cothran, DVM [genetic specialist], both of whose credentials are well known.

Cynthia Hecht 14 Sep 2009 10:36 AM

In response to Lynda: Our first crop from our stallion Maverick, a son of Dixieland Band out of Bonnie's Poker, who is a half-brother to Silver Charm are hitting the track this year. The two-year-olds are showing great promise. He has a son out of Miss Lady Di by Dehere who is out of Patchiano, a half-sister to Broad Brush. He is burning up the track and should make his debut in a few weeks. His name is Royal Hay Patch and he is expressing Dehere's heart. His daughter, Gran Senora, has hit the board in both of her starts running at a distance which is a little short for a two-turn horse. We have about 32 of his first crop in training with 30+ yearlings coming next year. We also have a number of horses by Kentucky stallions who came in utero in the mares purchased at Keeneland. Marianna Haun

Marianna Haun 14 Sep 2009 4:53 PM

Marianna; Thank you! I put him in my DRF.

LyndaP31 15 Sep 2009 11:57 AM

I have to question the validity of the responder, when he shows no education in studying genetics. His final comment is proof of that.

The X-factor isn't about performance. It's about the ability of breeding a recessive trait, believed originated in Pocahontas(GB)1837.

Every Double-X mare traces back to her and passes on the dominant-X to her foals. Every stallion, whether he carries an X or an x, that traces his female line back to her, has the ability of passing on her recessive trait to his daughters, even as a through-gate of the dominant-X, when he carries the small-x.

As proof in itself, the great broodmare sires with and without the large heart, have passed on that trait. Northern Dancer is a prime example.

Anyone can research this through pedigreequery.com.

Having a mare, who traces back to Pocahontas, and breeding her to a stallion, who traces back to her, has a good chance of stamping that recessive gene. The more you encourage this breeding, the more likely you are to produce horses with a large heart. That large heart, being twice the size of a normal Thoroughbred's, can pump twice the volume of oxygen rich blood. Horses, like Secretariat and Phar Lap, had that big engine and could run all day long.

Anyone with basic knowledge of Genetics 101 knows this. It's not rocket science.

It doesn't always translate to winning on the track, but mares, like Weekend Surprise, was not only a proven XX racemare, she stamped her foals.

In her case, she received a dominant X from both Lassie Dear and Secretariat.

Find the Blue Hen mares, through a website like bloodlines.net, and research their lineage.

It's hard to know how  Glencoe/Marpessa produced a freak, but if you look at their female lines, there's a pattern to the foundation mares of American Thoroughbreds.

There's also plenty of her recessive bloodlines to find the right match. I'll even go as far as to say Zenyatta and Rachel Alexandra probably have a large heart. They have a deep girth, their scopy, and they run effortlessly.

Ed Schreiner-EDON Equine 15 Sep 2009 1:02 PM

Marianna...How can we tell if our mare carries this gene.  My mare is by Fly So Free out of a Tom Rolfe mare that is out of an Alleged mare, that is out of a Buckpasser mare that is out of Northern Dancers full sister Arctic Dancer.  I hope that is not to much.  Thanks and I look forward to your new book.  Oh by the way, the mare is in foal to Quiet American for 2010.

ROBERT 15 Sep 2009 2:44 PM

In reply to Robert, with those bloodlines, you can be pretty sure your mare has a large heart and will pass it on. Without her name I can't guarantee it because most pedigrees have genetic holes in terms of large hearts because of the pattern of breeding distance to speed. But the odds are on your side. Quiet American passes a large heart on his X which he gives to his daughters. In our research about Secretariat's heart, we have found a line even larger than the Eclipse line. This is the X line to the Darley Arabian. That is the heart that Secretariat is expressing as well as Rachel Alexandra and some of history's greatest runners including Man 'o War, Lexington, Phar Lap, St. Simon and Hyperion. We have found exciting physical proof of this line which I will discuss in my new book. It explains more than just the engines of these amazing athletes. Good luck with your upcoming foal. Marianna Haun

Marianna Haun 15 Sep 2009 3:42 PM

Robert,

Fly So Free's Dam has Pocahontas on her top and bottom.

Tom Rolfe is by Pocahontas(USA)'55, who carries the line through Roman and How.

Whether it's Tom Rolfe's grandson Alleged or the '59(GB), they both carry on the X through their female line.

Arctic Dancer gets the X through both lines, with Natalma passing it on through both Stockwell and St. Simon, passing on through Sire and Dam.

Buckpasser's Dam - Busanda, gets the X from War Admiral(top), Blue Larkspur and Latroiene(bottom) and most likely carried the Dominant double X with copies from all three female lines.

Quiet American's Dam, Demure, could have been a Dominant double-X, with multiple lines tracing to Pocahontas(GB)'1837.

Ed Schreiner-EDON Equine 15 Sep 2009 4:57 PM

Dear Edon,

The female half of any pedigree contributes two X chromosomes to the male's single X chromosome which is inherited from his dam line only. The female half of a pedigree contributes more genetic material especially mRNA, the santum santorum of genetic transmission, than the male y chromosome.   All good stallions require good mothers.   Broodmare sirelines are a case in point as well. Broodmare sires carry the dominant X chomosome. Nature takes care of imbalances from breeding and racing performance within three generations which is partly why, and rightly so, linebreeding and inbreeding need periodic reinformance within pedigrees. Distribution of genetic traits is not a 50/50 - male /female proposition.

If your wanting to learn more about 21st century genetics, I suggest you read the following excellent books: They will get you past 101 and 102

1.) Ridley, Mark. (2001) "The Cooperative Gene - How Mendel's Demon Explains the Evolution of Complex Beings" Simon & Schuster. (This guy is excellent, from the Department of Zoology at Oxford - new concepts in Chapter 8)

2.) Gould, Stephen J. (2002) "The Structure of Evolutionary Theory" Harvard University Press (This book covers everything from Sewal Wright's Shifting Balance Theory, genetic drift, adaptative topographical landscapes, punctuated equilibrium, and speciation)

3.) Zimmer, Carl (2001) "Evolution: The Triumph of an Idea" (PBS Series) (Good general introduction book)

Please let me know if I can assist you with some further reading.

Obmar 16 Sep 2009 4:55 AM

Reply to Obmar,

I'm not sure of your referencing. Nothing I stated is a misrepresentation of genetics factors.

Anyone, who is serious about the genetics of their stock, will test, before they take a course of action to perpetuate a desired trait. I've been actively involved in a breeding program for 47 years. I've also had proper genetics schooling in animal husbandry.

Maybe you've misread my comments. Sexing strategies to produce the large heart would be best served by finding a mating pair giving you the most ideal patterns.

I didn't go into detail, because  the depth of research goes beyond a comment on a blogging page.

I don't know who you are, but I study genetics daily. When I have questions that need further explanation I speak with my Vet, who's an equine engineer, or I have a conversation with Ron and Ellen Parker.

Ed Schreiner-EDON Equine 16 Sep 2009 10:19 AM

Marianna .....the Mares name is So Fly.  She has had foals by Pur Prize, Alke, Greatness, Omega Code, and Now in foal to Quiet American.  Thanks for your time on this.  I appreciate it.  Robert

ROBERT 16 Sep 2009 12:56 PM

Marianna,

First let me thank you on your insightful work.  

Second, to everyone interested in this topic, let me offer some insights.  Before becoming a horse breeder, I was a W.L. McKnight Research Fellow in molecular biology.  Both as an undergraduate and as a graduate student.  My ill-fated doctorate involved finding the cis-acting DNA binding sites for trans-acting regulatory proteins in a family of genes expressed during late seed development.  During my graduate course work, we studied the fruit fly extensively - they are a great genetic model - they reproduce quickly for one.  Unlike horses obviously.

But for those who think that a mutation in one gene can't make a huge morphological difference, consider two single gene mutations in Drosophila: bithorax and antennapedia (sp?).  With bithorax, a single gene mutation resulted in a complete replication of a functional thorax and wings in the mutant flies. With antennapedia(?), legs and feet appeared where the the flies antenna should have been.

The genes mutated in each case belong to a group of regulatory proteins encoded for by what came to be called HOX genes (HOX for Homeobox containing genes).  These are regulatory proteins that bind to DNA and turn on a "program" of other genes.  Think of the them as "master control genes."  They dictate the elaboration of the entire body of the organism.  And all segmented organisms have these genes, and the DNA sequence of these genes from fruit flies to humans is highly conserved (i.e. close to being identical).

Horses are not often the subjects of molecular developmental studies.  But humans and mice are.  Data from those studies suggests that HOX genes on the X chromosome are involved with cardiovascular development.  Data from mice suggests that females are also genetic chimeras with respect to this HOX gene expression - meaning BOTH HOX genes can be expressed, and thus contribute to the morphology and function of the heart and cardiovascular system.

But, as Tesio notes, horses are genetic hybrids and they inherit each part of their body separately.  This fits in perfectly with my understanding of embryo development in segmented organisms (fruit flies, mice, humans and horses, among many others).

In our research, a "large heart" is necessary but not sufficient to perform at the top of the game, especially past two turns.  Something else is just as critical - the other parts of the horse have to be biomechanically efficient and compatible.  There are horses, even Grade 1 winners, that have the front end of a route horse and the hip of a sprinter (for just one example).  These horses tend to be less than stellar in the breeding shed.  Equix Biomechanics has published quite a bit of work on this.    

Our breeding system is called The Genetic Compatibility Index.  It's goal is to use X-factor insights and our ever growing database of phenotypic analysis of mares and stallions (originally funded by The Kentucky Science and Technology Corporation), to be able to advise clients as to which stallions are expressing the HOX genes that will best compliment their mares.  If you think about a horse's body as being one side of a Rubic's Cube, you want the front, middle and rear segments of the horse to be all the same color!

All Thoroughbreds are genetic hybrids.  And most genetic hybrids - whether you're breeding corn or horses - are "failures."  They are not as good as their best parent.  Throwing in another analogy (sorry), if Thoroughbred genetics is like a deck of cards, with only so many possibilities and outcomes, you want to breed a "straight flush" or "four of a kind," not a mixed up hand of nothing.

We use the GCI for our own breeding program, and wouldn't think of breeding horses without it.  And Marianna, we would be happy to consult with you anytime.

Thanks again, and good luck to all the breeders and owners out there.    

gary at rough creek 17 Sep 2009 1:39 PM

I am thrilled that my question has created so much discussion. In regards to my mare, No she did not have a defective heart- my reference to a large heart should have been clarified that she had the X factor large heart. She died of an infection from the track,  nothing to do with her heart.

When discussing Weekend Surprise and LAssie Dear- Don't forget to mention Gay Missile.

I'm still curious if the "nick" reports can include the X factor in their reports.

DaleLee 17 Sep 2009 8:45 PM

I truely Believe in X-factor and i am involved with a Small Breeder in Wa. that has Bought most mares and bred off X-factor... Please add this..

Brett St. Amand 21 Sep 2009 7:52 PM

Having been away at the Keeneland Sales, I haven't had time to answer the comments here. It seems to have evolved into quite an interesting debate.

Firstly, as far as incorporating the supposed "x-factor" into TrueNicks: TrueNicks is designed to rate a specific pedigree factor, the success of the sire line when crossed with mares from the broodmare sire line. We nay well introduce enhanced TrueNicks pages with other data, but I don't think the x-factor fits with this, when we are dealing with ratings that have an objective measurement.

Regarding my "showing no education in studying genetics.." I would admit that I have no formal qualifications in genetics. However, I've followed the subject of the relationship between heart output and the x-chromosome ever since I was working at Stud & Stable magazine in the early 1970s and we published the work of Prof. Steele in Australia regarding heart output and sex linked inheritance.

I was an invitee to the conference on the Equine Genome at Cold Spring Harbor around 15 years ago, and have had the opportunity to talk to many experts on the subject, including Dr. Cothran, who was quoted extensively in the X-Factor book.

I've also had a number of discussion of the subject with the leading exponents of heart-measurements.

I would certainly concede that some elements of heart function are sex-chromosome related (and in terms of performance, we are really interested in heart function rather than pure size).

However, those that do a lot of heart scanning at sales, also note correlations between stallions and hearts, so I'd still hold that as far as inheritance of a "high-performance" heart we are looking at more than a single gene mutated gene that stems from Pocahontas.

Incidentally, as a runner, and student of exercise physiology, I'd be interested to know if anyone has considered whether some hearts (and for that matter other elements of athletic performance) have a greater potential for adaptability to training than others?

I suspect that there is still an awful lot to discover!

Alan Porter 22 Sep 2009 10:59 PM

Can someone explain to me how a mare is determined to be homozygous or heterozygous? I understand the x and y being passed down but how was it determined initially, especially in the horses well back in the pedigrees? Thanks.

Brent 23 Sep 2009 5:50 AM

Brent,

In the literature on the X-factor and "large" hearts, there is some confusion in the terminology used regarding "dominant" genes, "recessive" genes, and the resulting phenotype of the horse in question.

Different forms of the same genes are called "alleles." They are actually slightly  different DNA sequences for the gene in question.  

With autosomal traits (traits that are determined by genes that are NOT sex-linked), a horse inherits two alleles for that gene...one from each parent.  If they inherit the same "allele" from both parents, then they are homozygous for that gene.  If they inherit different alleles, then they are heterozygous for that gene.

With sex-linked traits, (those on the X or Y chromosomes) males only inherit one copy of those genes (normally)...whether they are X-linked or Y-linked.  Females inherit two X chromosomes (normally), so they can be homozygous or heterozygous for those genes on the X chromosome.

Getting to your question, I believe the assumption that some people make is that, if a mare has a larger than average heart, she must have two "large-hearted" alleles of a mutant gene that encodes - entirely or in part - for large heartedness.  That would mean that she is "homozygous" for large heartedness, but she's not necessarily carrying two copies of the same large hearted allele.

However, this assumes that the large hearted allele(s) are all genetically recessive to the "normal" alleles which cause normal sized hearts, and that if a mare is a heteroygote (normal heart and any other large hearted allele), then the mare will have a normal sized heart.

Patterns of some X-linked genes in female mice suggest that both alleles are expressed, and at different times during development, making those female mice genetic chimeras.

If a strict dominant/recessive expression pattern exists for mares which are heterozygous with respect to the normal heart size alleles and any large hearted alleles, then we should see a biphasic curve with two peaks when a population of mares is measured.  Those that are homozygous for the normal sized heart, and those that are heterozygous with one copy of the normal sized heart allele, should all have normal sized hearts.  Only those with two copies of a large heart allele should have large hearts.  There should be two normal distribution curves: one peaking at the average size for a "normal" heart, and one peaking at the average for a "large" heart.

From data that I've seen from Equix Biomechanics, there appears to be just one normal distribution curve, at least when "Ejection Fractions" are measured.  Whether this refutes the predicted bi-phasic distribution curve idea or not is too early to tell.

However, in my biological education, no natural genetic phenomenon was ever perfectly exact.  There was always a normal distribution about an average value. Therefore, I always had difficulty in accepting Marianna's statements regarding those rather "exact" heart scores and allele origins.    

Having said that, the functional way to determine if a mare is genetically homozygous for large-hearted alleles (they may be different sequences), is to only breed her to large-hearted stallion or stallions and measure all the progeny.  If she's truly carrying two large hearted alleles, all of her progeny should have larger than average hearts.  If she is heteroygous (large/normal), then at least half of the colts should have normal sized hearts.

Hope that helps.

Gary at rough creek 25 Sep 2009 10:54 AM

Thank you Gary. That's exactly what I was unclear about.

Brent 25 Sep 2009 10:36 PM

I'd like to add to my comment.

I think what is going on in this string might be some confusion arising from the term 'large heart'. I know some of the people that do the actual measuring of the yearlings at the sales, etc. and they maintain several points that I think might be obscured here.

For example, size doesn't matter for sprinters. A horse could win at Grade 1 level sprinting and an uninformed breeder might infer that  that animal had a large heart where that might not necessarily be the case. Another example is a large heart with thin walls and low stroke capacity that can be exhausted easily. This type of horse can do well at the elite level unless it is required to make a 'middle move' somewhere in the race, of an 11 second and change nature. But a horse with this heart can run 12 second furlongs all day. This again is different from a thick walled horse with great pumping capacity.

I think the actual benefit of a 'large' heart for racing needs to be more clearly defined. Thanks again to all for an interesting string.

Brent 26 Sep 2009 4:02 AM

Does anyone know if any FISH probes have been developed to test for the gene responsible? I would love to get that at the college's lab!

Courtney 16 Mar 2010 3:54 PM

Are there physical characteristics that go along with the large heart? I could have sworn I read that somewhere; that they have small ears and prominent withers and a long shoulder.  Can you give any credence to that?

Diane 18 Oct 2010 10:06 PM

Diane,

At the recent Pedigree & Genetics symposium four world respected equine geneticists - Dr Jamie Macleod, Dr Emmeline Hill, Dr Steve Tammariello and Dr Matthew Binns, all confirmed that the myth of the x-factor was exactly that....a myth. Three of the four geneticits mentioned above were part of the Horse Genome project that sequenced the horse's genome and Dr Binns co-wrote the original horse genome map.

While there may well be genes associated with large hearts, more specifically left ventricular size and wall mass, and indeed there will be genes that regulate heart stroke, there is no evidence whatsoever in their studies that the inheritance of such genes follows the mystical pattern as described in Marianna Haun's books.

It is romantic to think that the great mare Pocahontas has in some way weaved her magic through the maze of inheritance and recombination of genes, but it just doesn't work that way. Scientists who study heart size are now finding that the sire has just as much of a role in determining heart size of the resultant foal as the mare. As an example, in talking to quite a few of the companies that measure hearts they have mentioned independently that the stallion Tapit is almost homozygous for heart morphology with his colts and fillies getting a similar heart shape to his own. There is no fabled "x-factor" at work.

To answer your question about ear size, again another myth.

While I have to applaud her for her belief in something, what Marianna Haun wrote in her books doesn't work how she has described it and it has lead many breeders astray. Heart size and function looks to be polygenic and certainly outside the scope of something that relies totally on the x-chromosome.

Genetics is going to bring a lot of things to the table in the next few years and have a lot of misconceptions and myths like this put to bed.

brogers 19 Oct 2010 12:16 PM

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