Wednesday, September 7, 2011

2011 Pedigree and Genetics Symposium, Lexington, Kentucky.

Professor Jamie McCleod of UK began the symposium by going over basic genetics.

2:44


Bill Oppenheim is here! Lol.

Speaking on The Myths we live by: Data we use and its limitations strategies for a chaotic universe.

Racing is a business without borders, a free market economy, and there is is a finish line. The best horse wins.

Both scientists and pedigree students want to replicate the successful patterns of good horses. That which has happened before is more likely to happen again. The question is exactly what is it thatl we're looking for.

Pitfalls:
Small sample size: early success leads to breeders following the hot cross, which later falls prey to the law of averages. Storm Bird/Secretariat mares. First 8 crops 36% SW, last 10 crops 2% SW. Overall actually just an average cross for the sire.

As soon as we know something works, it's outdated, because there's a 4 or 5 year lag between mating and result. Lines wax and wane in strength. It is a myth that once we discover a great cross all we have to do is continue to do it. The greater the numbers the less the success.

Bill doesn't much care for the nicking companies, he makes it pretty clear. As usual, the problem is with numbers and quality. There are too often not enough cases to reliably predict anything. Bill is much more interested in accurately identifying success.






1:40 p.m.


Skipped over Bill Oppenheim to go next with Sid Fernando on adding stamina to the Thoroughbred.

Stamina in this country is analogous to low "good cholesterol"....Got to pay attention or we'll have a heart attack.

Early 1970s--2 G1 equivalents at 1 3/4 miles or more. No G1 races at 6 furlongs. We gave more weight to distance and less to speed. Today 20 G1 6-7 furlong races for 3yos and up. None over 1 1/2 miles. Europe and Japan have continued on a path in racing and bloodlines where stamina has remained importance.






1:00 p.m.


Steve Tamariello of Performance Genetics is next.

Discarded the test he promoted last year and now focusing on performance tests through linkage disequilibirum....which is non-random association of alleles at two or morel loci, not necessarily on the same chromosome. Wants to identify genetic variants associated with speed, using linkage disequilibrium (?).

American horses have a distinct phenotype for dirt track races. Chose peak Beyer speed as their measure of racing ability. Separated population into 2 stringent categories.
Grade 1 winning 108 or higher, but no G3 or Listed SW, or allowance horses. non-Elites =78 or lower Beyer speed, generally similar quality sires and dams.

Sample size=60.....Again sample size. But then later says 365 horses without reconciling the two numbers. Who knows.

Found associations to elite performance on ten different chromosomes....more than other researchers have found.

Most interesting thing Tamariello shows is that according to their performance test, Mineshaft and Pretty Discreet both test as route runners, Mineshaft elite, Pretty Discreet not so much, but their son Discreetly Mine tests as a G1 sprinter, which is exactly what he was.






11:12 a.m.


That was fun. Emmeline basically stonewalled Lambert's question (see below for her answer). The controversy between Lambert/Binns and Hill comes basically from the fact that Hill makes bigger claims for the power of her tests than other geneticists do, and they do not take that lightly. And since in the modern world whoever yells loudest gets the most attention, it turns out to be quite important commercially.

Stephen Harrison up next.

Contrary to popular belief, the Thoroughbred is quite outbred compared to many other breeds. It's a probability model, and the more tests you have the better predictor you have.

Harrison's specialty has been Mitochondria, so he dives right in on that.

Original 2006 study found 13 different functional MtDNA genes. Looked at variations in stamina levels, quality, interaction with stallion mtDNA, etc. 33 different mtDNA types in Thoroughbred.

Some evidence of positive interactions between stallions and particular mtDNA types in mares. Invincible Spirit and Fusaichi Pegasus, for example did better than expected with certain types. No mention of sample size however. Small study showed that best ratios of mtDNA to nuclear DNA was for mtDNA type to same mtDNA type between sire and dam.

Someone from Emmeline's school attacks Harrison's data about mtDNA from males mixing. Says it's very well established that mtDNA is very well established coming only from the female in mammals. Harrison tries to defend. This is basically over everybody else's head except for the scientists. Harrison doesn't really answer.





10:00 a.m.


Brief set of questions from audience. Emmeline Hill up next. This could get interesting.

Emmeline begins by saying only four genes have been definitely identified as associated with performance in Thoroughbreds. Naturally, all of those are from her studies as far as I can tell from the slide.

Begins with rehashing Myostatin and her so-called "speed gene". Not a test for class, but only for preferred distance. Still insists that her marker for Myostatin is more accurate than other markers, in contradiction to what Matthew Binns showed in his talk.

Largest change in the expression of the myostatin gene due to training is in the CC sprint type. In other words, CC horses respond more quickly and more precociously to training than CT or TT horses. That is an interesting finding, confirmation that CC is related to precocity. It makes sense that the sprint genotype would have a big influence on 2yo racing.

Moves on to PDK4 gene's association with performance. First found an association but could not replicate. Then looked for novel variants that might have some effect, but again couldn't replicate original findings. Hypothesized that different genes may be interacting with the myostatin gene. Found a strong association with the stamina type horses, so implies that PDK4 gene is important for longer distance exercise, but not shorter distances.

Elite performance test. You get stronger results from the CCs and TTs, but different genes associated with performance in the different types. This is related to why what used to be called fish and fowl matings generally don't work....Different genes are required for success at shorter and longer distances, and therefore and they don't work together that well.

Technology is not a silver bullet, but it will increase your chances of improving your strike rate.

Hill's Class 1 and Class II horses earned more money than they cost at sales. Class III and IV did not.

That's a good result, but the problem for Hill is that she only uses blood samples not hairs. Therefore her tests are useless as a way of cutting down your short list at a sale, because it takes two weeks to get a result. Cannot be done overnight like hair sample tests. That's the source of the contention between Hill and Binns over which test is more accurate.

Uh Oh. David Lambert of Genetic Edge challenge's Hill on the numbers in her sample size.

Hill responds that they are capturing genetic potential, management and environment are hugely important. Equinome has applied for an international patent on myostatin that includes other people's markers....that's going to be trouble. In response to numbers, she claims even in small sample size, the proof is strong. "of course the more samples you have the more power that you have, but what we're able to do is capture the genes having the greatest influence on performance."









9:00 a.m . 
Matt Binns up next.

Matt will cover:
Genetic perspective on traditional pedigree methods; Characteristics of genetically complex traits;
Genetic Edge products---

Pedigree is a surrogate for genetics. The thoroughbred is a perfect playground for geneticists because of the 300 years of records.

Good illustration using Zenyatta's pedigree of how her 5x5 inbreeding to Nashua actually works genetically. The statistical chances of getting the same genes from both of her crosses of Nashua are actually very small.

Binns thinks nicking exists....Complementary positive genes being inherited, but it operates at a relatively low probability because of the basic facts of genetic inheritance.

There has been a slight increase in %inbreeding since the 1960s, according to comparative DNA genomes, but it's only slight. Reinforces Bailey's point about diversity.

Correlation between 8-generation coefficient of inbreeding from pedigree and what you get if you do it by DNA testing is very low. Surprising result. The problem is that there are a limited number of variants at sites in horses but they can come from different sources than what genetic theory says.

Presents new research that produced loci for white coat color markings in Thoroughbreds.

Now we're smoothly into the Genetic Edge pitch. The familiar ABCD scoring system. Data predicts that the performance panel can eliminate about 50% of individuals from short list and retain about 75% of the short list. Only 5% of Grade Ds are Graded SW.

10% of pop are As, Bs and Cs are 40% each. A's increase your chances of getting GSW 3 to 1.

Distance marker: If you want to win a G1 sprint, you'd better be homozygous for the distance marker (myostatin). About half the Kentucky Derby winners, though are also homozygous for the sprint distance marker.

Goes after Emmeline's claim that her test is more accurate, and effectively debunks it. The gloves are off this year folks.

Concludes that this is still fairly young science. This speaks to one of the big problems with acceptance and use of genetic tests. Everybody wants to wait five years until they can see the results of predictive studies.







8:50 a.m.

Now Dr. Ernie Bailey is applying what Jamie said to horses.

Gus emphasizes that contrary to popular belief, there is still a lot of genetic diversity to exploit in Thoroughbreds. Thoroughbreds are genetically less diverse than other horses because of 300 years of selection for speed, soundness and stamina, but they are far more diverse than other species that might look more diverse like dogs.



I'll be live-blogging periodically from the second annual Pedigree and Genetics symposium at the Griffin Gate Hotel in Lexington today.

The first two speakers are covering basic genetics, so there's not that much of interest there, but then the fun should start with Matthew Binns of the Genetic Edge, so check back later.


8 comments:

  1. This is interesting, John. Sounds a bit tedious to actually sit through, however.

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  2. Thanks for your work, John. I share what I gather to be your basic skepticism, particularly at this early stage.

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  3. It went on a bit long this afternoon, but then again, I didn't sleep well in a strange bed, so I was tired. Bob said you might be there tomorrow for show and tell?

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  4. Thanks Tinky,

    My question at the end of the day for the scientists was where do they expect we'll be in 5 years. The science works. It's going to be a very useful tool, in fact is already for eliminating a significant number of horses, but the sample size is too small at the moment for the confidence you really need. In five years time, they'll have the sample size and a track record of predicting x% of GSW, and x% of bums, etc. That's when they'll deserve to reap the benefits.

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  5. I agree that as time passes, the approach will be refined. What I remain uncertain about, is whether or not the use of such technologies will prove a significant advantage over good, old-fashioned horsemanship, by which I mean a smart reading of pedigrees, coupled with a practical understanding of physical characteristics.

    When Ray Paulick did a piece (in June) on Dr. Hill's work, he reported her asserting that:

    "CT horses were found to have a mixture of speed and stamina, so their optimum range was 7 – 12 furlongs."

    To which I responded:

    Optimum range of 7-12 furlongs? Seriously? This is trumpeted as a major step forward, and yet they are unable to distinguish milers from middle-distance runners (in European terms)? Any competent horseman or student of the game can predict likely distance abilities and limitations with greater precision. Given pedigree and physical type, I'd trust the eyes and knowledge of any serious professional over this DNA test.

    If they care to catch the interest of the skeptics (myself included), they should reveal pedigrees and photographs of the "CC" winners, and highlight those which, in classical terms, suggested that they should have been capable of staying a mile or beyond. In other words, If there were more than a few rare, anomalous examples of CC horses that had physical types and pedigrees that were typical of later-developing horses suited to a mile and beyond, then it would become interesting.

    Until I see some evidence of that, though, and I won't be holding my breath, I will skeptically assume that such tests reveal little more than students of pedigree and physical type would be able to discern without them.

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  6. Genetics is going to be simply another tool to help eliminate horses from a short list, and as such has some value right now, just not as much as it will have in 5 years.

    In my view the Irish Tigress tends to over sell her findings, and she has by far the best marketing machine behind her, but ultimately I'm afraid that overselling will hurt her cause. I hope not, because I think she's trying to do it right.

    It's only a matter of time before it's considerably more valuable, but it's never going to replace good old fashioned horsemanship--and none of the geneticists would say it should--but simply be another valued adjunct tool.

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  7. Thanks for the updates from the symposium.

    Did Harrison present evidence for paternal transmission of mtDNA?

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  8. John E. Madden, one of the greatest breeders of all time, wrote as follows: "As to the so-called intricate science of breeding in so blending the blood of the sire and the dam that winners may be produced in numbers, although of absorbing interest to the student and theorist, the practical man need confine himself to the formula only of breeding a good mare to a great horse taking into due consideration the varying qualities of each, and putting his trust in like producing like, or the likeness of some good ancestor. He will have his share of winners, inn his good years and bad years, and the experts will tack figures on to the pedigrees of his winners, and tell him how it all happened."

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