This web page was produced as an assignment for an undergraduate course at Davidson College.
Myostatin and Thoroughbred Racing Speed
"The speed gene"
The Racing Daily Form published an article discussing research about the preservation of a "speed gene" in Thoroughbred racing lineages (Oakford, 2012). Oakford cited a study done by Bower et al. that primarily focused on the history of the gene (2012). However, Hill et al. published a study confirming the association of a certain myostatin (the gene MSTN, g.66493737C/T) variation with speed in racehorses in 2011. The research from 2011 was neither cited, nor explained in Oakford's article (2012), though the article assumed the information from the lineage study (Bower et al., 2012) was based on confirmed evidence of such a gene. Using this gene as a case study, this web page aims to analyze the science behind the story and its representation in the popular media. It will be based on the guidelines set by Kua et al.'s research on the relationship between science and science reporting in today's media culture (2004). For example, Kua et al. conclude: "Because of the concerns and constraints of their profession, journalists work in a world of simple and superlative statements. The scientific world, however, moves with caution and incremental knowledge. A good translation must be consistent with its source as well as cater to its audience" (2004). Summaries of both articles will set up analysis of Oakford's article based on Kua et al.'s (2004) suggestions, while the summary of Hill et al.'s 2011 research will provide information about the "speed gene" not found in the press article and serve as a source of comparison.
Summary of Racing Daily Form's article: "Modern speed traced to British mare from 300 years ago" (Oakford, 2012)
The Racing Daily Form's 2012 article is about how the "speed gene" fits in with the past and current racing world. It is based on Bower et al.'s 2012 research on this topic, but not on the biology of the gene itself. The article explains the methods used in the lineage study, and refers to the gene variant. From reading this article, we learn of the presence of the C-allele variant and that it is somehow related to racing speed (specifically sprinting). We also learn when the gene was introduced and how it has recently spread in the Thoroughbred population due to the popularity of the stallion Northern Dancer used at stud. Moreover, the article highlights which racing trends underlined the breeding decisions that have given rise to proliferation of the C-allele.
Oakford quotes Hill (part of both research teams) to suggest how much influence horse breeders' decisions have on the genetic make-up of the racing population (2012). Oakford discusses a single factor for racing ability, the C-allele, in the context of how in-depth breeders have gone to produce quality racehorses even prior to knowledge of the gene (2012). This discussion combination could lead to a trend of breeders honing in on this and future identified genes in their stud choices.
However, without the genomic context of the gene outlined, Oakford leaves us without knowing the reach, limits, or mechanism of the gene supposed to impress us.
Summary of the research article: "MSTN genotype (g.66493737C/T) association with speed indices in Thoroughbred racehorses" (Hill et al., 2011)
Hill et al. present their study within the context of other efforts to locate physiological means to predict racing quality that has not lead to consensus as of yet (2011). Furthermore, they explain how they came across the gene as a candidate for association with racing quality. Hill et al. took the result of a genome-wide association study that showed an SNP (single nucleotide polymorphism--aka. point mutation) in the myostatin locus (MSTN) correlated with successful Thouroughbred racehorses (2011). They used the knowledge that there was some allele (deemed "C") that conferred racing ability over varying distances, even in heterozygote horses, to expand on the research and look at the allele's effect on speed (Hill et al., 2011).
First, Hill et al. outline the qualifications they followed in chosing their test horses. They chose 85 Thoroughbreds with similar training and fitness levels from one training location that were all trained for the same kind of racing (Flat racing) by a single trainer (Hill et al., 2011). In addition, they controlled for age, gender, amount of exercise and training relative to their ability in the days leading up to testing, and jockey (Hill et al., 2011). The study gathered data from an distribution of genotypes fitting with the probability of homozygosity and heterozygosity expected for a given locus. Of the test population C/C and T/T were each around 25 percent, while C/T horses made up roughly 50 percent (Hill et al., 2011).
Second, Hill et al. describe their measurement device (a GPS held by the jockey) and what they measured (2011). Their speed measurements included maximum velocity achieved, how long the horses could maintain maximum velocity, how far they traveled after reaching maximum velocity, and the acceleration of the horse as defined by the distance traveled in the six seconds leading up to the maximum velocity (Hill et al., 2011).
Third, the journal article explains their techniqe for genotyping the test horses. They discuss where they got the DNA samples from (blood), their automated purification system and PCR (polymerase chain reaction--a way to exponentially multiply the amount of DNA segments) genotyping system, and the allele-specific primers and labels used for the assay (Hill et al., 2011). This information, in combination with the first two sections, gives the reader confidence and a context in which to interpret the statistical analysis that follow.
Fourth, Hill et al. lay out the statistical techniques they used to analyze their data--a linear regression program (verified by an ANOVA test) model to link their measurements with genotypes (2011). They include the data necessary to control for the above-mentioned characteristics (Hill et al., 2011). While the section does not explain how the statistics work, it does outline the variables solved for and used. Basic definitions of various statistical tests can be found online, and you may want to start here.
Results and Key Figures:
Hill et al.’s results were statistically significant for all the speed variables assessed (2011). For the most part, the C/C genotypes outperformed the C/T in every category, while the T/T group had the lowest performance for every assesment (Hill et al., 2011). The C/C horses ran faster in the time before and after maximum velocity, had a higher maximum, and maintained maximum velocity for longer (Hill et al., 2011).
Figure 1. Verification of the significance of their data. For each speed variable tested the p-values were less than .05, showing that their results were statistically significant. Dist6, Dist6a, Dist6b correspond to acceleration measurements, Vmaxt represents the time spent at maximum velocity, and Vmax represents the peak velocity reached (Hill et al., 2011). Permission to reproduce figure granted by author 2 Febuary, 2012.
Figure 2. Comparison of genotypes. Here, we get to see how the genotypes actually related to the speed variables, represented by the mean values in each row. The heterozygotes actually outperformed the C/C horses in Dist6a and Vmaxt. These two results are important to note when Hill et al. discuss the dosage effect of the allele (2011). Permission to reproduce figure granted by author 2 Febuary, 2012.
Figure 3. Visual representation of genotype correlation to Dist6 results. This figure highlights one of the results that was part of the acceleration measurements. It more obviously shows the dosage effect of the allele than the previous figure, which is likely why they chose to focus on the results from this category more than the others. (Hill et al., 2011). Permission to reproduce figure granted by author 2 Febuary, 2012.
To start the section, Hill et al. acknowledge a limitation of their study: the sample size (2011). However, they also explain how this limitation should not cause concern. Hill et al. claim that the population they pulled from, Thoroughbreds, has experienced enough inbreeding that a small sample can accurately represent the population as a whole (2011).
In their analysis of the results, Hill et al. go beyond stating that the gene has the shown effects; they discuss the role of MSTN and myostatin in the horse at a cellular level (2011). They explain that training has an effect on MSTN transcription specifically in skeletal muscle, and even more with the C-allele (Hill et al., 2011). Myostatin negatively regulates the growth of skeletal muscle mass and the SNP studied seems to result in less myostatin (Hill et al., 2011). Thus, Hill et al. illustrate the link between the gene product and muscles important in generating speed (2011).
Other than summing up and further explaining their results, Hill et al. relate back to the racing-world context their study fits into. They suggest that the difference in speed granted by the C-allele could actually win a race for someone, and they explain their reasoning based on racing terms and statistics (Hill et al., 2011). Similarly, they suggest a possibility for future research: the mechanism behind the phenotype, and the potential of other gene interactions with MSTN (Hill et al., 2011).
Kua et al. suggest that scientific writing should engage the public by science reporters playing three main roles; translator, watchdog, and tool-giver (2004).
What Oakford (2012) could learn from Kua et al. (2004):
Translator: According to Kua et al., one role of a science reporter is to boil-down the specialized information presented in a journal article so that the public can understand the research and results without knowledge in the field (2004). Oakford focuses on the lineage study, and in the discussion of the methods behind the results only explains where Bower et al. (2012) got their samples (2012). Oakford mentions that the study "analyzed molecular and pedigree data," but does not explain what those are, how they are done, or why they are relevant to the research topic (2012). A more thorough explanation of this methodology would lead into a discussion about the gene itself, which highlights the need for a section explaining Hill et al.'s 2011 research on the gene itself. For example, Oakford talks about how the gene came into the Thoroughbred gene pool from one mare (2012), but how could one source of a mutation lead to widespread propagation of the allele? This question is left unanswered, but a discussion of the dosage effects of the C-allele found by Hill et al. (2011) could guide the audience to an understanding.
Watchdog: Kua et al. illustrate the importance of reporters acting as critics and advocates of science (2004). Oakford does play the advocate role suggesting that the results of this study could affect today's racing world based on recent breeding and racing trends (2012). However, there is no analysis on the limitations of the lineage research and Oakford forces the audience to assume the gene has a real effect on racing capabilities without discussion of Hill et al.'s 2011 research. Beyond a critique of the lineage study, a discussion of the gene's limitations would create a base layer of understanding for the public to begin to assess some of the limitations of the lineage study themselves.
Tool-Giver: In this role Kua et al. advises the scientific reporter to establish a framework for the readers to analyze the research on their own (2004). As mentioned above, contextual information about the gene itself would allow the readers to analyze the importance of the lineage research themselves. Without understanding the relevance of the gene, the audience must blindly accept the idea that it is beneficial to learn about where the gene came from. In addition, Oakford could expand on this role by asking questions. After the discussion about the context of the lineage research in the racing world, Oakford could lead the reader to question how all the recent racing trends mentioned in the article link to proliferation of this one gene.
Comparison to Hill et al. (2011):
Hill et al. (2011) explain their research with certain aspects of Kua et al.'s suggestions, but the way they follow the guidelines is geared more towards the scientific community. For example, they highlight the context their research on the gene fits into and question the merits of their own study. Early in the journal article they explain the previous studies done relating to their topic and why their research was needed and unique. This discussion requires an understanding of their methodology as well as the other research. As discussed in the summary of the article above, later on in the article they critique (but also justify) the methodology of their study. However, this explanation also requires a deep understanding of the science behind their decision.
Oakford writes about the results from the 2012 lineage study by Bower et al., but leaves out critical information and analysis based on Hill et al.'s (2011) research confirming the "speed gene's" role. The recommendations of Kua et al. (2004) highlight the shortcomings of Oakford's article, and show how science writing has a gap between what is published for people within the scientific community and what the general public has access to. Oakford does follow certain aspects of Kua et al.'s suggestions, which could lead the audience to believe the research commented on has been analyzed thoroughly enough to accept its conclusions. However, without playing all three reporter roles, Oakford does not prepare or guide the public to understand enough about the topic to realize there is likely more about the research to question and learn.
Bower, M. A., McGivney, B. A., Campana, M. G., Gu, J., Andersson, L. S., Barrett, E., Davis, C. R., Mikko, S., Stock, F., Voronkova, V., Bradley, D. g., Fahey, A. G., Lindgren, G., MacHugh, D. F., Sulimova, G., and Hill, E. W. 2012. The genetic origin and history of speed in the Thoroughbred racehorse. Nat. Comm. 3: 643.
Kua, E., Reder, M., and Grossel, M. J. 2004. Science in the News: A Study of Reporting Genomics. Public Understanding of Science. 13: 309–322.
Hill, E. W., Fonseca, R. G., McGivney, B. A., Gu, J., MacHugh, D. E., and Katz, L. M. 2011. MSTN genotype (g.66493737C/T) association with speed indices in Thoroughbred racehorses. J. Appl. Physiol. 112: 86-90.
Oakford, G. C. 24 January, 2012. Modern speed traced to British mare from 300 years ago. Racing Daily Form. http://www.drf.com/news/modern-speed-traced-british-mare-300-years-ago. 29 January, 2012.
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