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60GENETIC RESEARCH* IN SPORT - A HISTORICAL REVIEW
Pawel Ci^szczyk, Agnieszka Maciejewska, Marek Sawczuk , Krzysztof Krupecki, Pawel Radzijewski Szczecin University, Institute of Physical Culture, Poland Szczecin University, Genetics F aculty, Poland
Annotation. This study describes the history of the application of genetics in sport and the present achievements in this field. We review the main directions in genetics with regard to sport: population genetics, popular in the second half of the 20th century, based on studies of the phenotypic characteristics, without genotype pattern recognition; the beginning of research on genotype characteristics with genotype pattern recognition, and recent achievements in molecular biology, after the completion of 'The Human Genome Project' in 2003.
Key words: sports, genetics, population genetics, molecular research
Анотація. Ченшик П., Мацеєвська А., Савчук М., Крупецький К., Радзієвський П. Генетичні дослідження в спорті - історичний огляд. В статті аналізується історія застосування та сфера застосування генетичних досліджень в спорті. Наводяться відомості про застосування різних типів генетичніх досліджень в спорті, таких як: популяційна генетика - популярний метод генетичних досліджень в другій полові двадцятого століття, яких базується на вивченні фенотипічних параметрів без дослідження генетичних зразків; а також, перші відомості про застосування генетичних характеристик генетичних зразків з урахуванням сучасних досягнень молекулярної біології, після оприлюднення наукового проекту 'The Human Genome Project' в 2003 році.
Ключові слова: спорт, генетика, популяційна генетика, молекулярні дослідження.
Аннотация. Ченшик П., Мацеевска А., Савчук М., Крупецкий К., Радзиевский П. Генетические исследования в спорте - исторический обзор. В статье анализируется история применения и поле деятельности генетических исследований в спорте. Приводятся данные о применении различных типов генетических исследований в спорте, таких как: популяционная генетика - популярный метод генетических исследований во второй половине двадцатого века, основанный на изучении фенотипических параметров без исследований генетических образцов; а также данные о пионерских работах применения исследования генетических характеристик генетических образцов с учетом передовых достижений молекулярной биологии, после презентации результатов научного проекта 'The Human Genome Project'в 2003 году
Ключевые слова: спорт, генетика, популяционная генетика, молекулярные исследования
Introduction
Genetics is presently one of the most dynamically developing fields of science. With its wide range of influence and a large number of breakthrough discoveries, it has constantly affected our world since its very inception.
The changes induced by genetics in individual spheres also concern sport. For many scientists specializing in sports training, genetics is the most promising of tool that may increase the functional abilities of the human body (Bouchard et al. 1997, Booth et al. 2002, MacArtur and North 2005 et al.). Great expectations, and also great fears, associated with the development of genetics are becoming even greater with increasingly frequent examples of practical applications of molecular technology in sport and its potential use in the future.
In the years to come, genetic discoveries will continue to affect sport with an increasing intensity. The unprecedented progress in this domain makes us believe that some theoretical applications of genetics may soon become standard procedures.
The Aim of the Work
The aim of this work is to present the evolution of the application of genetics in sport and its most notable achievements.
Review of Literature on Genetics in Sport
An unquestionable father of modern genetics is Czech monk Gregor Mendel, who in 1866 published his 'Experiments of Plant Hybridization', although the very term 'genetics' was introduced by William Bateson in as late as 1906. From its very inception as a separate field of science (de facto in 1900, i.e. from the moment when the principles of heredity were confirmed), genetics has been deemed a possibility for developing other branches of science, such as medicine or agriculture. Initially, these were purely theoretical speculations, with some scientists denouncing them as improbable visions that could never be realized.
In the first half of the 20th century, genetics was a young and novice science. A low level of general knowledge on genetics (resulting in limited research funds) and poor publicity concerning its achievements were a barrier that thwarted the realization of many scientific visions. The application of genetics in sport was not even considered at that point.
The first research concerning the practical application of genetics in sport started in the 1960s and 1970s. Due to the low level of knowledge in the field of molecular biology, the studies concerned mostly the phenotypic characteristics in an unmeasured genotype approach. The studies were based on the statistical analysis of a given phenotype (or a set of genes) in the population. The phenotypic variability, thus determined, was the basis for studying the influence of genes on individual characteristics of the human body.
Initially these types of study concentrated on structural traits, due to relatively simple research procedures. The first
© Pawel Ci^szczyk, Agnieszka Maciejewska, Marek Sawczuk,
Krzysztof Krupecki, Pawel Radzijewski, 2009
of this kind was the publication on genes influencing certain body proportions and sizes, for example by Tanner and Israelsohn (1963), Furusho (1968, 1974), Kovar (1977) and Wilson (1986). In the following years, the subject matter was developed considerably, and included the distribution of fatty tissue in the body (Stunkard et al. 1986, Bouchard andsftsse 1988, Selby et al. 1989, Lucarini et al. 1990) or the proportion of muscle fibers.
Relatively later, scientists attempted to relate genetic discoveries to the functional aspects of the human body. One of the main direction here was the functioning of the circulatory and respiratory systems. One should mention here studies on the genetic conditioning of blood pressure or maximal oxygen intake (Arkinstall et al. 1974, Havlik et al. 1980, Adams et al. 1986, Fagard et al. 1987, Mongeau 1987, Redline et al. 1987, Rybicki et al. 1990 and others).
At the same time, many other interesting studies were carried out which concentrated on the genetic conditioning of motor abilities that were specific to physical effort and sport (Marisi 1977, Szopa 1982, 1986, Wolaki et al. 1980, Williams and Gross 1980, Kovar 1974, 1981 (p 348), Engstrom and Fischbein 1977, Malina and Mueller 1981, Venerando and Milani-Comparetti 1972, Sklad 1973, 1975 and others). The effect of those studies was the development of 'heritability indexes', which enabled the division of motor abilities into strongly- and weakly influenced by genes (which in an obvious fashion can be related to trainability).
This type of information has been and is still very valuable for coaches responsible, among other things, for initial selection. They indicate those factors which should be taken into consideration first. There are some notable contributions by Polish scientists, such as Szopa (1983, 1985, 1986), Szopa and Mleczko (1987) and WoMski and Kasprzak (1979).
Initially, a low state of knowledge in the area of molecular biology significantly limited the availability of research procedures. The performance of human genotype analysis (the aforementioned measured genotype approach) was impossible in those times. All the works on genetics in sport were based on methods used in the quantitative traits. One should mention here the analysis of family similarities, the twin method, or the method of adopted children.
The main advantage of these research techniques is the lack of greater technical problems with their determination (during their determination, usually no technologically advanced instrumentation was used). From a modern point of view, one needs to state that those methods had many more disadvantages than virtues.
The first problems with determination in those studies was the collection of suitable material (especially when it came to the size of the examined sets). The performance of studies on twins or adopted children narrowed the possibility of wider or truly representative scientific reports.
The greatest disadvantage of the aforementioned techniques was the interpretation of the results and the possibility of their effective use in reality. The quantitative traits could not be applied in the analysis and the interpretation of individual conditioning. The heritability determined by this method is a population measure, which in general provides only statistical proof for the participation of genetic factors in the quantitative characterization of phenotypes.
Another issue, as important and also quite controversial, was the separation of genetic and environmental factors with regard to the influence on individual phenotypes. In the initial period of genetic studies, obtaining reliable data concerning that issue was practically impossible.
Due to these and other difficulties, the verification of widely accepted views and opinions from those times was possible only some time later, along with the development of knowledge and methodology used in genetics.
Further development of studies concerning the application of genetics in sport came along with progress in molecular studies and the resultant increase in available information on polymorphic markers in the genome.
Some of the first studies on genetic markers were carried out as early as 1968 during the Olympics in Mexico. The analyses concerned the differentiation of alleles in genes associated with blood groups and vascular enzymes.
Some kind of continuation was undertaken in 1976 during the Olympics in Montreal in research aimed at finding genetic markers associated with aerobic efficiency (after Osinski 2003). Obviously, studies that used the latest achievements in molecular biology in the 1970s and 1980s were only a semblance, and the introduction, to present research. However, it is the development of those ideas and research that enabled the determination of the first known 'sport talent genes' (Gaygay et al. 1998).
The end of the 1990s witnessed a growing number of publications concerning the application of genetics in sport, including prestigious journals. Sport practitioners started considering that the presented data might answer issues that they had not been able to solve for a long time.
The work which organized the state of knowledge on sport genetics was a 1997 article 'Genetics of Fitness and Physical Performance' by Bouchard et al (1997). The author analyzed and systematized the previous research and attempted to forecast developments in the field. Many of those speculations came true in the following years.
One of the most advanced projects on the role of genes in sport was 'The HERITAGE family study” (HEalth, Risk factors, exercise Training And Genetics) commenced in 1992. All the work associated with the project was divided into 3 stages, performed during 1992-2004, and carried out at several scientific centers at the same time (Indiana University, University of Minnesota, Texas A&M University, Washington University and Pannington Biomedical Research Center).
The main aim of the project was to determine the influence of individual genes on the circulatory-respiratory system, metabolism and hormonal regulation during aerobic effort. Effort-induced metabolic changes were analyzed in detail based on parameters such as VQmax, blood pressure, HR, LA, glucose, free fatty acids)
The obtained results proved unambiguously that the character and range of the metabolic changes, which de facto
determine the trainability of players and their results, are the effect of gene expression regulation and the variability in the amount of the resultant protein and non-protein products.
Progress in studies on the human genotype in the context of sport and recreation has been gradual and multifaceted. Although some scientists tried to identify further genes and alleles that differentiated individual phenotypes, others concentrated on already mapped genes which had been recognized as determinants of individual traits. In both cases, the real breakthroughs started with the systematization and spread of information on the human genome. (The full version of the human genome took 13 years to finish in 2003, in the framework of the international 'Human Genome Project' and a project by the private corporation Celera).
The dynamics of developments in genetics since that time is well described by the sheer number of publications on the issue. For example, before 2000, leading journals published about thirty works on genetic markers in endurance sports, power sports and speed sports and the genetic markers in the performed efforts (in proportion 20:2:8), while after 2005, the proportion in publications in the same journals was 53:23:32. What is more important is that the number of such publications is still growing (Roth 2007)
One of the first genes that was strictly related to sport achievements was ACE gene, responsible for encoding the angiotensin enzyme (for example regulating the flow of blood in working muscles). An article by Gaygay et al. (1998) is an early work that proved the significance of ACE gene in endurance sports - insertion form of the ACE gene is much more frequent among rowers than in the general population. Others from early studies on genetic markers concerned myostatin, responsible for muscle tissue mass. (McPherron et al. 1997, Ferrell et al. 1999).
Another gene, which was relatively early related to sport achievements was ACTN3, responsible, among other
things, for the proportion of muscle fibers. A detailed review of studies on this gene and its significance for power/speed
sports was presented by Bouchard et al (1997) and most recently by Roth (2007).
The aforementioned genetic studies are obviously only a few examples. The number of genes that have been mapped and related to sport achievements is of course much higher and, what is more important, it is dynamically growing. In 2001 researchers related only 29 genes to sport achievements. In 2006, a significant correlation to sport results was observed for 170 genes (Rankinen et al. 2006). Importantly, the diversity of the examined sport-related genetic influences increases. Presently carried out analyses not only concern genes responsible for metabolic pathways or body structure, but even those related to emotions and character types, such as AVPR1a and SLC6A4 (Bachner-Melman et al. 2005).
The most frequently described genetic markers are those which determine the body structure (e.g. GDF8, ADRB2, ADRB3, NPY, VDR, LPL, IGF l and ACE), hemodynamic phenotype (e.g. AGT, ADRB2, EDN l, ANG, TGFB1), and muscle strength (e.g. GDF8, VDR, COL1A1, ACE), glucose and insulin metabolism (e.g. ADRB3) or blood lipid and fat metabolism (e.g. Apolyprotein sample) - after Sanocka and Kurpisz (2004).
The very evolution of views on the potential use of genetics in sport has been interesting in itself. The initial works concerned first of all the application of genetics in the selection process. Osinski (2003, p. 89) in one his works states: 'there are certain possibilities, thanks to the use of special genetic probes, to identify exceptionally talented and highly trainable individuals'.
Such claims will be even more justified if we identify - among others - the gene that is the most significant for a given element of performance. Bouchard et al (1997) were even predicting that genes 'unambiguously determining certain sport predispositions', in the case of endurance predispositions, would be discovered between 2010 and 2015. Today we know already that establishing a genetic factor that authoritatively decides on sport predispositions is practically impossible (for example due to the polygenecity of traits)
Other examples of using genetics in sport is in gene doping, or even the alteration of the human genotype in order to create a 'super-sportsman'. The ethical side of this issue was discussed in 'Genetics technology and sport - ethical questions' by T amburrini and Tinnsjo (2005). Although some of the problems described by the authors belong rather to the domain of 'science-fiction', the sheer dynamics of changes in genetics does not allow the exclusion of any, even the least probable possibility.
The possibility of practical applications of genetics in sport have increased together with developments in methods and research techniques used in this field of science. Initially, genetics was used to estimate the probability of achieving parameters that were significant for the level of sport expertise (the most common estimation was based on family relations: if a father and mother are tall, then their child will also be tall). Many coaches responsible for training children and youth still use such methods in their work. The final verification of such presumptions (very often erroneous) was possible thanks to the development of molecular techniques.
Presently, the majority of works on the application of genetics in sport, apart from ethical issues, concern the multifaceted analyses and comparisons of alleles from individual genes that determine the traits of the human body and are perceived crucial from a sport perspective. So far, the resulting information is used mostly in the selection process. In the future, however, its significance for sport practice and theory may increase considerably.
The very range of influence and practical application of genetics in sport in the future is very difficult to predict. This is so, as it difficult to forecast the moment of new genetic discoveries and the resultant advances. One such breakthrough discovery was the PCR technique of DNA reproduction by Mullis, for which he was awarded a Nobel Prize. It enabled things that had been previously thought belong to the domain of science-fiction, as it shortened the time of biochemical
reactions from a few years to a few dozen minutes. What then will happen in the future?
Even today, the use of genetics in sport could be much wider, starting from indices that could help draw a correct training plan, to gene doping. The key issue here (apart from technical problems which might be considered temporary) is the ethical side of such actions (Chrostowski 2005).
The aforementioned facts show one more thing. Genetics is one of those few branches of science in which research is accompanied by the serious analysis of its ethical consequences. In the history of science, there have been many cases of achievements, the implementation of which were controversial from the very beginning (such as the invention of dynamite by Alfred Nobel).
However, in sport the situation is opposite. Ethical issues associated with the application of genetics for sport purposes are widely discussed and analyzed, anticipating the present possibilities of science. One could mention here works by Lippi et al. (2004), Miah (2002), Schneider and Friedmann (2006), and the aforementioned 'Genetics technology and sport - ethical questions' (Tamburrini and Tinnsjo 2005).
Conclusion
The sense of using genetics in sport does not seem to be questioned. This has been proven by diverse research at various scientific centers in North America, Asia, Australia and Europe. The financial support for research is increasing quickly, together with the growing number of research teams. Although 'knowledge on genetic predispositions in physical performance is still at the level of early kindergarten' (Sanocka and Kurpisz 2004), the very progress in genetics that we witness shows that it will surely be one of the crucial factors in the future of sport.
References
1. Adams T., Yanowitz F., Fisher G., Ridges J., Nelson A., Hagan., Williams R., Hunt S., Genetics and cardiac size. In: Malina R., Bouchard C. eds. Sport and human genetics. Champaign. Human Kinetics.131-45. 1986
2. Arkinstall W., Nirmal K., Klissouras V., Milic-Emili J., Genetic differences in the ventilatory response to inhaled CO2. J.Appl.Physiol. 36:6-11, 1974.
3. Bachner-Melman R., Dina C, Zohar A, Constantini N., Lerer E., Hoch S., Sella S., Nemanov L., Gritsenko I., Lichtenberg P., Granot R., Ebstein R., AVPR1a and SLC6A4 gene polymorphisms are associated with creative dance performance. PLoS Genet 1(3): e42. 2005
4. Booth FW., Charkravarthy MV., Spangenburg EE., Exercise and gene expression: physiological regulation of human genome through physical activity. J Physiol, 2002; 543:399-411
5. Bouchard C., Simoneau J.A., Lortie G., Boulay M.R., Marcotte M., Thibault M. C., Genetic effects in human skeletal muscle fiber type distribution and enzyme activities. Can. J. Physiol. Pharmacol. 64. 1245-1251, 1986
6. Bouchard C., Malina R., Peruse L., Genetics of fitness and physical performance. Champaign Human Kinetics. 1997.
7. Bouchard C., Perusse L., Heredity and body fat. Ann. Rev. Nutr. 8, 259-277, 1988.
8. Chrostowski K., Doping genowy - nowe zagraenie dla sportu. Sport Wyczynowy, 9-10:91-99. 2005.
9. Engstrom L., Fischbein S., Physical capacity in twins. Acta Genet. Med. Gemellol. 26:159-65. 1977.
10. Fagard R., van Den Broeke C., Bielen E., Amery A., Maximum oxygen uptake and cardiac size and function in twons. Am. J. Cardiol. 60:1362-67. 1987.
11. Ferrell R., Conte V., Lawrence E., Roth S., Hagberg J., Hurley B., Frequent sequence variation in the human myostatin (GDF8) gene as a marker for analysis of muscle-related phenotypes. Genomics. 62:203-207. 1999.
12. Furusho T., On the manifestation of genotypes responsible for stature. Hum . Biol. 40:437-455, 1968.
13. Furusho T., Genetic study on stature. Jpn. J. Hum. Genet. 19:1-25, 1974
14. GaygayG., Yu B., Hambly B., Elite endurance athletes and the ACE I allele - the role of genes in athletic performance. Human Genet., 103, 48-50. 1998.
15. Havlik R., Garrison R., Fabsitz R., Feinleib M., Variability of heart rate, P-R, QRS and Q-T durations in twins. J. Electrocardiol. 13:45-48, 1980.
16. Kovar R., Prispevek ke studiu geneticke podminenosti lidske motiriky. Doctoral dissertation. Charles University. Prague. 1974.
17. Kovar R., Somatotypes of twins. Acta Univ. Carol. Gymn. 13; 49-59; 1977.
18. Kovar R., Human variation in motor abilities and its genetic analysis. Charles University. Prague. 1981
19. Lucarini N., Finocchi G., Gloria-Bottini F., Macioce M., Borgiani P., Amante A., Bottini E., : A possible genetic component of obesity in childhood: Observations on acid phosphatase polymorphism. Experientia. 46, 90-91,1990.
20. Lippi G., Solero G., Guidi G., Athletes genotyping: ethical and legal issues. Int J Sports Med 25(2):159. 2004
21. MacArthur D., North K., Genes and human elite athletic performance. Hum. Genet. 116:331-339, 2005.
22. Malina R., Mueller W., Genetic and environmental influences on the strength and motor performance of Philadelphia school children. Hum.Biol. 53:163-79.1981.
23. Marcotte M., Chagnon M., CBte C., Thibault M., Boulay M.R., Bouchard C., Lack of genetic polymorphism in human skeletal muscles enzymes of the tricarbioxylic acide cycle. Hum. Genet. 77:200, 1987.
24. Marisi D., Genetic and extragtenetic variance in motor performance. Acta Genet. Med. Gemellol. 26:197-204. 1977.
25. McPherron A, Lee S. Double muscling in cattle due to mutations in the myostatin gene. Proc. Nat. Acad. Sci. USA. 94:12457-12461. 1997.
26. Miah A., Bioethics, sport and the genetically enhanced athlete. Med Etika Bioet. 9(3-4):2-6. 2002.
27. Mongeau J., Heredity and blood pressure in humans. An overview. Pediatr. Nephrol. 1:69-75, 1987.
28. Osinski W., Antropomotoryka, AWF, Pozna 2003.
29. Rankinen T., Bray M., Hagberg J., Perusse L., Roth S., Wolfarth B., Bouchard C., The Human Gene Map for Performance and Health-Related Fitness Phenotypes: The 2005 Update. Special raport, Medicine & Science in Sports & Exercise. 38 (11): 1863-1888, 2006.
30. Redline S., Tishler P., Lewitter F., Tager I., Munoz A., Speizer F., Assessment of genetic and nongenetic influences on pulmonary function. Am. Rev. Resp. Dis. 135:217-22, 1987.
31. Roth S., Genetics primer for exercise science and health. Champaign Human Kinetics. 1997.
32. Rybicki B., Beaty T., Cohen B., Major genetic mechanisms in pulmonary function. J. Clin. Epidemiol. 43:667-75,1990.
33. Sanocka D., Kurpisz M., Genetyczne aspekty wysiku fizycznego [w:] Medycyna Sportowa pod red. Mdrasia M. Agencja Wydawnicza Medsportpress. Warszawa. 2004.
34. Schneider A., Friedmann T., Gene doping in sports: the science and ethics of genetically modified athletes. Adv. Genet. 51:1-110. 2006.
35. Sklad M, Rozwoj fizyczny I motorycznsc blizni^t. Materialy I Prace Antropologiczne. 85:3-102. 1973.
36. Sklad M, The genetic determination of the rate of learning of motor skills. Stud. Phys. Anthropol. 1:3-19. 1975.
37. Sleby J.V., Newman B., Quesenberry C.P.Jr., Fabsitz R.R., King M. C., Meaney J.M., Evidence of genetic influence on central body fat in middleaged twins. Hum. Biol. 61, 179-193. 1989
38. Stunkard A.J., Foch T.T., Hrubec Z., A twin study of human obesity. JAMA. 256, 51-54, 1986.
39. Szopa J., Familial studies on genetic determination of some manifestations of muscular strength in man. Genet.Pol. 23:65-79, 1982.
40. Szopa J., Genetic control of fundamental psychomotor properties in man. Genet. Pol. 27:137-50, 1983.
41. Szopa J., Zmiennosc oraz genetyczne uwarunkowania niekOrych przejawow sily mi^sniowej czlowieka. Wyniki badan rodzinnych. Mat. i Prace Androp. nr 103. 1983.
42. Szopa J., Zmiennosc ontogenetyczna, zroznicowanie srodowiskowe oraz genetyczne uwarunkowania rozwoju komponentow ciala w populacji wielkomiejskiej w przedziale wieku 7-62 lat. Wyd. Monogr. AWF, Kralw, nr 22. 1985.
43. Szopa J., Genetyka w wychowaniu fizycznym I sporcie - wybrane zagadnienia metodologiczne.. Wych. Fiz. i Sport, nr
2. 1986.
44. Szopa J., Mleczko E., Genetyczne uwarunkowania czasu reakcji. Wych. Fiz. i Sport, nr 3. 1987
45. Tanner L., Israelsohn W., : Parent-child correlations for body measurments of children between the age of one month
and seventy ears. Ann. Hum. Genetics. 26; 245-59; 1963
46. Tamburrini C.,Tannsjo T., Genetics technology and sport - ethical questions. Routledge. Abingdon, 2005.
47. Williams L., Gross J.., Heritability of motor skill. Acta Genet. Med. Gemellol. 29:127-136, 1980.
48. Wilson R., Twins: Genetic influence on groth. In: Malina R., Bouchard C. eds. Sport and human genetics. Champaign.
Human Kinetics. 1-21, 1986.
49. Wolaiski N., Kasprzak E., Similarity in some physiological, biochemical and psychomotor traits between parents and 2-56 years old offspring. Studies in Human Ecology, vol. 3. 1979.
50. Wolaiski N., Tomonari K., Siniarska A., Genetics and motor development of man. Hum. Ecol. Race Hyg. 46:169-91. 1980.
51. Venetando A., Milani-Comparetti M., Twins studies in sport and physical performance. Acta Genet. Med. Gemellol. 19:80-82. 1972.
Came to edition 06.03.2009.
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