Genetics in Sport (AP) PDF

Genetics and Sport Anna Derrick [email protected]  Quiz Test your knowledge from last lecture! (Chernobyl) https://kahoot.it Also available on: Learning Ou...

Genetics and Sport Anna Derrick [email protected]  Quiz Test your knowledge from last lecture! (Chernobyl) https://kahoot.it Also available on: Learning Outcomes Outline the role of genetics in sport performance. Provide examples of genes implicated in sport performance. Understand the physiological characteristics of the Kalenjin Tribe that enhance their distance running ability. “We used to think that our fate was in our stars, but now we know that, in large measure, our fate is in our genes” James Watson (co-discoverer of DNA structure). Genetic factors in Sport Performance On average, 66% (depends on sporting discipline) of the variance in athlete status can be explained by additive genetic factors. The remaining variance is due to nonshared environmental factors. Starting in the late 1990s, research began to identify DNA polymorphisms associated with certain types of sports and exercise-related phenotypes. Despite a relatively high heritability of athlete status, the search for genetic variants contributing to success in certain types of sport has been a challenging task. Sport performance Complex polygenic multifactorial trait. Polygenetic: Determined by multiple genes so do not follow Mendelian inheritance. Many polygenic traits are also influenced by the environment: Multifactorial. Traits with a range of phenotypes. Majority of physical, behavioural and metabolic traits. Examples – Height, weight, intelligence, heart disease, type 2 diabetes. Phenotypes influencing sport performance Flexibility Balance Cardio vascular Coordination fitness Muscle strength Weight Muscular endurance Height Muscle fibres Intellect Factors influencing sport performance Training and Injury motivation Genetic Potential Sport Performance Access to Equipment Physical environment Nutrition Genetic Association Studies - Sport Performance When a genetic variant occurs more often than by chance in a population of individuals with a particular phenotypic trait. Study design: Case–control studies: elite athletes vs general population. Endurance athletes vs power athletes - located at opposite extremes of the muscle performance. Quantitative traits measurable – VO2max, strength measures, percentage of fast-twitch muscle fibres, cardiac size, lactate. Genotype- Phenotype Association Studies Candidate Gene (hypothesis driven) Biological Candidate gene/region Hypothesis Genotyping Candidate Gene Genotyping Methods Restriction Fragment Length Sanger Sequencing Polymorphism (RFLP) Genotype- Phenotype Association Studies Candidate Gene Genome Wide Association Study (GWAS) (hypothesis driven) (hypothesis free) Biological Candidate gene/region Hypothesis Genotyping Genotyping GWAS Genotyping Methods Microarray Next Generation sequencing (NGS): Whole Exome Sequencing (WES) or Whole Genome Sequencing (WGS) Single Nucleotide Polymorphisms (SNPs): Allele/Variant observed in at least 1% of the population. Genotype- Phenotype Association Studies Candidate Gene Genome Wide Association Study (GWAS) (hypothesis driven) (hypothesis free) Biological Candidate gene/region Hypothesis Genotyping Genotyping Biological Detection and fine mapping of Hypothesis association signals (p 7000 m compared to controls. Montgomery, et al. (1998) Human gene for physical performance. Nature, 393:221–22 ACE genotype frequency in 91 Olympic runners. Control group genotype frequency was II = 0.24, ID = 0.5, and DD = 0.26 Jones, et al., (2002) Human Performance: A Role for the ACE Genotype? Exerc Sport Sci Rev, 30(4):184-90 ACE I/D polymorphism ACE I/D polymorphism, alters activity of the encoded enzyme. I allele associated with lower ACE activity corresponding to increase in muscle efficiency seen in endurance athletes. D allele associated with higher ACE activity and angiotensin II which is a growth factor therefore linked with power-related strength like weight lifting. Vancini, et al., (2014) Genetic aspects of athletic performance: the African runners phenomenon. Journal of Sports Medicine, 5:123–127. Ostrander, et al., (2009) Genetics of Athletic Performance. Annu Rev Genomics Hum Genet, 10:407–29.  ACTN3 ACTN3 is located on chromosome 11q13.2. ACTN3 encodes an alpha actin 3 binding protein. Primarily expressed in skeletal muscle and functions as a structural component. Two types of muscle fibre: Type I (slow twitch) and Type II (fast twitch). ACTN3 predominantly found in type II which are responsible for generating forces at high velocity during explosive or powerful activities.  ACTN3 p.Arg577Ter Polymorphism ACTN3 has 20 exons p.R577X Polymorphism NM_001104 c.1729C>T, Exon 16 NP_001095, p.Arg577Ter (rs1815739) XX homozygotes are deficient in ACTN3. RR homozygotes have greater numbers of type II fibres.  ACTN3 p.Arg577Ter polymorphism studies ACTN3 genotype frequency in controls, elite sprint/power athletes, and endurance athletes. Reduction in the frequency of the ACTN3 577XX genotype in elite sprint athletes. Yang, et al., (2003) ACTN3 Genotype Is Associated with Human Elite Athletic Performance. Am. J. Hum. Genet. 73:627–631. ACTN3 genotype in male Caucasian 200 meter sprinters individual against running times. Qualifying time (QT) for the Olympic Games (20.65 s). Papadimitriou, et al., (2016) ACTN3 R577X and ACE I/D gene variants influence performance in elite sprinters: a multi-cohort study. BMC Genomics, 17:285. Genome Wide Association Studies  The Nandi of the Kalenjin Tribe, Kenya The Kalenjin tribe are from the highlands of the Rift Valley of Kenya. The Kalenjin Tribe make up 0.07% of the Worlds population yet have won 34% of all global medals in middle distance and long-distance running events since 1964. Culture, diet, altitude training and environment has been described to be contributing factors to their success. But what about their physiological Kipchoge Keino Asbel Kiprop characteristics and associated genetics? 1968 Olympics 2008 Olympics 1500m Gold medal 1500m Gold medal Tucker, et al., (2015) Analysis of the Kenyan Distance-Running Phenomenon. International Journal of Sports Physiology and Performance, 10:285-291. The Kalenjin Tribe - Physiological characteristics Volume and average thickness of the lower legs is 15-17% less than control populations - increase running economy and reduce energy expenditure. Exceptionally long Achilles tendons compared to control population – generate more power because more elastic potential. Less mass for their height, longer legs, shorter torsos, and more slender limbs – ‘Nilotic’ build. Nature vs Nurture Both South Sudanese and Kalenjin people have Nilotic build. So why is there a disparity in the presence of the running world stage? Nature Nurture Genes and hereditary factors. Environmental variables. Characteristics inherited from Characteristics developed from parents. experience and environment. The Lost Boys of South Sudan South Sudan Nurture Travel difficulties Historical discrimination Civil War NO sports culture or infrastructure 20,000 orphaned boys who fled the second Sudanese civil war (1987-2005). Many of the refugee boys were taken to America. Within months of arrival several made a name for themselves on the high school and college stage. Lopez Lomong 2012 Olympics 5000m 10th In Kenya the statistical projection is that 80 men out of every million have world class running talent, compared to one in every 20 million men in the rest of the world. That brings an end to todays lecture – thank you for listening. If you have found this topic interesting a great book to have a read of is the Sports Gene by David Epstein.