Exercise genomic applications
Section 1 – What is exercise genomics
All bodies are not made equally, genetic variations make up only 0.1% of the variations in the human genome, but that accounts for over 3,000,000 base pairs that can be different (Lynn B. Jorde, 2003). This leaves a lot of room for total variation in genes that code for important proteins involved in exercise performance. These genes can be debilitating or add advantage to a person innate physical ability. These small changes are extremely important for optimize performance in professional athletes, improvement for gym junkies and knowledge to people that wish to know more about themselves. There are genetic epidemiology studies that show human differences “physical activity level, cardiorespiratory fitness in the untrained state, cardiovascular and metabolic response to acute exercise, and responsiveness to regular exercise.” (Claude Bouchard et al, 2014) all based on statistically relevant genetic markers.
Types of genetic variations that exercise genomics are interested are single nucleotide polymorphism (SNP) which can be genotyped. Copy number variations (CNV) which are large sequences of DNA that are repeated multiple times in the genome, this amplifies that gene to be increased in expression. Variable nucleotide tandem repeats (VNTR) are when the number of CAG sequences are presented multiple times in sequence in the DNA code. Insertion and deletion polymorphism also are a big contributor to genetic difference, which remove or insert one base from the gene region. Expression is a critical observation that can be obtained through serum levels and tissue samples. Some of the genes that were proposed as relevant may have no effect on the user because of there being more expression of the gene or less. This can affect the overall performance of the person without getting debilitated from the disposition. (Linda S. Pescatello et al 2011). It is important to present that all variations in physical activity and genetics have three factors of influence: there is genetic influences, environmental influences and the interaction between the two factors (Linda S. Pescatello, et al 2011). Saying this we know that not all of the genes we inherit can entirely effected our physically abilities.
Section 2 Exercise genomic examples
2.1: Genetic muscular variations
There has been a lot of focus on the relationship between genetics and muscle type. Muscular strength and power are types of skeletal muscle cell called red/ fast twitch muscle fibers, and repeated movements over long durations are red slow twitch muscle fibers (starkebaum, 2016). 45% of muscle fiber inheritance is due to inherited genetic factors, which influence the north American population to ether have less than 35% or above 65% of type 1 muscle fibre (Simoneau JA, et al 1995). There is around 27 gene that have been statistically proven to affect muscle fibres and muscle function (information, n.d.), these genes can be viewed on table 2.3.1 genetic muscle variations in the appendix. Out of these genes AGTR2 is a major gene shown to affect type II muscle fibre ratios to ether increase power or endurance of the predisposed.
In a high-powered study looking at how the AGTR2 is affecting skeletal muscle development, metabolism and circulatory homeostasis, it found that alleles A showed a higher percentage of slow twitch fibres for C allele than A allele carriers. AGTR2 is a gene that functions as a receptor for angiotensin II which is an integral membrane protein that mediates the development and growth of healthy cells. It has also been seen to play a role in muscle growth stimulus. (NCBI, AGTR2 angiotensin II receptor type 2, n.d.). These genetic components effect 15.2% of the variation in muscle fibre composition and can be explained by the AGTR2 genotype. The paper used a cohort of 2178 Caucasians and 1220 control subjects, the frequency of the AGTR2 C allele was found to have a 62.7% increase in endurance athletes compared to power athletes. (Mustafina LJ et al.).
The first and most widely studied gene variations for muscle fibre is the ACE (angiotensin-converting enzyme). The ACE gene plays a role in tissue growth because it is an important controller of the endocrine renin angiotensin system which is key for the circulatory system, and skeletal muscle renin angiotensin system (NCBI, 2016). There is a positive link to the D allele with the ACE genotype to show an improvement for endurance performance because of the increase in slow twitch muscle fibre ratio and production (H. E. Montgomery, et al 1999).
Section 2.2: Genetic variations effecting VO2 Max
VO2 max is the maximum amount of oxygen that can be used by an athlete. There has been a great amount of contributions to the genetics of VO2 max, especially because of being one of the only exercise phenotypes presented in a genome wide associated study (GWAS). The findings showed 39 associated genes which can be view in the appendix, Table 2.3.2 VO2 max associated genes, and 21 of those genes accounted for 49% of the variation due to genetics. The strongest associations were the ACSL1 gene which accounts for a 6% difference in VO2 training response. The PRDM1 gene, GRIN3A, KCNH8, and ZIC4 genes also showed strong associations. (Claude Bouchard, et al, 2011).
In another GWAS it concluded that NFIA-AS2 rs1572312, TSHR rs7144481 and RBFOX1 rs7191721 were 3 novel genes effecting VO2 max. These genotypes all increase aerobic performance and elite endurance athlete ability. The TSHER rs7144481 C allele increased expression of TSHR gene which increased angiogenesis and/or metabolic rate, increases aerobic performance. RBFOX1 rs7191721 G allele was associated with increased muscle function for endurance activities. The NFIA-AS2 was associated with increased VO2 max levels by 24.6-48.85 increase in VO2 max levels, and was presented in almost 96% of the elite endurance athletes and only 78% of the non-elite cohort. (II Ahmetov, et al 2014).
Section 3: applications for exercise genomics
There are around 50 personalized genomics companies that genotype and make health documents that are present around the world (International society of genetic genealogy, 2016). Out of the 50 companies only 10 of them specialize in exercise genomics. Exercise genomics can be beneficial for elite athletes to improve their fitness level, starting athletes to see innate ability, and to obtain general fitness goals faster with this knowledge. Having this information can allow the users to overcome their genetic predisposition to pass limitations and get them past the plateau to greater results.
For example, one of the most common genes for these direct to consumer information tests is the ACTN3 gene. The ACTN3 genotype C:C can identify that there is better muscle use for sprinters because the alpha actinic 3 protein is fully functional compare to the T: T genotype (SNPedia, 2016). The proteins function is to bind to z-discs and analogous dense bodies to assist in the myofibrillar actin filaments in contraction (NCBI, ACTN3 gene). Understanding this disposition can let someone perform more sprint like activities compared to endurance like activities which can accelerate progress towards fitness goals, alleviate increase risk of injury, and increase ease of physical activity. This method of genotype interpretation can be duplicated for all the statistically proven exercise genomic genes.
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