Genomics as a practical tool in sport - have we reached the starting line?

The genetic component of athletic performance approximates 50%, depending on which specific element of performance is considered. Limited genetic testing is already available commercially and genetic tests are likely to become powerful tools to improve sport performance in the future. Currently, however, selection of athletes for training squads or competition based on genomic data is premature. Larger volumes of longitudinal data within individual sports are needed to determine the efficacy of using genomic data in the management of elite athletes via manipulation of training load and diet based on personal genomic information

Genetic testing in exercise and sport - have direct-to-consumer genetic tests come of age?

The general consensus amongst sport and exercise genetics researchers is that genetic tests based on current knowledge have little or no role to play in talent identifi cation or the individualised prescription of training to maximise performance or minimise injury risk. Despite this, genetic tests related to sport and exercise are widely available on a commercial basis. This study assessed commercially-available genetic tests related to sport and exercise currently marketed via the internet. Twenty-two companies were identified as providing direct-to-consumer (DTC) genetic tests marketed in relation to human sport or exercise performance or injury. The most commonly-tested variant was the R577X SNP in the ACTN3 gene, tested by 85% of the 13 companies that appear to present information about their genetic tests on websites - which corresponds with our assessment that ACTN3 R577X is currently the polymorphism with the strongest scientific evidence in support of an association with sport and exercise phenotypes. 54% of companies that present information about their genetic tests used panels of 2-21 variants, including several with very limited supporting scientific evidence. 46% of companies tested just a single variant, with very low ability to explain complex sport and exercise phenotypes. It is particularly disappointing that 41% of companies off ering DTC genetic tests related to exercise and sport did not appear to state publicly the genetic variants they assess, making scrutiny by academic scholars and consumers impossible. Companies off ering DTC genetic tests related to sport and exercise should ensure that they are responsible in their activities

Age-Related Differences in Susceptibility to Carcinogenesis. II. Approaches for Application and Uncertainty Analyses for Individual Genetically Acting Carcinogens

In an earlier report we developed a quantitative likelihood-based analysis of the differences in sensitivity of rodents to mutagenic carcinogens across three life stages (fetal, birth to weaning, and weaning to 60 days) relative to exposures in adult life. Here we draw implications for assessing human risks for full lifetime exposures, taking into account three types of uncertainties in making projections from the rodent data: uncertainty in the central estimates of the life-stage–specific sensitivity factors estimated earlier, uncertainty from chemical-to-chemical differences in life-stage–specific sensitivities for carcinogenesis, and uncertainty in the mapping of rodent life stages to human ages/exposure periods. Among the uncertainties analyzed, the mapping of rodent life stages to human ages/exposure periods is most important quantitatively (a range of several-fold in estimates of the duration of the human equivalent of the highest sensitivity “birth to weaning” period in rodents). The combined effects of these uncertainties are estimated with Monte Carlo analyses. Overall, the estimated population arithmetic mean risk from lifetime exposures at a constant milligrams per kilogram body weight level to a generic mutagenic carcinogen is about 2.8-fold larger than expected from adult-only exposure with 5–95% confidence limits of 1.5-to 6-fold. The mean estimates for the 0- to 2-year and 2- to 15-year periods are about 35–55% larger than the 10- and 3-fold sensitivity factor adjustments recently proposed by the U.S. Environmental Protection Agency. The present results are based on data for only nine chemicals, including five mutagens. Risk inferences will be altered as data become available for other chemicals

Fragmentation by major dams and implications for the future viability of platypus populations

The evolutionarily unique platypus (Ornithorhynchus anatinus) has experienced major declines and extinctions from a range of historical and recent interacting human-mediated threats. Although spending most of their time in the water, platypuses can move over land. Nevertheless, uncertainties remain whether dams are barriers to movement, thus limiting gene flow and dispersal, essential to evolution and ecology. Here we examined disruption of gene flow between platypus groups below and above five major dams, matched to four adjacent rivers without major dams. Genetic differentiation (FST) across dams was 4- to 20-fold higher than along similar stretches of adjacent undammed rivers; FST across dams was similar to differentiation between adjacent river systems. This indicates that major dams represent major barriers for platypus movements. Furthermore, FST between groups was correlated with the year in which the dam was built, increasing by 0.011 every generation, reflecting the effects of these barriers on platypus genetics. This study provides evidence of gene flow restriction, which jeopardises the long-term viability of platypus populations when groups are fragmented by major dams. Mitigation strategies, such as building of by-pass structures and translocation between upstream and downstream of the dam, should be considered in conservation and management planning

Genomics as a practical tool in sport - have we reached the starting line?

The genetic component of athletic performance approximates 50%, depending on which specific element of performance is considered. Limited genetic testing is already available commercially and genetic tests are likely to become powerful tools to improve sport performance in the future. Currently, however, selection of athletes for training squads or competition based on genomic data is premature. Larger volumes of longitudinal data within individual sports are needed to determine the efficacy of using genomic data in the management of elite athletes via manipulation of training load and diet based on personal genomic information

Reproductive Phase Locking of Mosquito Populations in Response to Rainfall Frequency

The frequency of moderate to heavy rainfall events is projected to change in response to global warming. Here we show that these hydrologic changes may have a profound effect on mosquito population dynamics and rates of mosquito-borne disease transmission. We develop a simple model, which treats the mosquito reproductive cycle as a phase oscillator that responds to rainfall frequency forcing. This model reproduces observed mosquito population dynamics and indicates that mosquito-borne disease transmission can be sensitive to rainfall frequency. These findings indicate that changes to the hydrologic cycle, in particular the frequency of moderate to heavy rainfall events, could have a profound effect on the transmission rates of some mosquito-borne diseases

Titin genotype is associated with skeletal muscle fascicle length in recreationally active men and running performance in habitually trained marathon runners

Objectives The titin gene (TTN) encodes the largest described protein to date and, due to its size, provides a molecular blueprint for the organisation and assembly of the muscle sarcomere. Differences in sarcomere length, due to the expression of different titin isoforms, have been observed previously and may influence muscle fascicle length, which could provide an advantage for running performance. Thus, the aim of this study was to investigate if the TTN rs10497520 polymorphism was associated with muscle fascicle length in recreationally active men and marathon personal best time in elite male marathon runners, and to investigate any differences in genotype frequency between RA and MR.Methods The sample comprised 278 healthy, unrelated Caucasian men who all gave written consent to take part. Participants were categorised as either recreationally active [RA; n = 137; age = 20.7 (2.7) yr; height = 1.79 (0.06) m; mass = 75.3 (10.1) kg] or marathon runners [MR; n = 141; age = 34.9 (7.8) yr; height = 1.79 (0.07) m; mass = 66.5 (6.7) kg]. MR comprised Olympic, international and national level athletes, who had all achieved marathon personal best times under 2 hr 36 mins. Resting fascicle length of the vastus lateralis muscle was assessed in vivo using B-mode ultrasonography at 50% of muscle length in RA only. All participants provided either a whole blood, saliva or buccal cell sample, from which DNA was isolated and genotyped using real-time polymerase chain reaction. Independent samples t-tests were used to determine any genotype-dependent differences in fascicle length in RA and marathon personal best time in MR. Pearson’s chi-square tests were conducted to compare genotype frequencies between RA and MR.Results Vastus lateralis fascicle length was 10.4% longer in CC homozygotes than CT heterozygotes (P = 0.003) in RA. In the absence of any TT homozygotes, reflective of the low T-allele frequency within Caucasian populations, it is unclear if fascicle length for this group would have been smaller still. No differences in genotype frequency between the RA and MR groups were observed (P = 0.500), however, within the MR group the T-allele carriers demonstrated marathon personal best times 2 min 25 s faster than CC homozygotes (P = 0.020).Conclusions These results suggest that the T-allele at rs10497520 in the TTN gene is associated with shorter skeletal muscle fascicle length and conveys an advantage for marathon running performance in habitually trained men

The interactions of physical activity, exercise and genetics and their associations with bone mineral density: implications for injury risk in elite athletes

Low bone mineral density (BMD) is established as a primary predictor of osteoporotic risk and can also have substantial implications for athlete health and injury risk in the elite sporting environment. BMD is a highly multi-factorial phenotype influenced by diet, hormonal characteristics and physical activity. The interrelationships between such factors, and a strong genetic component, suggested to be around 50–85% at various anatomical sites, determine skeletal health throughout life. Genome-wide association studies and case–control designs have revealed many loci associated with variation in BMD. However, a number of the candidate genes identified at these loci have no known associated biological function or have yet to be replicated in subsequent investigations. Furthermore, few investigations have considered gene–environment interactions—in particular, whether specific genes may be sensitive to mechanical loading from physical activity and the outcome of such an interaction for BMD and potential injury risk. Therefore, this review considers the importance of physical activity on BMD, genetic associations with BMD and how subsequent investigation requires consideration of the interaction between these determinants. Future research using well-defined independent cohorts such as elite athletes, who experience much greater mechanical stress than most, to study such phenotypes, can provide a greater understanding of these factors as well as the biological underpinnings of such a physiologically “extreme” population. Subsequently, modification of training, exercise or rehabilitation programmes based on genetic characteristics could have substantial implications in both the sporting and public health domains once the fundamental research has been conducted successfully

No association between tendon-related genes and performance in elite European Caucasian marathon runners.

Tendons adapt to load under normal physiological conditions, however, under extreme loading conditions, such as those experienced by elite endurance athletes, incomplete adaptation may occur and cause injury. The prevalence of tendinopathies in elite endurance athletes is approximately 50%, thus variability exists in an athlete's tolerance to extreme loading. A number of intrinsic and extrinsic factors contribute to modulating injury risk, some of which are modifiable and others, such as genetic variants, are non-modifiable. It was hypothesized that elite marathon runners would possess a genotype associated with enhanced tendon function, and thus protective against tendinopathy. Here, we compared the genotype frequencies of six genetic variants (COL1A1 rs1800012, VEGFA rs699947, TIMP2 rs4789932, MMP3 rs591058, MMP3 rs650108, MMP3 rs679620), previously associated with tendinopathy, in elite (men <2 h 30 min, n = 109, women <3 h 00 min, n = 99) and sub-elite (men 2 h 30 min-2 h 45 min, n = 189; women 3 h 00 min-3 h 15 min, n = 71) marathon runners with those of a non-athletic control group (n = 564). Genotype associations with marathon personal best time in the athlete group were also investigated. All participants provided either a whole blood, saliva or buccal cell sample, from which DNA was isolated, and genotyped for all six variants using real-time PCR. Genotype frequency differed between athletes and controls for TIMP2 rs4789932 (TT = 17%, CT = 51%, CC = 32% vs. TT = 22%, CT = 42%, CC = 36%, respectively; χ2 = 8.135, P = 0.017) only. However, there was no clear difference in allele frequencies between groups for TIMP2 rs4789932. MMP3 rs650108 genotype frequency differed between female elite and sub-elite athletes (χ2 = 11.913, P = 0.003) only and, as hypothesized, it was the “risk” A-allele that was ~10% less frequent in the elite, than sub-elite athletes. Following combination of all genotype data into a total genotype score, no differences in score between athletes and controls were observed (t = 2.93, P = 0.769). Similarly, no associations between total genotype score and marathon personal best time in male and female runners were observed (r ≤ 0.066, P ≥ 0.394). The results suggest elite marathon runners do not possess a genotype protective against tendinopathy, at least for the tendon-related genetic variants we investigated

Genetic Polymorphisms Related to VO2max Adaptation Are Associated With Elite Rugby Union Status and Competitive Marathon Performance

PURPOSE: Genetic polymorphisms have been associated with the adaptation to training in maximal oxygen uptake (V˙O2max). However, the genotype distribution of selected polymorphisms in athletic cohorts is unknown, with their influence on performance characteristics also undetermined. This study investigated whether the genotype distributions of 3 polymorphisms previously associated with V˙O2max training adaptation are associated with elite athlete status and performance characteristics in runners and rugby athletes, competitors for whom aerobic metabolism is important. METHODS: Genomic DNA was collected from 732 men including 165 long-distance runners, 212 elite rugby union athletes, and 355 nonathletes. Genotype and allele frequencies of PRDM1 rs10499043 C/T, GRIN3A rs1535628 G/A, and KCNH8 rs4973706 T/C were compared between athletes and nonathletes. Personal-best marathon times in runners, as well as in-game performance variables and playing position, of rugby athletes were analyzed according to genotype. RESULTS: Runners with PRDM1 T alleles recorded marathon times ∼3 minutes faster than CC homozygotes (02:27:55 [00:07:32] h vs 02:31:03 [00:08:24] h, P = .023). Rugby athletes had 1.57 times greater odds of possessing the KCNH8 TT genotype than nonathletes (65.5% vs 54.7%, χ2 = 6.494, P = .013). No other associations were identified. CONCLUSIONS: This study is the first to demonstrate that polymorphisms previously associated with V˙O2max training adaptations in nonathletes are also associated with marathon performance (PRDM1) and elite rugby union status (KCNH8). The genotypes and alleles previously associated with superior endurance-training adaptation appear to be advantageous in long-distance running and achieving elite status in rugby union