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Despite numerous attempts to discover genetic variants associated with elite athletic performance, an individual's trainability and injury predisposition, there has been limited progress to date. Past reliance on candidate gene studies focusing predominantly on genotyping a limited number of genetic variants in small, often heterogeneous cohorts has not generated results of practical significance. Hypothesis-free genome-wide approaches will in the future provide more comprehensive coverage and in-depth understanding of the biology underlying sports-related traits and related genetic mechanisms. Large, collaborative projects with sound experimental designs (e.g. clearly defined phenotypes, considerations and controls for sources of variability, and necessary replications) are required to produce meaningful results, especially when a hypothesis-free approach is used. It remains to be determined whether the novel approaches under current implementation will result in findings with real practical significance. This review will briefly summarize current and future directions in exercise genetics and genomics. Sin financiación No data JCR 2016 0.609 SJR (2016) Q2, 98/240 Orthopedics and Sports Medicine, 59/169 Physical Therapy, Sports Therapy and Rehabilitation; Q3, 69/128 Sports Science No data IDR 2016 UEM

Erratum to: Eur J Appl Physiol (2014) 114:2625–2634 DOI 10.1007/s00421-014-2986-7 Unfortunately, one of the affiliations of the co-author, Alun G. Williams, has been missed in the original publication of the article. The correct information is as follows: Alun G. Williams Institute for Performance Research, Manchester Metropolitan University, Crewe CW1 5DU, UK

Introduction: Inter-individual variability in measurements of muscle strength and its determinants was identified to: (1) produce a normative data set describing the normal range and (2) determine whether some measurements are more informative than others when evaluating inter-individual differences. Methods: Functional and morphological characteristics of the vastus lateralis were measured in 73 healthy, untrained adult men. Results: Inter-individual variability (coefficient of variation) was greater for isometric maximal voluntary contraction (MVC) torque (18.9%) compared with fascicle force (14.6%; P = 0.025) and physiological cross-sectional area (PCSA; 17.2%) compared with anatomical cross-sectional area (ACSA, 13.0%; P

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.

Introduction: Muscle weakness is present in the paretic limbs of individuals with cerebral palsy (CP). We aimed to determine what neuromuscular factors contribute to weakness in adults with CP during isometric maximal voluntary contractions (iMVCs). Methods: Gastrocnemius anatomical cross-sectional area (ACSA) and agonist and antagonist activation were measured in 11 CP and 11 control adult men during plantarflexion iMVC. Results: Plantarflexion iMVC torque of the paretic leg was 42% and 52% less than in the non-paretic and control limbs, respectively. The paretic gastrocnemius ACSA was smaller than in the control group only. Paretic agonist activation was less than the non-paretic and control groups, whereas antagonist coactivation was higher. Multiple regression analysis revealed muscle activation accounted for 57% of variation in paretic plantarflexion iMVC torque. Conclusions: In individuals with CP, muscle weakness in the paretic limb is attributed primarily to impaired neural activation and, to a lesser degree, ACSA.

5.410 JCR (2013) Q1, 22/164 Genetics & heredity UEM

This study investigated association between polymorphisms of α-actinin-3 (ACTN3) and vitamin D receptor (VDR) genes, and the skeletal muscle phenotypes; sprint performance, jump capacity, and knee extensor and flexor strength. Sixty-two non-resistance trained Caucasian females (mean ± SD; 21 ± 4 years) completed 15 m sprint, standing vertical jump, knee extensor and flexor isometric maximal voluntary contraction (MVC) tests. 15 m sprint and vertical jump were assessed using infrared timing gates and a piezoelectric force platform respectively, with knee extensor and flexor strength assessed using isokinetic dynamometry. ACTN3 R577X and VDR BsmI polymorphisms were determined using real-time polymerase chain reaction (PCR). A one-way analysis of variance (ANOVA) was used to examine differences between skeletal muscle phenotypes for the ACTN3 and VDR genotypes. 15 m sprint(ACTN3: RR = 2.87 ± 0.17 s, RX = 2.92 ± 0.22 s, XX = 2.95 ± 0.17 s, P = 0.384; VDR: bb = 2.86 ± 0.14 s, Bb = 2.96 ± 0.23 s, BB = 2.85 ± 0.21 s, P = 0.194) and standing vertical jump performance (ACTN3 P = 0.112; VDR P = 0.788) were not associated with ACTN3 or VDR genotypes. Neither was any association found between knee extensor MVC and ACTN3 (P = 0.120) or VDR genotypes (P = 0.978), or between knee flexor MVC and ACTN3 (P = 0.852) or VDR genotypes (P = 0.718). The ACTN3 R577X and VDR BsmI polymorphisms do not appear to substantially influence the function of skeletal muscle in Caucasian females.

Considerable variability exists between people in their health- and performance-related adaptations to conventional endurance training. We hypothesized that some of this variability might be due to differences in the training stimulus received by the working muscles. In 71 young sedentary women we observed large variations in the ratio of one-leg cycling muscle aerobic capacity (V(O2peak)) to two-leg cycling whole-body maximal oxygen uptake (V(O2max); Ratio(1:2); range 0.58-0.96). The variability in Ratio(1:2) was primarily due to differences between people in one-leg V(O2peak) (r = 0.71, P < 0.0005) and was not related to two-leg V(O2max) (r = 0.15, P = 0.209). Magnetic resonance imaging (n = 30) and muscle biopsy sampling (n = 20) revealed that one-leg V(O2peak) was mainly determined by muscle volume (r = 0.73, P < 0.0005) rather than muscle fibre type or oxidative capacity. A high one-leg V(O2peak) was associated with favourable lipoprotein profiles (P = 0.033, n = 24) but this was not the case for two-leg V(O2max). Calculations based on these data suggest that conventional two-leg exercise at 70% V(O2max) requires subjects with the lowest Ratio(1:2) to work their legs at 60% of single-leg V(O2peak), whilst those with the highest Ratio(1:2) work their legs at only 36% of maximum. It was concluded that endurance training carried out according to current guidelines will result in highly variable training stimuli for the leg muscles and variable magnitudes of adaptation. These conclusions have implications for the prescription of exercise to improve health and for investigations into the genetic basis of muscle adaptations.

Regular endurance training increases skeletal muscle aerobic capacity, but there is considerable variability between individuals in the magnitude of the training response. The present study investigated inter-individual variability in adaptations of enzymes involved in fatty acid and glucose metabolism. The local ethics committee approved the study and 20 untrained young women gave written informed consent to participate. Biopsies were obtained from the vastus lateralis muscle before and after six weeks of endurance cycle training (3 x 45 min sessions/wk). Western blot analyses were used to measure the expression of a) the mitochondrial enzymes succinate dehydrogenase (SDH), cytochrome C oxidase (COX1) and ATP synthase (ATPsyn); b) the proteins involved in fatty acid metabolism 3-hydroxyacyl CoA dehydrogenase (HAD) and transporter CD36 (CD36) and c) those involved in glucose metabolism; phosphofructokinase (PFK) and glucose transporter 4 (GLUT4). As the data were not normally distributed non-parametric statistical tests were used. The maximal oxygen uptake (10%) and protein expression of SDH (47%), COX1 (52%), ATPsyn (63%), HAD (69%) and CD36 (86%) were all significantly elevated (all P < 0.05), while PFK (29%) and GLUT4 (18%) did not change with training. There was, however, considerable inter-individual variability in training response of each protein and this was examined in relation to the delta SDH, since fatty acid and glucose metabolism converge in the mitochondria. Delta SDH correlated with the training-induced changes in COX1 (r = 0.63), HAD (r = 68), CD36 (r = 0.85), PFK (r = 0.86) and GLUT4 (r = 0.80) (all P < 0.01), but not with delta ATPsyn (r = 0.38, P = 0.099). High and Low groups (n = 6 per group) were classified as those individuals having a delta SDH in the upper or lower third, respectively, of the mean of the group as a whole. The absence of a significant group x protein interaction (repeated measures ANOVA) indicated that the changes in expression of enzymes involved in fatty acid and glucose metabolism showed similar responses within groups, but different responses between groups (Fig. 1). This was also true if delta COX1 was used instead of delta SDH as a marker of mitochondrial adaptations. In conclusion, the data indicate a coordinated response of mitochondrial enzymes and proteins associated with fat metabolism in response to endurance training. The variable response between individuals may indicate genetic differences in the coordinating signal(s).

The British Association of Sport and Exercise Sciences (BASES) Molecular Exercise Physiology Interest Group has produced a position stand to advise on ethical and other issues associated with genetic research in sport and exercise science. This article is an updated summary of the position stand. The heritability of sport and exercise-related traits such as maximal oxygen uptake, muscle fibre composition and trainability is often approximately 50%. Little is known about the variations in DNA responsible and a major aim of current research is to identify the variations in DNA (or genetic loci) that determine heritable traits. Identifying the genetic loci will also inform us about the mechanisms that regulate a trait and could be used to develop applications such as genetic performance tests or genetic screens for individuals at high risk of sudden death during sport, for example, due to a gene mutation related to cardiac function. Another application could be to use genetic tests to prescribe personalised training or exercise therapy programmes for athletes or patients, respectively. Serious ethical concerns are associated with genetic testing especially when such testing is performed on embryos or minors, requested by others such as parents, coaches or physicians and when it is used to discriminate against athletes, for example by selecting squad athletes on the basis of genetic performance tests. Recommendations from the position stand include: (i) Scientists should be aware of the ethical implications of their work and engage knowledgably in public debates; (ii) genetic testing in the sport and exercise context (with the possible exception of preparticipation risk screening) should be confined to mature individuals who fully understand the relevant issues and a system of counselling should be introduced; (iii) pre-participation genetic risk screening should not be obligatory and the confidentiality of such testing should be ensured.

Human physical capability is influenced by many environmental and genetic factors, and it is generally accepted that physical capability phenotypes are highly polygenic. However, the ways in which relevant polymorphisms combine to influence the physical capability of individuals and populations are unknown. Initially, the literature was searched to identify associations between 23 genetic polymorphisms and human endurance phenotypes. Next, typical genotype frequencies of those polymorphisms in the general population were obtained from suitable literature. Using probability calculations, we found only a 0.0005% chance of a single individual in the world having the 'preferable' form of all 23 polymorphisms. As the number of DNA variants shown to be associated with human endurance phenotypes continues to increase, the probability of any single individual possessing the 'preferable' form of each polymorphism will become even lower. However, with population turnover, the chance of such genetically gifted individuals existing increases. To examine the polygenic endurance potential of a human population, a 'total genotype score' (for the 23 polymorphisms) was calculated for each individual within a hypothetical population of 1000 000. There was considerable homogeneity in terms of genetic predisposition to high endurance potential, with 99% of people differing by no more than seven genotypes from the typical profile. Consequently, with population turnover world and Olympic records should improve even without further enhancement of environmental factors, as more 'advantageous' polygenic profiles occasionally, though rarely, emerge. More broadly, human potential appears limited by the similarity of polygenic profiles at both the 'elite sport' and 'chronic disorder' ends of the performance continuum.

Purpose: The D-variant of the angiotensin-1 converting enzyme (ACE) gene is associated with higher circulating and tissue ACE activity. Some studies have suggested a similar association of genotype with muscle strength or the gain in strength in response to training. This study has assessed the relationship between circulating ACE activity, strength, and the response to training. Methods: Eighty-one untrained men were tested for quadriceps muscle strength, and 44 of these performed an 8-wk program of dynamic strength training of the quadriceps muscle group. Venous blood was obtained for assessment of circulating ACE activity before and after the training program. ACE genotype was also determined. Results: At baseline, circulating ACE activity was significantly correlated with isometric (r = 0.25-0.29, P < 0.02) and isokinetic (r = 0.38, P < 0.0005) quadriceps muscle strength. ACE genotype also seemed to be related to pretraining muscle strength. However, circulating ACE activity showed no significant association with the 9-14% mean increases of muscle strength in response to the training intervention. ACE genotype also showed no association with the training-induced change in muscle strength. Circulating ACE activity did not change significantly after the training program. Conclusions: The data support a role for ACE in the regulation of human skeletal muscle strength, but do not confirm a role in altering the response to short-term training.

To explore the possibility of training diagnosis for a 3.2-km loaded march with a 25 kg load, 50 men trained for 10 weeks using either running, marching, and endurance- based circuit training (Circuits), or running, marching, and resistance training (Resistance). The march was performed before and after training, and other measurements related to loaded marching were conducted before training only. Each group was ranked by improvement in the loaded march, and divided into significantly different subgroups of 'good' and 'poor' responders (improvements of approximately 20% vs. 10%). For Circuits, there were significant differences between good and poor responders to training in the pretraining ratios of shuttle run: isometric lift strength (p 5 0.031) and shuttle run: isometric back extension strength (p 5 0.033). Stronger subjects with lower endurance responded better to Circuits. Resistance tended to show the opposite effect (p , 0.2). These are the first objective data on which to prescribe training for load carriage on an individual basis.

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.