ISPAR draws together a wide range of disciplinary perspectives across the biophysical and social sciences to investigate the place of sport and physical activity in society and in relation to health and well-being, education, and sport performance.

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  • ‘We had to do intelligent thinking during recent PE’: students’ and teachers’ experiences of assessment for learning in post‐primary physical education

    MacPhail, Ann; Halbert, John (Taylor & Francis, 2010-02)
    This study arose in response to a perceived need for additional teacher support for assessment in physical education and the limited focus in physical education pedagogy literature on the impact of Assessment for Learning (AfL), in particular the impact of formative assessment on student learning. The study involved the refinement and evaluation of a post‐primary physical education planning framework with assessment instruments for use by teachers. A number of teachers were engaged in the development of assessment and planning materials, the trialling of these in school settings and their subsequent refinement based on the feedback received from the teaching and learning setting. The study was contingent on teachers cultivating a learning culture within their class. Students’ and teachers’ experiences of AfL are reported before highlighting some of the challenges that remain in investigating formative assessment.
  • Vasoreactivity before and after handgrip training in chronic heart failure patients

    Credeur, Daniel P.; Mariappan, Nithya; Francis, Joseph; Thomas, David; Moraes, Denzil; Welsch, Michael A.; University of Missouri (Elsevier, 2012-11)
    The purpose of this study was to investigate the vasodilatory and vasoconstrictor responses of the brachial artery in patients with chronic heart failure (CHF) and controls (CON) before and after a period of training and detraining.
  • The missing risk: MRI and MRS phenotyping of abdominal adiposity and ectopic fat.

    Thomas, E. Louise; Parkinson, James R.; Frost, Gary S.; Goldstone, Anthony P.; Doré, Caroline J.; McCarthy, John; Collins, Adam L.; Fitzpatrick, Julie; Durighel, Giuliana; Taylor-Robinson, Simon D.; et al. (Wiley, 2012-01)
    Individual compartments of abdominal adiposity and lipid content within the liver and muscle are differentially associated with metabolic risk factors, obesity and insulin resistance. Subjects with greater intra-abdominal adipose tissue (IAAT) and hepatic fat than predicted by clinical indices of obesity may be at increased risk of metabolic diseases despite their "normal" size. There is a need for accurate quantification of these potentially hazardous depots and identification of novel subphenotypes that recognize individuals at potentially increased metabolic risk. We aimed to calculate a reference range for total and regional adipose tissue (AT) as well as ectopic fat in liver and muscle in healthy subjects. We studied the relationship between age, body-mass, BMI, waist circumference (WC), and the distribution of AT, using whole-body magnetic resonance imaging (MRI), in 477 white volunteers (243 male, 234 female). Furthermore, we used proton magnetic resonance spectroscopy (MRS) to determine intrahepatocellular (IHCL) and intramyocellular (IMCL) lipid content. The anthropometric variable which provided the strongest individual correlation for adiposity and ectopic fat stores was WC in men and BMI in women. In addition, we reveal a large variation in IAAT, abdominal subcutaneous AT (ASAT), and IHCL depots not fully predicted by clinically obtained measurements of obesity and the emergence of a previously unidentified subphenotype. Here, we demonstrate gender- and age-specific patterns of regional adiposity in a large UK-based cohort and identify anthropometric variables that best predict individual adiposity and ectopic fat stores. From these data we propose the thin-on-the-outside fat-on-the-inside (TOFI) as a subphenotype for individuals at increased metabolic risk.
  • Telomere maintenance genes SIRT1 and XRCC6 impact age-related decline in telomere length but only SIRT1 is associated with human longevity

    Kim, Sangkyu; Bi, Xiuhua; Czarny-Ratajczak, Malwina; Dai, Jianliang; Welsh, David A.; Myers, Leann; Welsch, Michael A.; Cherry, Katie E; Arnold, Jonathan; Poon, Leonard W.; et al. (Springer, 2012-04)
    Leukocyte telomere length is widely considered a biomarker of human age and in many studies indicative of health or disease. We have obtained quantitative estimates of telomere length from blood leukocytes in a population sample, confirming results of previous studies that telomere length significantly decreases with age. Telomere length was also positively associated with several measures of healthy aging, but this relationship was dependent on age. We screened two genes known to be involved in telomere maintenance for association with the age-related decline in telomere length observed in our population to identify candidate longevity-associated genes. A single-nucleotide polymorphism located in the SIRT1 gene and another in the 3' flanking region of XRCC6 had significant effects on telomere length. At each bi-allelic locus, the minor variant was associated with longer telomeres, though the mode of inheritance fitting best differed between the two genes. No statistical interaction was detected for telomere length between the SIRT1 and XRCC6 variants or between these polymorphisms and age. The SIRT1 locus was significantly associated with longevity (P < 0.003). The frequency of the minor allele was higher in long-lived cases than in young controls, which coincides with the protective role of the minor variant for telomere length. In contrast, the XRCC6 variant was not associated with longevity. Furthermore, it did not affect the association of SIRT1 with exceptional survival. The association of the same variant of SIRT1 with longevity was near significant (P < 0.07) in a second population. These results suggest a potential role of SIRT1 in linking telomere length and longevity. Given the differences between this gene and XRCC6, they point to the distinct impact that alternate pathways of telomere maintenance may have on aging and exceptional survival.
  • Reduction of total lung capacity in obese men: comparison of total intrathoracic and gas volumes

    Watson, R.A.; Pride, N.B.; Thomas, E. Louise; Fitzpatrick, Julie; Durighel, Giuliana; McCarthy, John; Morin, Stanislas X.; Ind, P.W.; Bell, Jimmy D.; National Heart and Lung Institute; et al. (American Physiological Society, 2010-03-18)
    Restriction of total lung capacity (TLC) is found in some obese subjects, but the mechanism is unclear. Two hypotheses are as follows: 1) increased abdominal volume prevents full descent of the diaphragm; and 2) increased intrathoracic fat reduces space for full lung expansion. We have measured total intrathoracic volume at full inflation using magnetic resonance imaging (MRI) in 14 asymptomatic obese men [mean age 52 yr, body mass index (BMI) 35–45 kg/m2] and 7 control men (mean age 50 yr, BMI 22–27 kg/m2). MRI volumes were compared with gas volumes at TLC. All measurements were made with subjects supine. Obese men had smaller functional residual capacity (FRC) and FRC-to-TLC ratio than control men. There was a 12% predicted difference in mean TLC between obese (84% predicted) and control men (96% predicted). In contrast, differences in total intrathoracic volume (MRI) at full inflation were only 4% predicted TLC (obese 116% predicted TLC, control 120% predicted TLC), because mediastinal volume was larger in obese than in control [heart and major vessels (obese 1.10 liter, control 0.87 liter, P = 0.016) and intrathoracic fat (obese 0.68 liter, control 0.23 liter, P < 0.0001)]. As a consequence of increased mediastinal volume, intrathoracic volume at FRC in obese men was considerably larger than indicated by the gas volume at FRC. The difference in gas volume at TLC between the six obese men with restriction, TLC < 80% predicted (OR), and the eight obese men with TLC > 80% predicted (ON) was 26% predicted TLC. Mediastinal volume was similar in OR (1.84 liter) and ON (1.73 liter), but total intrathoracic volume was 19% predicted TLC smaller in OR than in ON. We conclude that the major factor restricting TLC in some obese men was reduced thoracic expansion at full inflation.
  • Proton magnetic resonance spectroscopy and ultrasound for hepatic fat quantification

    Mehta, Sanjeev R.; Louise Thomas, Elizabeth; Patel, Nayna; Crofton, Mary E.; McCarthy, John; Eliahoo, Joseph; Morin, Stanislas X.; Fitzpatrick, Julie; Durighel, Giuliana; Goldstone, Anthony P.; et al. (Wiley, 2010-04)
    Aim:  The increasing prevalence of fatty liver disease requires routine assessment methods. Proton magnetic resonance spectroscopy (1H MRS) is increasingly used for steatosis measurement, but due to cost, is unlikely to become a widely-used screening tool. Ultrasound is cheaper and more widely available, although subject to observer variability. Our aim was to determine the sensitivity and specificity of ultrasound against 1H MRS, using MRS as a gold standard, for the detection and quantification of hepatic fat content. Methods:  Fifty adults participated (43 men, seven women) in this study. Hepatic steatosis was assessed by ultrasound and 1H MRS. Images were graded by two independent radiologists to classify severity and distribution of liver fat. Results:  Ultrasound detected liver fat infiltration in 82% of cases measurable by 1H MRS, while liver fat was detectable in 44% of cases graded absent by ultrasound. Ultrasound grading was subjective, with the radiologists in agreement in 53% of cases (κ = 0.39, P = 0.002). Considerable overlap in intrahepatocellular lipid content was observed between different grades: absent (0.0–1.58%), mild (2.2–16.2%), moderate (4.9–26.7%) and severe (8.1–76.8%) steatosis. Ultrasound could not detect liver fat levels below 2% as measured by 1H MRS Conclusion:  Ultrasound is less sensitive than 1H MRS in detecting very low levels of liver fat content, but is sensitive to fatty infiltration greater than 2%. There is a tendency of higher ultrasound grades to correlate with higher degrees of fatty infiltration, although some overlap exists. Our findings are still consistent with ultrasound being useful as a low cost screening tool.
  • Estimation of abdominal fat compartments by bioelectrical impedance: the validity of the ViScan measurement system in comparison with MRI

    Thomas, E. Louise; Collins, Adam L.; McCarthy, John; Fitzpatrick, Julie; Durighel, Giuliana; Goldstone, Anthony P.; Bell, Jimmy D.; Imperial College, London; University of Surrey; University of Bedfordshire (Nature Publishing Group, 2010-05)
    Abdominal obesity, more specifically increased intra-abdominal adipose tissue, is strongly associated with increased risk of metabolic disease. Bioelectrical impedance analysis (BIA) has been proposed as a potential method of determining individual abdominal fat compartments in the form of the commercially available ViScan measurement system (Tanita Corporation), but it has yet to be independently validated. The objective of this study was to analyse the validity of the ViScan to assess adult abdominal adiposity across a range of body fatness.
  • Effects of handgrip training with venous restriction on brachial artery vasodilation

    Credeur, Daniel P.; Hollis, Brandon C.; Welsch, Michael A.; Louisiana State University (Wolters Kluwer/ Lippincott Williams & Wilkins, 2010-07)
    Previous studies have shown that resistance training with restricted venous blood flow (Kaatsu) results in significant strength gains and muscle hypertrophy. However, few studies have examined the concurrent vascular responses following restrictive venous blood flow training protocols.
  • Cooperation and confrontation: a macro analysis of the MediaSport institution in contemporary China

    Wu, Ping; University of Bedfordshire (Hong Kong Shue Yan University., 2012)
  • An elevation of resting metabolic rate with declining health in nonagenarians may be associated with decreased muscle mass and function in women and men, respectively.

    Kim, Sangkyu; Welsh, David A.; Ravussin, Eric; Welsch, Michael A.; Cherry, Katie E.; Myers, Leann; Jazwinski, S. Michal; Tulane University Health Sciences Center; Louisiana State University Health Sciences Center; Pennington Biomedical Research Center; et al. (Oxford University Press, 2014-06)
    Previously, we showed that FI34, a frailty index based on 34 health and function ability variables, is heritable and a reliable phenotypic indicator of healthy aging. We have now examined the relationship between major components of energy expenditure and the FI34 in participants of the Louisiana Healthy Aging Study. Resting metabolic rate was associated with FI34, even after adjustment for fat-free mass, fat mass, age, sex, thyroid hormones, and insulin-like growth factor 1 levels, in multiple regression analyses. In contrast, there was no association between total daily energy expenditure and FI34. Circulating creatine phosphokinase, a clinical marker of muscle damage, was also significantly associated with FI34. However, these associations of resting metabolic rate with FI34 were restricted to the oldest old (≥90 years) and absent in younger age groups. In oldest old men, the association of FI34 with creatine phosphokinase persisted, whereas in the oldest old women, only the association with resting metabolic rate pertained with the appearance of an effect of body size and composition. These results point toward an increasing metabolic burden for the maintenance of homeodynamics as health declines in nonagenarians, and this has implications for contraction of metabolic reserve that may potentially accelerate the path to disability.
  • Breaking up prolonged sitting time with walking does not affect appetite or gut hormone concentrations but does induce an energy deficit and suppresses postprandial glycaemia in sedentary adults

    Bailey, Daniel Paul; Broom, David R.; Chrismas, Bryna C.; Taylor, Lee; Flynn, Edward; Hough, John (NRC Research Press, 2015-12-14)
    Background: Breaking up periods of prolonged sitting can negate harmful metabolic effects but the influence on appetite and gut hormones is not understood and is investigated in this study. Methods: Thirteen sedentary (7 female) participants undertook three, 5 h trials in random order: 1) uninterrupted sitting (SIT), 2) seated with 2 min bouts of light-intensity walking every 20 min (SIT+LA), and 3) seated with 2 min bouts of moderate-intensity walking every 20 min (SIT+MA). A standardised test drink was provided at the start and an ad libitum pasta test meal provided at the end of each trial. Subjective appetite ratings and plasma acylated ghrelin, peptide YY, insulin, and glucose were measured at regular intervals. Area under the curve (AUC) was calculated for each variable. Results: AUC values for appetite and gut hormone concentrations were unaffected in the activity breaks conditions compared to uninterrupted sitting (linear mixed modelling: p>0.05). Glucose AUC was lower in SIT+MA than SIT+LA (p=0.004) and SIT (p=0.055). There was no difference in absolute ad libitum energy intake between conditions (p>0.05), however, relative energy intake was lower in SIT+LA (39%; p=0.011) and SIT+MA (120%; p<0.001) than SIT. Conclusion: Breaking up prolonged sitting does not alter appetite and gut hormone responses to a meal over a 5 h period. Increased energy expenditure from activity breaks could promote an energy deficit that is not compensated for in a subsequent meal.
  • Breaking up prolonged sitting with light-intensity walking improves postprandial glycemia, but breaking up sitting with standing does not

    Bailey, Daniel Paul; Locke, Christopher D.; University of Bedfordshire (Elsevier, 2015-05)
    Objectives: To explore the effects of breaking up prolonged sitting time with standing or light-intensity walking on a range of cardiometabolic risk markers. Design: A randomised three-period, three-treatment acute crossover trial. Methods: Ten non-obese adults took part in three trials: (1) uninterrupted sitting; (2) seated with 2-min bouts of standing every 20 min; and (3) seated with 2-min bouts of light-intensity walking every 20 min. Two standardised test drinks (total 80.3 carbohydrate, 50 g fat) were provided after an initial 1-h period of uninterrupted sitting. Plasma glucose and blood pressure were assessed hourly to calculate area under the curve. Total cholesterol, HDL, and triglycerides were assessed at baseline and 5-h. ANOVAs were used to explore between-trial differences. Results: Glucose area under the curve was lower in the activity-break condition compared to the uninterrupted sitting and standing-break conditions: mean area under the curve 18.5 (95% CI 17, 20), 22.0 (20.5, 23.5), and 22.2 (20.7, 23.7) mmol L/5-h, respectively, p < 0.001; no difference between uninterrupted sitting and standing-break conditions (p > 0.05). Systolic and diastolic blood pressure area under the curve did not differ significantly between conditions, nor did responses in lipid parameters (p > 0.05). Conclusions: This study suggests that interrupting sitting time with frequent brief bouts of light-intensity activity, but not standing, imparts beneficial postprandial responses that may enhance cardiometabolic health. These findings may have importance in the design of effective interventions to reduce cardiometabolic disease risk.
  • Appetite and gut hormone responses to moderate-intensity continuous exercise versus high-intensity interval exercise, in normoxic and hypoxic conditions

    Bailey, Daniel Paul; Smith, Lindsey Rachel; Chrismas, Bryna C.; Taylor, Lee; Stensel, David J.; Deighton, Kevin; Douglas, Jessica A.; Kerr, Catherine J.; University of Bedfordshire; Oxford Brookes University; et al. (Elsevier, 2015-06)
    This study investigated the effects of continuous moderate-intensity exercise (MIE) and high-intensity interval exercise (HIIE) in combination with short exposure to hypoxia on appetite and plasma concentrations of acylated ghrelin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). Twelve healthy males completed four, 2.6 h trials in a random order: (1) MIE-normoxia, (2) MIE-hypoxia, (3) HIIE-normoxia, and (4) HIIE-hypoxia. Exercise took place in an environmental chamber. During MIE, participants ran for 50 min at 70% of altitude-specific maximal oxygen uptake (View the MathML sourceV˙O2max) and during HIIE performed 6 × 3 min running at 90% View the MathML sourceV˙O2max interspersed with 6 × 3 min active recovery at 50% View the MathML sourceV˙O2max with a 7 min warm-up and cool-down at 70% View the MathML sourceV˙O2max (50 min total). In hypoxic trials, exercise was performed at a simulated altitude of 2980 m (14.5% O2). Exercise was completed after a standardised breakfast. A second meal standardised to 30% of participants' daily energy requirements was provided 45 min after exercise. Appetite was suppressed more in hypoxia than normoxia during exercise, post-exercise, and for the full 2.6 h trial period (linear mixed modelling, p < 0.05). Plasma acylated ghrelin concentrations were lower in hypoxia than normoxia post-exercise and for the full 2.6 h trial period (p < 0.05). PYY concentrations were higher in HIIE than MIE under hypoxic conditions during exercise (p = 0.042). No differences in GLP-1 were observed between conditions (p > 0.05). These findings demonstrate that short exposure to hypoxia causes suppressions in appetite and plasma acylated ghrelin concentrations. Furthermore, appetite responses to exercise do not appear to be influenced by exercise modality.
  • The triglyceride to high-density lipoprotein ratio identifies children who may be at risk of developing cardiometabolic disease

    Bailey, Daniel Paul; Savory, Louise A.; Denton, Sarah J.; Davies, Ben Rhys; Kerr, Catherine J.; University of Bedfordshire; Newcastle University; Oxford Brookes University; University of Bedfordshire; Newcastle University; et al. (Wiley, 2014-08)
    Aim: It is important to develop simple, reliable methods to identify high-risk individuals who may benefit from intervention. This study investigated the association between the triglyceride to high-density lipoprotein cholesterol (TG/HDL) ratio and cardiometabolic risk, cardiorespiratory fitness and physical activity in children. Methods: Anthropometric, biochemical parameters, cardiorespiratory fitness and accelerometry determined physical activity were assessed in 155 children (80 girls) from 10 to 14 years of age from Bedfordshire, UK. Participants were grouped into high and low TG/HDL ratio groups, according to published thresholds. MANCOVA and logistic regression were used in the analysis. Results: Cardiometabolic risk factor levels were significantly higher in participants with a high TG/HDL ratio (p < 0.05). The odds of having high waist circumference (OR = 13.99; 95% CI 2.93, 69.25), elevated systolic blood pressure (5.27; 1.39, 20.01), high non-HDL cholesterol (19.47; 4.42, 85.81) and ≥2 cardiometabolic risk factors (15.32; 3.10, 75.79) were higher in participants with a high TG/HDL ratio. The TG/HDL ratio values were significantly lower in those with high cardiorespiratory fitness (p = 0.01), but there was no association with physical activity. Conclusion: These findings support the use of the TG/HDL ratio to identify children with cardiometabolic risk factors who may be at risk of developing cardiometabolic disease.
  • The association between cardiorespiratory fitness and cardiometabolic risk in children is mediated by abdominal adiposity: the HAPPY study

    Bailey, Daniel Paul; Savory, Louise A.; Denton, Sarah J.; Kerr, Catherine J.; University of Bedfordshire; Newcastle University; Oxford Brookes University (Human Kinetics, 2014-10-13)
    Background: It is unclear whether cardiorespiratory fitness (CRF) is independently linked to cardiometabolic risk in children. This study investigated a) the association between CRF level and presence of cardiometabolic risk disorders using health-related cut points, and b) whether these associations were mediated by abdominal adiposity in children. Methods: This was a cross-sectional design study. Anthropometry, biochemical parameters and CRF were assessed in 147 schoolchildren (75 girls) aged 10-14 years. CRF was determined using a maximal cycle ergometer test. Children were classified as ‘fit’ or ‘unfit’ according to published thresholds. Logistic regression was used to investigate the odds of having individual and clustered cardiometabolic risk factors according to CRF level and whether abdominal adiposity mediated these associations. Results: Children classified as unfit had increased odds of presenting individual and clustered cardiometabolic risk factors (p < 0.05), but these associations no longer remained after adjusting for abdominal adiposity (p > 0.05). Conclusions: This study suggests that the association between CRF and cardiometabolic risk is mediated by abdominal adiposity in 10-14 year-old children and that abdominal adiposity may be a more important determinant of adverse cardiometabolic health in this age group.
  • Effects of exercise intensity on salivary antimicrobial proteins and markers of stress in active men

    Allgrove, Judith E.; Gomes, Elisa; Hough, John; Gleeson, Michael; Loughborough University (Taylor & Francis, 2008-04)
    In the present study, we assessed the effects of exercise intensity on salivary immunoglobulin A (s-IgA) and salivary lysozyme (s-Lys) and examined how these responses were associated with salivary markers of adrenal activation. Using a randomized design, 10 healthy active men participated in three experimental cycling trials: 50% maximal oxygen uptake ([Vdot]O2max), 75%[Vdot]O2max, and an incremental test to exhaustion. The durations of the trials were the same as for a preliminary incremental test to exhaustion (22.3 min, s x = 0.8). Timed, unstimulated saliva samples were collected before exercise, immediately after exercise, and 1 h after exercise. In the incremental exhaustion trial, the secretion rates of both s-IgA and s-Lys were increased. An increase in s-Lys secretion rate was also observed at 75%[Vdot]O2max. No significant changes in saliva flow rate were observed in any trial. Cycling at 75%[Vdot]O2max and to exhaustion increased the secretion of α-amylase and chromogranin A immediately after exercise; higher cortisol values at 75%[Vdot]O2max and in the incremental exhaustion trial compared with 50%[Vdot]O2max were observed 1 h immediately after exercise only. These findings suggest that short-duration, high-intensity exercise increases the secretion rate of s-IgA and s-Lys despite no change in the saliva flow rate. These effects appear to be associated with changes in sympathetic activity and not the hypothalamic – pituitary – adrenal axis.
  • Exercise-associated DNA methylation change in skeletal muscle and the importance of imprinted genes: a bioinformatics meta-analysis

    Brown, William Michael; University of Bedfordshire (BMJ Publishing Group Limited, 2015-03-30)
    BACKGROUND: Epigenetics is the study of processes-beyond DNA sequence alteration-producing heritable characteristics. For example, DNA methylation modifies gene expression without altering the nucleotide sequence. A well-studied DNA methylation-based phenomenon is genomic imprinting (ie, genotype-independent parent-of-origin effects). OBJECTIVE: We aimed to elucidate: (1) the effect of exercise on DNA methylation and (2) the role of imprinted genes in skeletal muscle gene networks (ie, gene group functional profiling analyses). DESIGN: Gene ontology (ie, gene product elucidation)/meta-analysis. DATA SOURCES: 26 skeletal muscle and 86 imprinted genes were subjected to g:Profiler ontology analysis. Meta-analysis assessed exercise-associated DNA methylation change. DATA EXTRACTION: g:Profiler found four muscle gene networks with imprinted loci. Meta-analysis identified 16 articles (387 genes/1580 individuals) associated with exercise. Age, method, sample size, sex and tissue variation could elevate effect size bias. DATA SYNTHESIS: Only skeletal muscle gene networks including imprinted genes were reported. Exercise-associated effect sizes were calculated by gene. Age, method, sample size, sex and tissue variation were moderators. RESULTS: Six imprinted loci (RB1, MEG3, UBE3A, PLAGL1, SGCE, INS) were important for muscle gene networks, while meta-analysis uncovered five exercise-associated imprinted loci (KCNQ1, MEG3, GRB10, L3MBTL1, PLAGL1). DNA methylation decreased with exercise (60% of loci). Exercise-associated DNA methylation change was stronger among older people (ie, age accounted for 30% of the variation). Among older people, genes exhibiting DNA methylation decreases were part of a microRNA-regulated gene network functioning to suppress cancer. CONCLUSIONS: Imprinted genes were identified in skeletal muscle gene networks and exercise-associated DNA methylation change. Exercise-associated DNA methylation modification could rewind the 'epigenetic clock' as we age. TRIAL REGISTRATION NUMBER: CRD42014009800.
  • Novel retrotransposed imprinted locus identified at human 6p25

    Zhang, Aiping; Skaar, David A.; Li, Yue; Huang, Dale; Price, Thomas M.; Murphy, Susan K.; Jirtle, Randy L. (Oxford University Press, 2011)
    Differentially methylated regions (DMRs) are stable epigenetic features within or in proximity to imprinted genes. We used this feature to identify candidate human imprinted loci by quantitative DNA methylation analysis. We discovered a unique DMR at the 50-end of FAM50B at 6p25.2. We determined that sense transcripts originating from the FAM50B locus are expressed from the paternal allele in all human tissues investigated except for ovary, in which expression is biallelic. Furthermore, an antisense transcript, FAM50B-AS, was identified to be monoallelically expressed from the paternal allele in a variety of tissues. Comparative phylogenetic analysis showed that FAM50B orthologs are absent in chicken and platypus, but are present and biallelically expressed in opossum and mouse.
  • The human imprintome: regulatory mechanisms, methods of ascertainment, and roles in disease susceptibility

    Skaar, David A.; Li, Yue; Bernal, Autumn J.; Hoyo, Cathrine; Murphy, Susan K.; Jirtle, Randy L. (National Academy of Sciences, 2012-12)
    Imprinted genes form a special subset of the genome, exhibiting monoallelic expression in a parent-of-origin-dependent fashion. This monoallelic expression is controlled by parental-specific epigenetic marks, which are established in gametogenesis and early embryonic development and are persistent in all somatic cells throughout life. We define this specific set of cis-acting epigenetic regulatory elements as the imprintome, a distinct and specially tasked subset of the epigenome. Imprintome elements contain DNA methylation and histone modifications that regulate monoallelic expression by affecting promoter accessibility, chromatin structure, and chromatin configuration. Understanding their regulation is critical because a significant proportion of human imprinted genes are implicated in complex diseases. Significant species variation in the repertoire of imprinted genes and their epigenetic regulation, however, will not allow model organisms solely to be used for this crucial purpose. Ultimately, only the human will suffice to accurately define the human imprintome.
  • Adaptive radiation-induced epigenetic alterations mitigated by antioxidants

    Bernal, Autumn J.; Dolinoy, Dana C.; Huang, Dale; Skaar, David A.; Weinhouse, Caren; Jirtle, Randy L. (Federation of American Society of Experimental Biology, 2012)
    Humans are exposed to low-dose ionizing radiation (LDIR) from a number of environmental and medical sources. In addition to inducing genetic mutations, there is concern that LDIR may also alter the epigenome. Such heritable effects early in life can either be positively adaptive or result in the enhanced formation of diseases, including cancer, diabetes, and obesity. Herein, we show that LDIR significantly increased DNA methylation at the viable yellow agouti (A(vy)) locus in a sex-specific manner (P=0.004). Average DNA methylation was significantly increased in male offspring exposed to doses between 0.7 and 7.6 cGy, with maximum effects at 1.4 and 3.0 cGy (P<0.01). Offspring coat color was concomitantly shifted toward pseudoagouti (P<0.01). Maternal dietary antioxidant supplementation mitigated both the DNA methylation changes and coat color shift in the irradiated offspring. Thus, LDIR exposure during gestation elicits epigenetic alterations that lead to positive adaptive phenotypic changes that are negated with antioxidants, indicating they are mediated in part by oxidative stress. These findings provide evidence that in the isogenic A(vy) mouse model, epigenetic alterations resulting from LDIR play a role in radiation hormesis, bringing into question the assumption that every dose of radiation is harmful.

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