Acute myeloid leukemia (AML) is a clonal disorder of the blood forming cells characterized by accumulation of immature blast cells in the bone marrow and peripheral blood. Being a heterogeneous disease, AML has been the subject of numerous studies that focus on unraveling the clinical, cellular and molecular variations with the aim to better understand and treat the disease. Cytogenetic-risk stratification of AML is well established and commonly used by clinicians in therapeutic management of cases with chromosomal abnormalities. Successive inclusion of novel molecular abnormalities has substantially modified the classification and understanding of AML in the past decade. With the advent of next generation sequencing (NGS) technologies the discovery of novel molecular abnormalities has accelerated. NGS has been successfully used in several studies and has provided an unprecedented overview of molecular aberrations as well as the underlying clonal evolution in AML. The extended spectrum of abnormalities discovered by NGS is currently under extensive validation for their prognostic and therapeutic values. In this review we highlight the recent advances in the understanding of AML in the NGS era.

BackgroundPreterm birth (PTB), birth at <37 weeks of gestation, is a significant global public health problem. World-wide, about 15 million babies are born preterm each year resulting in more than a million deaths of children. Preterm neonates are more prone to problems and need intensive care hospitalization. Health issues may persist through early adulthood and even be carried on to the next generation. Majority (70 %) of PTBs are spontaneous with about a half without any apparent cause and the other half associated with a number of risk factors. Genetic factors are one of the significant risks for PTB. The focus of this review is on single nucleotide gene polymorphisms (SNPs) that are reported to be associated with PTB.ResultsA comprehensive evaluation of studies on SNPs known to confer potential risk of PTB was done by performing a targeted PubMed search for the years 2007–2015 and systematically reviewing all relevant studies. Evaluation of 92 studies identified 119 candidate genes with SNPs that had potential association with PTB. The genes were associated with functions of a wide spectrum of tissue and cell types such as endocrine, tissue remodeling, vascular, metabolic, and immune and inflammatory systems.ConclusionsA number of potential functional candidate gene variants have been reported that predispose women for PTB. Understanding the complex genomic landscape of PTB needs high-throughput genome sequencing methods such as whole-exome sequencing and whole-genome sequencing approaches that will significantly enhance the understanding of PTB. Identification of high risk women, avoidance of possible risk factors, and provision of personalized health care are important to manage PTB.

BackgroundComparative analysis of tissue-specific transcriptomes is a powerful technique to uncover tissue functions. Our FlyAtlas.org provides authoritative gene expression levels for multiple tissues of Drosophila melanogaster (1). Although the main use of such resources is single gene lookup, there is the potential for powerful meta-analysis to address questions that could not easily be framed otherwise. Here, we illustrate the power of data-mining of FlyAtlas data by comparing epithelial transcriptomes to identify a core set of highly-expressed genes, across the four major epithelial tissues (salivary glands, Malpighian tubules, midgut and hindgut) of both adults and larvae.MethodParallel hypothesis-led and hypothesis-free approaches were adopted to identify core genes that underpin insect epithelial function. In the former, gene lists were created from transport processes identified in the literature, and their expression profiles mapped from the flyatlas.org online dataset. In the latter, gene enrichment lists were prepared for each epithelium, and genes (both transport related and unrelated) consistently enriched in transporting epithelia identified.ResultsA key set of transport genes, comprising V-ATPases, cation exchangers, aquaporins, potassium and chloride channels, and carbonic anhydrase, was found to be highly enriched across the epithelial tissues, compared with the whole fly. Additionally, a further set of genes that had not been predicted to have epithelial roles, were co-expressed with the core transporters, extending our view of what makes a transporting epithelium work. Further insights were obtained by studying the genes uniquely overexpressed in each epithelium; for example, the salivary gland expresses lipases, the midgut organic solute transporters, the tubules specialize for purine metabolism and the hindgut overexpresses still unknown genes.ConclusionTaken together, these data provide a unique insight into epithelial function in this key model insect, and a framework for comparison with other species. They also provide a methodology for function-led datamining of FlyAtlas.org and other multi-tissue expression datasets.

Epigenetic modification refers to heritable changes in gene function that cannot be explained by alterations in the DNA sequence. The current literature clearly demonstrates that the epigenetic response is highly dynamic and influenced by different biological and environmental factors such as aging, nutrient availability and physical exercise. As such, it is well accepted that physical activity and exercise can modulate gene expression through epigenetic alternations although the type and duration of exercise eliciting specific epigenetic effects that can result in health benefits and prevent chronic diseases remains to be determined. This review highlights the most significant findings from epigenetic studies involving physical activity/exercise interventions known to benefit chronic diseases such as metabolic syndrome, diabetes, cancer, cardiovascular and neurodegenerative diseases.

BackgroundCardiorespiratory fitness (VO2max) is an excellent predictor of chronic disease morbidity and mortality risk. Guidelines recommend individuals undertake exercise training to improve VO2max for chronic disease reduction. However, there are large inter-individual differences between exercise training responses. This systematic review is aimed at identifying genetic variants that are associated with VO2max trainability.MethodsPeer-reviewed research papers published up until October 2016 from four databases were examined. Articles were included if they examined genetic variants, incorporated a supervised aerobic exercise intervention; and measured VO2max/VO2peak pre and post-intervention.ResultsThirty-five articles describing 15 cohorts met the criteria for inclusion. The majority of studies used a cross-sectional retrospective design. Thirty-two studies researched candidate genes, two used Genome-Wide Association Studies (GWAS), and one examined mRNA gene expression data, in addition to a GWAS. Across these studies, 97 genes to predict VO2max trainability were identified. Studies found phenotype to be dependent on several of these genotypes/variants, with higher responders to exercise training having more positive response alleles than lower responders (greater gene predictor score). Only 13 genetic variants were reproduced by more than two authors. Several other limitations were noted throughout these studies, including the robustness of significance for identified variants, small sample sizes, limited cohorts focused primarily on Caucasian populations, and minimal baseline data. These factors, along with differences in exercise training programs, diet and other environmental gene expression mediators, likely influence the ideal traits for VO2max trainability.ConclusionNinety-seven genes have been identified as possible predictors of VO2max trainability. To verify the strength of these findings and to identify if there are more genetic variants and/or mediators, further tightly-controlled studies that measure a range of biomarkers across ethnicities are required.

BackgroundThere has been considerable growth in basic knowledge and understanding of how genes are influencing response to exercise training and predisposition to injuries and chronic diseases. On the basis of this knowledge, clinical genetic tests may in the future allow the personalisation and optimisation of physical activity, thus providing an avenue for increased efficiency of exercise prescription for health and disease.ResultsThis review provides an overview of the current status of genetic testing for the purposes of exercise prescription and injury prevention. As such there are a variety of potential uses for genetic testing, including identification of risks associated with participation in sport and understanding individual response to particular types of exercise. However, there are many challenges remaining before genetic testing has evidence-based practical applications; including adoption of international standards for genomics research, as well as resistance against the agendas driven by direct-to-consumer genetic testing companies. Here we propose a way forward to develop an evidence-based approach to support genetic testing for exercise prescription and injury prevention.ConclusionBased on current knowledge, there is no current clinical application for genetic testing in the area of exercise prescription and injury prevention, however the necessary steps are outlined for the development of evidence-based clinical applications involving genetic testing.