Genome-environment Interactions Research Articles

Genomics in school

School curricula always lag behind scientific innovations; modern science has made so many great advances that the quantity of ‘basic’ science to be taught in the classroom increases year on year. Major breakthroughs and new research are obvious in a range of scientific disciplines, including medicine, forensics, biofuels, vaccine research and the mitigation of pollution (NGI, 2006). Moreover, fundamental biological concepts and practices have themselves advanced and school curricula need to be revised; for example, in evolutionary biology (Moore, 2007), probable evolutionary relationships are now being constructed by comparing proteins and genome sequences between organisms, rather than by searching for similarities in anatomy, embryology and physiology. > …modern science has made so many great advances that the quantity of ‘basic’ science to be taught in the classroom increases year on year The conceptual and practical changes that have taken place in scientific theory and research in relation to genomics have also not yet found their place in the science curriculum, at least not in the Netherlands. It is now a few years since the publication of the human genome, and genomics research is continually generating large and complex data sets that have transformed the study of virtually all life processes (Collins, 2003). Despite this, and although a range of outreach programmes offer a temporary solution, such as the Dutch ‘mobile DNA labs’ (van Mil, 2007), greater efforts are needed to embed genomics into the standard science curriculum. Two important characteristics of genomics are immediately apparent for inclusion in new educational materials. First, genomics combines the expertise and techniques of many disciplines—for example, molecular biology, physical sciences and bioinformatics—in order to study genome–environment interactions in relation to phenomena at many biological levels from the molecular up to that of patient communities or ecosystems. Second, genomics research programmes are often accompanied by studies …

Sobre el origen ontogénico del ser humano: La solución científica

Every living being is the result of a genome-environment interaction. Neither human oocytes nor spermatozoids have human functional genomes, but the zygote that they constitute may have a human functional genome and other functional genomes such as those of the hydatidiform mole, polyploids, and non-human living beings. When the zygotic human functional genome is integrated and activated, the biotic humanity is acquired. This may occur when the paternal chromatin decondenses; the nuclear environment and envelope of both nuclei are changed to constitute pronuclei; the replacement of sperm protamines by histones; genome imprinting modifications; centriole duplication; and more importantly, the fourfold genome replication. Other propositions on the origin of humans are: embryo implantation [6-7 days post fertilization, (dpf)]; the appearance of the antero-posterior axis; the limit for monozygote twining (13dpf) and the appearance of the neural tissue (16dpf). They are refuted because some mammals do not implant; embryo axes are present in the zygote; some animals regenerate complete individuals from each part in which they are divided; plants do not have neural system; a human whose brain was destroyed by cancer continues to be a human. Alternative propositions coming from philosophies, theologies, perceptive knowledge, beliefs and intuitions and based on conceptualizations like person, anima, soul, organization, socio-cultural relations are ideologically or religiously biased and based on irreducible beliefs such as faith. They lead to disagreement rather than to agreement.

From genomics to chemical genomics: new developments in KEGG

The increasing amount of genomic and molecular information is the basis for understanding higher-order biological systems, such as the cell and the organism, and their interactions with the environment, as well as for medical, industrial and other practical applications. The KEGG resource () provides a reference knowledge base for linking genomes to biological systems, categorized as building blocks in the genomic space (KEGG GENES) and the chemical space (KEGG LIGAND), and wiring diagrams of interaction networks and reaction networks (KEGG PATHWAY). A fourth component, KEGG BRITE, has been formally added to the KEGG suite of databases. This reflects our attempt to computerize functional interpretations as part of the pathway reconstruction process based on the hierarchically structured knowledge about the genomic, chemical and network spaces. In accordance with the new chemical genomics initiatives, the scope of KEGG LIGAND has been significantly expanded to cover both endogenous and exogenous molecules. Specifically, RPAIR contains curated chemical structure transformation patterns extracted from known enzymatic reactions, which would enable analysis of genome-environment interactions, such as the prediction of new reactions and new enzyme genes that would degrade new environmental compounds. Additionally, drug information is now stored separately and linked to new KEGG DRUG structure maps.

The future of microarray technology: networking the genome search

In recent years microarray technology has been increasingly used in both basic and clinical research, providing substantial information for a better understanding of genome-environment interactions responsible for diseases, as well as for their diagnosis and treatment. However, in genomic research using microarray technology there are several unresolved issues, including scientific, ethical and legal issues. Networks of excellence like GA(2)LEN may represent the best approach for teaching, cost reduction, data repositories, and functional studies implementation.

Genome–environment interactions in the molecular pathogenesis of dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is a heart muscle disease characterized by impaired contractility and dilation of the ventricles. In a subset of DCM patients, classical inheritance patterns occur (familial DCM), which have led to the identification of specific genomic loci and gene defects causing monogenic DCM subtypes. In the majority of DCM patients, however, there is no evidence for a monogenic etiology of the disorder (sporadic DCM), and in the absence of other recognizable etiological factors, these cases were classified as "idiopathic". Recent research suggests that cardiotropic viruses are important environmental factors in the pathogenesis of "idiopathic" cases and that DCM commonly results from interactions between genetic and environmental factors, whereas "pure" genetic forms are rather rare. Regarding genetics, the clinical cardiomyopathic phenotype associated with single gene defects may be highly variable for unknown reasons. Furthermore, a novel class of genetic defects was identified recently which provide a molecular basis for abnormal reactions of cardiomyocytes to environmental stress. These defects are paradigms of specific molecular links between genome and environment during the pathogenesis of DCM. Regarding environmental factors, a recent molecular virological study based on myocardial biopsies in a large series of sporadic DCM patients has detected cardiac viral infections in the majority of patients, with a broad spectrum of virus species being involved. Apparently, DCM does not only occur as a late sequela of acute viral myocarditis, but also in patients without clinical history of cardiac viral disease. Cardiotropic viruses thus emerge as prevalent environmental factors which may cause or influence the course of DCM in a large fraction of cases. Synopsis of current data suggests that a comprehensive picture of DCM pathogenesis can only be drawn if both genetic and environmental pathogenetic factors are considered. The course of cardiac viral infections depends strongly on genetic host factors and may range from rapid and complete virus elimination or silencing without clinical symptoms, to rapidly progressive or fatal disease. Viruses interact not only with genetically heterogenous host systems of virus uptake, migration, and antiviral immunity, but, due to their prevalence in DCM hearts, are also likely to encounter multiple structural proteins of cardiac cells known to be defective in familial DCM. The combined knowledge on DCM-associated gene defects and viruses therefore suggests in-depth studies on genome-environment interactions in DCM pathogenesis which may underlie the high clinical variability observed both in monogenic and virus-associated DCM and have implications for the clinical management of DCM patients.

Inherited and acquired interactions between ACHE and PON1 polymorphisms modulate plasma acetylcholinesterase and paraoxonase activities

The 5.5 Mb chromosome 7q21-22 ACHE/PON1 locus harbours the ACHE gene encoding the acetylcholine hydrolyzing, organophosphate (OP)-inhibitable acetylcholinesterase protein and the paraoxonase gene PON1, yielding the OP-hydrolyzing PON1 enzyme which also displays arylesterase activity. In search of inherited and acquired ACHE-PON1 interactions we genotyped seven polymorphic sites and determined the hydrolytic activities of the corresponding plasma enzymes and of the AChE-homologous butyrylcholinesetrase (BChE) in 157 healthy Israelis. AChE, arylesterase, BChE and paraoxonase activities in plasma displayed 5.4-, 6.5-, 7.2- and 15.5-fold variability, respectively, with genotype-specific differences between carriers of distinct compound polymorphisms. AChE, BChE and arylesterase but not paraoxonase activity increased with age, depending on leucine at PON1 position 55. In contrast, carriers of PON1 M55 displayed decreased arylesterase activity independent of the - 108 promoter polymorphism. Predicted structural consequences of the PON1 L55M substitution demonstrated spatial shifts in adjacent residues. Molecular modelling showed substrate interactions with the enzyme variants, explaining the changes in substrate specificity induced by the Q192R substitution. Intriguingly, PON1, but not BChE or arylesterase, activities displayed inverse association with AChE activity. Our findings demonstrate that polymorphism(s) in the adjacent PON1 and ACHE genes affect each other's expression, predicting for carriers of biochemically debilitating ACHE/PON1 polymorphisms adverse genome-environment interactions.

Genetic modules and networks for behavior: lessons from Drosophila

Behaviors are quantitative traits determined through actions of multiple genes and subject to genome-environment interactions. Early studies concentrated on analyzing the effects of single genes on behaviors, often generating views of simplified linear genetic pathways. The genome era has generated a profound paradigm shift enabling us to identify all the genes that contribute to expression of a behavioral phenotype, to investigate how they are organized as functional ensembles and to begin to identify polymorphisms that contribute to phenotypic variation and are targets for natural selection. Recent studies show that the genetic architecture of behavior is determined by dynamic and plastic modular networks of pleiotropic genes and that the behavioral phenotype manifests itself as an emergent property of such networks. Such networks are exquisitely sensitive to genetic background and sex effects. This review describes how Drosophila can serve as a model for uncovering fundamental principles of the genetic architecture of behavior.

Radioadaptive response and genomic instability: a phenotypic dichotomy of genome–environment interaction

There emerged an upsurge of concern on the diverse cellular response to radiation which was new to the existing paradigm of radiobiology. They include adaptive response, genomic instability, bystander effect, pseudocytokine effect and apoptosis. Their molecular mechanism and health consequences are largely unknown. However, accumulated data indicate that they are all cellular manifestations of programmed adaptive mechanism intrinsic to the organisms for the existence of life either by epistatic response to minimize the negative impact (adaptive response) or by remodeling their genome (genomic instability). The cells have efficient damage sensing and signaling mechanisms for dose-dependent blanching cooperated by protein kinase C (PKC), p38 mitogen-activated protein kinase (p38MAPK) and phospholipase C (PLC) with p53 protein as a downstream effector. The signals are transferred to the bystander cells for orchestrated response. For the adaptive response to have an effect in vivo, two hits must be present within a limited time in a cell or a mass of bystander cells. This determines a minimum effective dose rate, below which remodeling of genome in tissue by apoptotic removal of cells with potentially genotoxic damage may be the prevailing mechanism for modulating radiation effect. Dose refractoriness of chromosome aberrations of stem cell origin in human low dose-rate exposures is consistent with this model.

Common components, networks, and pathways of cross-tolerance to stress. The central role of "redox" and abscisic acid-mediated controls.

The vigor and responsiveness of plants to environmental stress result from the constant re-adjustment of physiology and metabolism throughout the life cycle within the framework of the genetic background. Plants have developed unique strategies for responding to ever-changing environmental conditions, exhaustively monitoring their surroundings and adjusting their metabolic systems to maintain homeostasis. The severity of stress, the genetic background of the plant, and its individual history determine everyday survival or death. These factors dictate the destiny of any individual. The genomeenvironment interaction is, therefore, an essential focus for the elucidation of the nature of the phenotypic variation leading to the successful response of plants to environmental cues. Plants acclimate to biotic and abiotic stresses by triggering a cascade or network of events that starts with stress perception and ends with the expression of a battery of target genes. The key components of the stress-response relationship are illustrated in Fig. 1. These are stress stimulus, signals, transducers, transcription regulators, target genes, and stress responses, including morphological, biochemical, and physiological changes. In evolutionary terms, components that are near to the end of the stressresponse cascade are not predicted to be the ones whose actions significantly affect the operation of other genes. However, factors that act at early stages are critical for other cell functions. Plants make use of common pathways and components in the stressresponse relationship. This phenomenon, which is known as cross-tolerance, allows plants to adapt/ acclimate to a range of different stresses after exposure to one specific stress. The major focus of this review, therefore, concerns the basic features of signaling that underpin cross-tolerance and result from the action of common elements, which are likely to occur early in the stress response cascade. First, using drought and chilling as examples, we explore the evidence for common signals and elements that confer cross-tolerance. Second, we highlight the importance of “redox signals” in such networks and discuss the evidence to date for the existence of such pathways in plants. The elucidation of common components has enormous potential and has, therefore, become a priority in research and breeding programs aimed at improving plant stress tolerance.

Identifying critical windows of exposure for children's health.

Several authors have considered the importance of exposure timing and how this affects the outcomes observed, but no one has systematically compiled preconceptional, prenatal, and postnatal developmental exposures and subsequent outcomes. Efforts were undertaken to examine the information available and to evaluate implications for risk assessment for several areas: a) respiratory and immune systems, b) reproductive system, c) nervous system, d) cardiovascular system, endocrine system, and general growth, and e) cancer. Major conclusions from a workshop on "Critical Windows of Exposure for Children's Health" included a) broad windows of sensitivity can be identified for many systems but detailed information is limited; b) cross-species comparisons of dose to target tissue and better data on the exposure-dose-outcome continuum are needed; c) increased interaction among scientific disciplines can further understanding by using laboratory animal results in designing epidemiological studies and human data to suggest specific laboratory studies on mechanisms and agent-target interactions; and d) thus far, only limited attention has been given to peripubertal/adolescent exposures, adult consequences of developmental exposures, and genome-environment interactions. More specific information on developmental windows will improve risk assessment by identifying the most sensitive window(s) for evaluation of dose-response relationships and exposure, evaluation of biological plausibility of research findings in humans, and comparison of data across species. In public health and risk management, information on critical windows may help identify especially susceptible subgroups for specific interventions.