Epigenetics And The Environment Emerging Patterns And Implications Pdf

epigenetics and the environment emerging patterns and implications pdf

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Transposable elements TEs are genomic parasites that selfishly replicate at the expense of host fitness. Fifty years of evolutionary studies of TEs have concentrated on the deleterious genetic effects of TEs, such as their effects on disrupting genes and regulatory sequences. Host genomes typically silence TEs by the deposition of repressive epigenetic marks.

Epigenetics is the study of heritable changes in gene expression active versus inactive genes that do not involve changes to the underlying DNA sequence — a change in phenotype without a change in genotype — which in turn affects how cells read the genes.


Metrics details. As epigenetic studies become more common and lead to new insights into health and disease, the return of individual epigenetic results to research participants, in particular in large-scale epigenomic studies, will be of growing importance.

Major challenges include how to determine the clinical validity and actionability of epigenetic results, and considerations related to environmental exposures and epigenetic marks, including circumstances warranting the sharing of results with family members and third parties. Interdisciplinary collaboration and good public communication regarding epigenetic risk will be important to advance the return of results framework for epigenetic science.

Epigenetics is a fast-growing field of research that is shedding light on the ways in which interactions with the environment lead to changes in gene expression [ 1 ]. Processes such as aging and personal exposure to stress and trauma have also been associated with altered epigenetic programs [ 7 ]. As human epigenome mapping and epigenetic research continue to progress, with the potential to influence our understanding of environmental exposures, community health, and the health of future generations [ 8 , 9 , 10 ], determining which individual epigenetic research results might be communicated to research participants and how this communication should take place are of growing importance.

The return of research results and incidental findings is a topic that has been explored at great length, mostly in the fields of genetics and imaging [ 11 , 12 , 13 , 14 ]. Although epigenetic research is still in its infancy, it is expected to elucidate many aspects of human health.

Scientific and bioethics considerations already point to a number of areas where the potential risks and challenges of the return of research results might differ in type or scale from those relating to genetic data [ 15 , 16 , 17 , 18 , 19 ], and researchers have called for further guidance on the subject [ 17 , 19 ]. These differences are likely to impact notions of the clinical validity and actionability of epigenetic results, privacy considerations, and assessment of the circumstances that warrant the sharing of results, both with the research participants themselves and with other individuals who may be concerned for example, those who have had similar environmental exposures.

The IHEC Bioethics Workgroup, an interdisciplinary group of researchers in science, ethics, policy, and the law, therefore formed a Subgroup to anticipate and consider the ethical, legal, and social issues ELSI raised by the return of epigenetic research results. This is not meant to imply that further results should not be returned under certain circumstances, but clinically valid and actionable individual results, whether they are incidental findings or directly related to the research study, represent a minimum threshold for the type of results to be considered.

Therefore, we identified a number of characteristics and considerations concerning epigenetic data that could help researchers to determine which results should be returned according to the two criteria of clinical validity and actionability. Other, more procedural recommendations were derived and adapted from guidelines and literature on the return of genetic results. These included the well-established requirement that results be returned only when the participant has accepted to receive the results after having been given the option of agreeing or declining to this through an informed consent process [ 22 , 24 ].

We also warn of the possibility that epigenetic information may not be protected under genetic non-discrimination laws because these laws use language that is specific to genetics and may not cover all epigenetic data. Given the uncertainty about whether genetic non-discrimination laws apply to epigenetic data, some individuals may be reluctant to enroll in specific epigenetic studies or to give broad consent to the use of their biospecimens in research that could result in analysis of their epigenetic information.

Thus, genetic non-discrimination laws may need to be applied in a way that includes epigenetic data, or new laws focusing specifically on epigenetics may need to be enacted. Finally, ethical issues related to the disclosure of incidental findings or the return of results will depend on the age and cognitive capacity of the research participant, including the potential for prenatal epigenetic testing.

For example, it may be preferable to offer certain results, such as the risk of adult-onset conditions, to children once they are able to consent to this themselves [ 32 ].

Furthermore, it may not be appropriate for parents or legally authorized representatives to refuse to receive actionable results on behalf of children or incapable adults [ 33 ]. This need is well-established in guidelines for the return of genetic results [ 14 , 34 , 35 ]. Definitive molecular diagnosis of imprinting disorders, such as Beckwith—Wiedemann syndrome which is mainly caused by genetic or epigenetic defects in the chromosome 11p Even for this very rare group of diseases, however, an underlying DNA sequence change mutation is commonly required to return a clinical diagnosis.

Given the current uncertainty regarding the clinical significance and application of the vast majority of epigenetic data, returning clinically valid, actionable results from epigenetic research studies would require a careful process of scientific and clinical review, both across the field and of individual study results.

As more systematic evidence of the epigenetic causes of disease is only beginning to emerge from large-scale epigenome projects [ 21 , 37 , 38 , 39 , 40 , 41 ], the establishment of exhaustive criteria for assessing the clinical validity and actionability of epigenetic data would be premature at this time.

Therefore, we focused on framing in general terms how epigenetic evidence might eventually compare to genetic data, drawing on the criteria and scoring systems that have evolved over many years to assess the significance and clinical interpretation of genetic variants [ 42 , 43 , 44 , 45 , 46 ]. This entailed breaking down the assessment of epigenetic data that could potentially be communicated to participants into the following constituent areas:.

The accuracy of the epigenetic data with respect to both the technology used and the source material cell composition, sample purity. The stability of the epigenetic data. Some epigenetic marks are more dynamic than others, so multiple measurements over time might be required to determine their significance [ 47 , 48 ]. The existing level of evidence that a variant or mark may cause disease or is associated with disease, the magnitude of such disease risk, and the nature of the disease.

And finally, the possibility of treating or preventing disease or epigenetic risk variants for example, by systemic or targeted epigenetic therapy, or through epigenetic screening. In addition, we proposed specific terminology to conceptualize the typical levels of evidence that are found in discussions of epigenetic risk and disease. Disease-associated or disease-causing variants would thus fall into one of the following groups:.

Associated variants: variants supported by statistics only for example, in an epigenome-wide association study EWAS. Inferred variants: variants supported by statistics and inferred functional evidence for example, involvement in a plausible mechanism that has been inferred from additional data. Causal variants: variants supported by statistics and for which disease-causality has been demonstrated for example, in conjunction with genetic variants or where genetic variants have been ruled out.

Causal variants are candidates for clinical validation as a first step towards actionability. They may also be found to confer protection against disease. We hope that these categories will serve as a starting point for defining levels of evidence in different areas of epigenetics, as has been done in evaluating the clinical validity of gene—disease associations, for example, by the Clinical Genome Resource ClinGen [ 46 , 49 ].

ClinGen is an initiative to provide an authoritative central resource that defines the clinical relevance of genes and genetic variants for use in precision medicine and research. Approaches that are commonly used to demonstrate the causality of epigenetic variants are genetic manipulation of the DNA sequence underlying an epigenetic variant or of the enzymes that are responsible for the establishment or removal of the epigenetic variant, or targeted editing of the epigenetic variant itself [ 50 ].

Although we acknowledge that epigenetic variants and their clinical interpretation may differ considerably from genetic variants, we aimed to achieve two goals with this preliminary framework. First, to place the epigenetic research result that a researcher may be considering communicating in the context of a thorough assessment of its analytical, scientific and clinical validity. Second, to frame the result in terms of its likely impact on participants, both in its relevance to participant health and its broader significance.

For example, epigenetic data might indicate an environmental or community exposure, resulting in epigenetic risk variants that could be avoided, such as acceleration of the accumulation of altered DNA methylation biomarkers of aging the epigenetic clock [ 53 ].

Actionability could therefore include clinical actions to prevent or treat disease or epigenetic risk variants, as well as non-clinical actions that could be enabled by knowledge of the epigenetic data, such as health-related life choices, including reproductive decisions for example, changing diet or other behaviors that might be involved in health-related epigenetic variation.

The scope of the data that may potentially be of interest to participants is wide, and we certainly did not intend to suggest returning all results in all circumstances. Epigenetic reversibility may also strengthen the ethical argument in favor of disclosing an epigenetic research result, as it may allow for greater preventive or treatment opportunities.

While their inference is not yet unequivocal, at least quantitatively, especially for the more intangible exposures such as exposure to stress, it is possible that such individual research results could be of interest to research participants.

Research in this area, and into other environmental exposures, is growing [ 59 , 60 ]. As exposure science has moved from measuring chemicals in the environment to biomonitoring of such exposures in the population, novel models of community-driven return of results and broader communication plans are emerging [ 62 ].

Individual epigenetic information may be of interest to participants who simply wish to know about their own health status or to influence community health decisions. However, such information also has potential implications that extend to the area of public policy, and more specifically, to areas of environmental tort where injury occurs via toxic exposure and reproductive tort where injury occurs either pre-conception or in utero [ 63 , 64 ].

For example, evidence is emerging that toxicity from exposure to certain chemical hazards is driven at least in part by epigenetic mechanisms, and researchers have expressed concerns that assisted reproductive technologies may cause epigenetic damage to embryos [ 28 , 64 , 65 ]. Both environmental and reproductive torts are founded on responsibility for harmful exposure and involve proof of three elements: breach of duty, causation, and injury [ 64 , 66 , 67 ].

Of these, the causal element presents a particular conundrum in environmental and reproductive tort because the scientific evidence is not always sufficiently clear to establish a direct causal link between the action entailed in the breach of duty and the harm suffered by the plaintiff [ 66 , 68 ].

Although evidence of general causation is often provided by epidemiological data, evidence of specific causation requires a more fine-grained understanding most of the time not available of the biological mechanisms underlying such statistical associations between exposure and harm.

By providing insights at the molecular level into how significant health risks may be acquired through different manners of exposure, epigenetic research could fill the existing gap in establishing actionable evidence of specific causality [ 67 , 69 ]. Finally, a few studies of transgenerational epigenetic effects, mainly in mouse models, indicate that environmental and behavioral epigenetic signatures could be inherited [ 8 , 9 , 10 , 52 , 70 , 71 , 72 , 73 ].

This possibility, if confirmed, might add to the range of research data that could potentially be of interest to individuals, but it may also raise particular privacy concerns because the data would not only expose the environmental and behavioral information of the research participant, but also possibly that of their parents and grandparents.

Disclosing personal genetic information to biological relatives can sometimes benefit family members who share similar genetic-risk profiles. In the United States, federal health privacy regulations prohibit the nonconsensual disclosure of health information except in circumstances inapplicable here, such as disclosures to public health or law enforcement officials [ 78 ]. The superior approach is for health care providers to counsel, encourage, and support patients to disclose relevant genetic information to their at-risk relatives [ 79 ].

This approach will also benefit researchers who investigate DNA sequence mutations and other changes that are induced by environmental exposures [ 82 ]. Consider the following hypothetical scenario: numerous studies have shown that a pesticide causes specific epigenetic changes and phenotypes at the population level.

An investigator finds out that one of the research participants in their study, who has worked as a farmer all their life, has these epigenetic marks of exposure to the pesticide.

Therefore, the exposure occurred in all likelihood at the workplace. The Personal Genome Project UK PGP-UK [ 83 ] conducted a small pilot trial in to gain experience and a first insight into any issues associated with reporting incidental epigenetic findings to study participants.

Using open consent and open access data sharing protocols [ 84 ], PGP-UK recruited ten volunteers who agreed to receive incidental epigenetic findings from the analysis of their DNA methylomes in addition to their standard genome reports. Three categories of findings were reported sex, age, and smoking , for which the analysis was judged to be sufficiently mature based on independent validation and replication.

The methylome reports [ 85 ] were based on the analysis of around , genome-wide CpG sites in two specimens blood and saliva from each participant [ 86 ]. In this small initial trial, there was high participant interest in, and acceptance of, receiving incidental epigenetic findings, as assessed through discussion groups and follow-up with volunteers, particularly the results associated with environmental exposures [ 86 ].

This supports our view that results other than clinically actionable results are potentially of great interest to research participants. It also provides limited evidence that participants could also be comfortable with receiving results of uncertain clinical significance, although the level of support provided for the return of results communication process in this trial may not be as feasible for studies involving much larger groups of research participants.

Although we expect good communication practices to improve participant understanding of individual results and encourage such efforts, we would not assume that personal preferences regarding the receipt of results would necessarily differ in the absence of such support.

Indeed, social science studies have shown that the vast majority of participants in genetics research and biobanking initiatives wish to receive individual results [ 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ]. Furthermore, a large multi-study survey found that providing a choice of different consent and data sharing models did not have a significant impact on willingness to participate in a biobank [ 96 ].

With these P-t-C, we aimed to draw attention to the ELSI associated with the return of epigenetic research results and we have outlined both the norms that have emerged for genetic research results that are relevant and new issues to consider for epigenetic research.

Much remains to be determined before we can arrive at detailed guidance for the return of specific epigenetic results, such as the recommendations that have been produced for clinical genome sequencing in the USA [ 97 , 98 ]. This will involve considerable research efforts to better understand fundamental epigenetic and epigenomic processes and their relationship to disease, as well as studies of the clinical validity and actionability of epigenetic data.

We believe, however, that discussions about the strength of epigenetic findings and their implications for health and disease must begin now, while our understanding of the role of epigenetics is growing. Although we found it useful to build on ELSI guidance from the field of genetics, epigenetic data raise important new challenges that may eventually lead to a very different framework for the return of results. We focused here on the return of individual research results to participants, but the issues of the broader communication and public understanding of epigenetics should not be left out of the discussion.

With these P-t-C, we hope to stimulate innovative, interdisciplinary public conversations about epigenetics and the implications of this science for individuals, families, and societies. Decoding the DNA methylome of mantle cell lymphoma in the light of the entire B cell lineage. Cancer Cell. Great expectations—epigenetics and the meandering path from bench to bedside.

Biom J. Google Scholar. Epigenetics in cancer: a hematological perspective. PLoS Genet. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Allis CD, Jenuwein T. The molecular hallmarks of epigenetic control.

Nat Rev Genet. Aging, exceptional longevity and comparisons of the Hannum and Horvath epigenetic clocks.

The epigenetics of diabetes, obesity, overweight and cardiovascular disease

Many cofactors that are produced during metabolic reactions e. Circadian rhythms and aging represent examples of processes that are influenced by these types of interactions. Epigenetic changes e. Drugs that reverse such changes are emerging as effective cancer therapies. Epigenetic mechanisms play important roles in neurogenesis. For example, DNA methylation regulates the differential expression of Protocadherins, cell-surface receptors required for neuronal identity. Epigenetic marks must be transmitted during cell division.

Citation: Harem Othman Smail. The epigenetics of diabetes, obesity, overweight and cardiovascular disease[J]. AIMS Genetics, , 6 3 : Article views PDF downloads Cited by 0. Harem Othman Smail.

Invasive species represent a serious ecological threat for many ecosystems worldwide and provide a unique opportunity to investigate rapid adaptation and evolution. Genetic variation allows populations of organisms to be both robust and adaptable to different environmental conditions over evolutionary timeframes. In contrast, invasive animals can rapidly adapt to new environments, with minimal genetic diversity. Thus, the extent to which environmental effects can trigger epigenetic responses is particularly interesting for understanding the role of epigenetics in rapid adaptation. In this review, we provide a brief overview of the different epigenetic mechanisms that control gene expression, and emphasize the importance of epigenetics for environmental adaptation. We also discuss recent publications that provide important examples for the role of epigenetic mechanisms in environmental adaptation.


Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Epigenetics is the study of variations in gene function phenotypes that are somatically heritable and sometimes also from one generation to the next , but which are not caused by genetic alterations.

Richard A. The American Biology Teacher 1 April ; 74 4 : — Epigenetics is emerging as one of the most dynamic and vibrant biomedical areas.


In biology , epigenetics is the study of heritable phenotype changes that do not involve alterations in the DNA sequence. Such effects on cellular and physiological phenotypic traits may result from external or environmental factors, or be part of normal development. The standard definition of epigenetics requires these alterations to be heritable [3] [4] in the progeny of either cells or organisms. The term also refers to the changes themselves: functionally relevant changes to the genome that do not involve a change in the nucleotide sequence. Examples of mechanisms that produce such changes are DNA methylation and histone modification , each of which alters how genes are expressed without altering the underlying DNA sequence. Gene expression can be controlled through the action of repressor proteins that attach to silencer regions of the DNA.

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Я ему не поверил. - Но зачем он вам об этом сообщил? - спросила Сьюзан.  - Хотел предложить вам купить этот алгоритм. - Нет. Это был шантаж. Все встало на свои места.


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To date, much of the focus in. 'environmental epigenetics' has been on DNA methyla- emerging patterns and implications. Robert Feil1 and Mario F. ALL LINKS ARE ACTIVE IN THE ONLINE PDF. REVIEWS. NATURE.

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