DNP 810 Topic 3 Discussion Question Two
DNP 810 Topic 3 Discussion Question Two
Why is it important to have a comprehensive health and physical assessment that includes information on environment and genomic influences? How can the doctoral-prepared nurse apply this information in practice? Explain. Support your rationale with a minimum of two scholarly sources.
The etiologic paradigm of complex human disorders such as autism is that genetic and environmental risk factors are independent and additive, but the interactive effects at the epigenetic interface are largely ignored. Genomic technologies have radically changed perspective on the human genome and how the epigenetic interface may impact complex human disorders. Here, I review recent
genomic, environmental and epigenetic findings that suggest a new paradigm of “integrative genomics” in which genetic variation in genomic size may be impacted by dietary and environmental factors that influence the genomic saturation of DNA methylation. Human genomes are highly repetitive, but the interface of large-scale genomic differences with environmental factors that alter the DNA methylome such as dietary folate is under-explored.
In addition to obvious direct effects of some environmental toxins on the genome by causing chromosomal breaks, non-mutagenic toxin exposures correlate with DNA hypomethylation that can lead to rearrangements between repeats or increased retrotransposition. Since human neurodevelopment appears to be particularly sensitive to alterations in epigenetic pathways, a further focus will be on how developing neurons may be particularly impacted by even subtle alterations to DNA methylation and proposing new directions towards understanding the quixotic etiology of autism by integrative genomic approaches.
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Environmental Toxins Negatively Impact Global DNA Methylation
The epigenetic modification of DNA methylation acts at the interface of genetic and environmental factors. As part of the emerging field of “environmental epigenetics,” a variety of environmental toxins with known adverse impacts on human health or neurodevelopment have been investigated for their potential effects on DNA methylation and other epigenetic effects (reviewed in ref. 1). Arsenic, cadmium, benzene and air pollution are exposures associated with reduction of DNA methylation levels at LINE1 and/or Alu repeats in human tissues.2–6 In mouse models of human exposures, methylmercury resulted in hypermethylation of brain derived neurotropic factor (Bdnf) in hippocampus7 and diethylstilbestrol exposure reduced global methylation in the uterus.8 In a human Greenlandic Inuit population with high persistent organic pollutant (POP) levels, reduced global DNA methylation (LINE1) was observed with increased POP levels.9 Furthermore, prenatal exposure of a rat model with organochloride pesticides, methylmercury, POPs or a mixture of all three chemical classes showed that POPs in the mixture correlated with reduced DNA methylation levels in liver.10
Within the class of POPs, polychlorinated biphenyls (PCBs) are a widely distributed class of environmental pollutants previously used in industrial products until adverse health effects were recognized in the 1970s resulting in discontinued use. The developmental neurotoxicity of PCBs became devastatingly apparent after the large-scale consumption of PCB-contaminated rice oil that occurred in 1968 in Japan and in 1979 in Taiwan.11,12 PCBs are known to disrupt neurotransmitter systems, endocrine systems and intracellular signaling pathways.13,14 While PCB levels are gradually declining in the environment following the discontinued use, a related class of POPs, the polybrominated diphenyl ethers (PBDEs), are currently used as commercial flame-retardants and are a growing concern for human exposures. Our recent analyses of perinatal PBDE exposure in a genetic mouse model susceptible to social behavioral deficits showed global hypomethylation in brain associated with adverse social and cognitive behavioral outcomes (Woods et al., in preparation).
The major future challenge that will be explored in this review is understanding how DNA methylation of human repetitive elements interacts with environmental risk and protective factors in the etiology of a complex genetic disorder such as autism.
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