A genomic point-of-view on environmental factors influencing the human brain methylome

Environmental Toxins Negatively Impact Global DNA Methylation

2011 Study Abstracts

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.

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 . In mouse models of human exposures, methylmercury resulted in hypermethylation of brain derived neurotropic factor (Bdnf) in hippocampus and diethylstilbestrol exposure reduced global methylation in the uterus.

  • Read and download the full study (free access) A genomic point-of-view on environmental factors influencing the human brain methylome, on the NCBI, PubMed, PMC3154427, 2011 Jul.
  • Image of a Representation of a DNA molecule that is methylated, by Christoph Bock, Max Planck Institute for Informatics – Own work, CC BY-SA 3.0 Wiki.

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