Environmental epigenomics and disease susceptibility

Abstract

Human epidemiological studies and animal investigations provide compelling evidence that prenatal and early postnatal environmental factors influence the adult risk of developing various chronic diseases, such as cancer, cardiovascular disease, diabetes, obesity and behavioural disorders such as schizophrenia. The developmental origins of adult-onset disease hypothesis proposes that the evolution of developmental plasticity, which enables an organism to adapt to environmental signals during early life, can also increase the risk of developing chronic diseases when there is a mismatch between the perceived environment and that which is encountered in adulthood. Epigenetics is the study of alterations in gene expression that occur not by changing the DNA sequence, but by modifying DNA methylation and remodelling chromatin structure. Prenatal and postnatal environmental exposures could be linked to phenotypic changes later in life through the alteration of the epigenetic marks that regulate the functional output of the information that is stored in the genome. In support of this postulate, maternal methyl-donor supplementation during pregnancy with folic acid, vitamin B₁₂, choline and betaine was shown to effect the phenotype of the A^vy (viable yellow agouti) offspring by directly altering the epigenome. Studies with the fungicide vinclozolin demonstrate that heritable environmentally induced epigenetic modifications can also underlie transgenerational alterations in phenotype. Novel genome-wide experimental and bioinformatic techniques are now being used to identify epigenetically labile genes in humans. Such approaches will hopefully allow for the development of unique epigenetic-based diagnostic, prevention and therapeutic strategies for human diseases.