ABSTRACT
The developmental origins of health and disease (DOHaD) hypothesis postulates that early-life environmental and/or nutritional exposures can inuence developmental plasticity resulting in altered susceptibility to chronic disease development in adulthood (Barker 1997, 2004; Bateson et al. 2004). The mechanistic link between what individuals are exposed to in early life and disease formation throughout the life course appears to involve alterations to epigenetic modications, such as chromatin folding and attachment to the nuclear matrix, packaging of DNA around nucleosomes, covalent modications of histone tails, DNA methylation, and noncoding RNA. Epigenetics is the study of mitotically heritable yet potentially reversible, molecular modications to DNA, and chromatin without alteration to the underlying DNA sequence (Reik et al. 2001; Li 2002). Aberrant epigenetic gene regulation has been proposed as a mechanism of action for nongenotoxic carcinogenesis (Silva Lima and Van der Laan 2000), imprinting disorders (Murphy and Jirtle 2003), and complex disorders including Alzheimer disease (Bassett et al. 2006), schizophrenia (Petronis 2004), asthma (Vercelli 2004), and autism (Lopez-Rangel and Lewis 2006). Although DNA sequence is fairly permanent, epigenetic modications are dynamic throughout the life course and can be heavily inuenced by external factors such as the environment and nutrition (Reik et al. 2001). Thus, external effects on the epigenome may alter gene expression, potentially giving rise to phenotypic disparity including disease formation.
