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Figure 1. Interaction of endogenous (genetic and developmental) and exogenous (environmental) factors in generating changes in the epigenome during an individual's lifespan. Environmental factors include chemicals, toxins, physical agents and behavioral, dietary, social and other lifestyle factors. These exert effects preferentially at different times during development. Genetic variation affects developmental processes, responses to environmental factors and the molecular mechanisms that mediate epigenetic change. The arrows indicate that these three forces continue to interact throughout life to modify the epigenome. Maximum epigenetic change occurs when genotype, developmental stage and environmental exposure operate additively (exposure at sensitive stage in individual genetically predisposed to effect).
(Figure omitted. See article PDF.)
Figure 2. Relationship between epigenetic state, disease threshold and environment. Individual A represents a reference pattern, wherein the epigenome changes at a given rate throughout life and reaches a threshold to elicit a disease or disorder. Individual B experienced an acute early-life exposure that resulted in a parallel path of change, but reaching the threshold earlier than individual A. Individual C experienced a change in environment that increased the rate of change. Individual D began life at a different epigenetic state (this could be higher or lower) and then progressed in parallel with individual A. Individual E experienced a change in environment that lessened the pace of acquiring epigenetic change, such as an improvement in environment. Individual F experienced an acute drop in epigenetic change, perhaps as a result of a sudden improvement of environment, and then progressed in parallel with individual A.
(Figure omitted. See article PDF.)
The Human Genome Project promises many new and exciting ways to use human genetic data to understand, prevent, treat and cure human diseases and disorders. Coupled with emerging stem cell technologies, we face tantalizing prospects and unparalleled opportunities for improving health, lifestyle, wellbeing and lifespan, even at the level of individualized approaches. This exciting genome-science revolution is occurring as a backdrop to an alarming increase in the prevalence of a range of human disorders and diseases. Obesity, diabetes, asthma, autism spectrum disorders (ASDs) and attention deficit hyperactivity disorder (ADHD) are all increasing at dramatic rates (Table 1).
Obesity affects over 33% of Americans. Although obesity is not a disease phenotype, in and of itself, it contributes to the development...