unsuspecting researcher might inadvertently and erroneously attribute the child’s impoverished social relatedness to the caregiver’s withdrawal, when in fact it was caused by a particular genetic variant.

Epigenetic Effects

Epigenetic effects are potentially heritable alterations of gene expression that do not involve actual modification of the DNA sequence. Instead, alterations in the level of gene expression are induced by changes in the three-dimensional packaging of DNA that in turn make a gene either more or less amenable to production of a protein product. All known mechanisms that produce epigenetic changes in gene expression involve enzymatic processes that add or remove substrates either from the DNA or from histone proteins that are physically associated with DNA and that determine its three-dimensional packing structure (Tsankova, Renthal, et al., 2007). Epigenetic modifications of gene expression are in continual flux, as competing factors modify and unmodify DNA and its associated proteins, as well as their related behavioral phenotypes.

Epigenetic determinants are increasingly invoked as possible explanations for a multitude of “complex genetic” phenotypes, in which multiple genes are each thought to account for a small amount of variance in the clinical phenotype. Moreover, recent research has shown that epigenetic mechanisms can produce short-term adaptation of the phenotype to a changing environment. For example, abundant naturalistic and experimental evidence in humans and animal models has shown that early experience influences reactivity to stress later in life, even into adulthood, and that epigenetic modification of genes that encode components of the stress response can contribute to these enduring effects (Kaffman and Meaney, 2007; Weaver, 2007).

Perhaps most remarkably, a changing environment has been shown to trigger epigenetic effects that can be transmitted across generations, in species as diverse as yeast and humans (Rakyan and Beck, 2006; Richards, 2006; Whitelaw and Whitelaw, 2006). The quality of maternal care given to rat pups, for example, produces epigenetic modifications of gene expression in the brains of the pups that influence the quality of maternal care they provide as adults to their own offspring. This cross-generation transmission has been shown to account for variability in maternal behavior toward offspring that is either nurturing or neglectful (Champagne, 2008).

Several examples suggest that epigenetic mechanisms are important in understanding the causes and in improving the prevention and treatment of MEB disorders (Tsankova, Renthal, et al., 2007). One well-known example is the Prader-Willi and the Angelman syndromes, disorders with highly distinct phenotypes that are nevertheless both caused by a mutation

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