Mechanisms of Epigenetic Variation: Polymorphic Imprinting

Phenotypic variation among individuals often results from complex interactions between multiple factors: genetic, epigenetic, environmental and stochastic. Interaction between alleles of the same gene that is subject to allelic exclusion represents a particular case of regulatory variation. In mammals allelic exclusion is achieved through epigenetic silencing. DNA methylation, X-chromosome inactivation and genomic imprinting are the three epigenetic phenomena that are extensively studied in mammals. Genomic imprinting is differential epigenetic DNA modification of the parental alleles. This implies that genes or chromosomal regions are marked differently when they go through female or male gametogenesis. The epigenetic marks (also termed imprints or gametic marks) persist throughout life and, hence, must be faithfully transmitted and maintained through multiple mitotic divisions. However, emerging evidence suggests that genomic imprinting may vary among individuals (a phenomenon termed polymorphic imprinting), thereby providing an additional source of phenotypic variation in the population. An analysis of the reported instances of polymorphic imprinting provides clues for the understanding of mechanisms underlying interindividual imprinting variation in mammals.