Genomic imprinting disorders: lessons on how genome, epigenome and environment interact

Abstract

Genomic imprinting, the monoallelic and parent-of-origin-dependent expression of a subset of genes, is required for normal development. Its disruption leads to human disease involving isolated or multi-locus epigenetic changes that can be traced back to alterations of cis-acting sequences or trans-acting factors controlling the establishment, maintenance and erasure of germline epigenetic imprints or may have no evident genetic cause. Recent insights into the dynamics of the epigenome including the effect of environmental factors suggest that the developmental outcomes and heritability of imprinting disorders are influenced by interactions between the genome, the epigenome and the environment in germ cells and early embryos. In this Review, we discuss the latest advances in the study of genomic imprinting, focusing on the imprinting life-cycle and its possible errors leading to human diseases. We discuss the modes of inheritance of imprinting defects and 2 evidences from humans and animal models that environmental factors may influence genomic imprinting. Finally, we highlight areas requiring additional research that could complete our understanding of imprinting disorders, as well as new technological advances that might correct imprinting errors.

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ORCID for Deborah Mackay: orcid.org/0000-0003-3088-4401

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