Early environmental exposures can have long-term effects on child's development and health. Epigenetic modifications may partly explain these effects, and studying them could lead to significant advances in our understanding of the underlying mechanisms. This review summarises recent data on epigenetic and environmental epidemiology during the first 1000 days of life for several common exposures, including tobacco, phenols and phthalates, air pollutants, ambient temperature and vegetation.
Even today, 'epigenetics' is a rather difficult field to define. The explosive growth of epigenetics over the last twenty years is sometimes seen as a revolutionary event in the life sciences, a paradigm shift that would devalue genetics or the standard view of the evolutionary synthesis. The aim of this paper is to place this controversial issue in its historical context. Building on the excellent work of David Haig, I will show that in the late 1950s, the modern concept of epigenetics emerged as an extension of the nascent theory of molecular biology. Given that genetic information was assimilated to the DNA sequence, and that each cell of an organism was supposed to possess a complete genome, it was thought that certain as yet undiscovered molecular mechanisms were necessary to regulate gene expression. These hypothetical "epigenetic systems", which would not modify the DNA sequence, should also have heritable effect on gene expression, which would explain the stability of cell differentiation during embryogenesis.
The development of sequencing technologies and their increased accessibility in clinical services and genetic laboratories have considerably accelerated the identification of genetic variants associated with rare diseases (RDs). Among these, Mendelian disorders of the epigenetic machinery (MDEM) are rare monogenic diseases characterized by the presence of mutations in genes encoding epigenetic regulators that play a key role in organismal development and cellular functions. Loss of function of these regulators is expected to lead to epigenetic modifications that profoundly affect genome expression and cellular identity. Disruptions in DNA methylation profiles have been documented in MDEMs, emerging as a useful diagnostic tool. The current challenge is to determine whether and how these epigenomic alterations drive the mechanisms underlying the clinical manifestations in patients suffering from this class of diseases. Studying MDEMs may therefore shed light on the important role of epigenetic information in health and disease, particularly the mechanisms involved in the development and understanding of complex pathologies, such as neurodevelopmental disorders and cancer.
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