Abstract
Genome-wide association studies of complex physiological traits and diseases consistently found that associated genetic factors, such as allelic polymorphisms or DNA mutations, only explained a minority of the expected heritable fraction. This discrepancy is known as “missing heritability”, and its underlying factors and molecular mechanisms are not established. Epigenetic programs may account for a significant fraction of the “missing heritability.” Epigenetic modifications, such as DNA methylation and chromatin assembly states, reflect the high plasticity of the genome and contribute to stably alter gene expression without modifying genomic DNA sequences. Consistent components of complex traits, such as those linked to human stature/height, fertility, and food metabolism or to hereditary defects, have been shown to respond to environmental or nutritional condition and to be epigenetically inherited. The knowledge acquired from epigenetic genome reprogramming during development, stem cell differentiation/de-differentiation, and model organisms is today shedding light on the mechanisms of (a) mitotic inheritance of epigenetic traits from cell to cell, (b) meiotic epigenetic inheritance from generation to generation, and (c) true transgenerational inheritance. Such mechanisms have been shown to include incomplete erasure of DNA methylation, parental effects, transmission of distinct RNA types (mRNA, non-coding RNA, miRNA, siRNA, piRNA), and persistence of subsets of histone marks.
Highlights
Patterns of heritable traits within the human population determine body phenotypes, through a deeply intertwined interaction between genetic components and the environment
Evidence is accumulating that provides insight in the mechanisms that underlie epigenetic transmission. These include the following: (1) DNA methylation, (2) histone modifications and chromatin remodeling, (3) inheritance of specific mRNAs, long non-coding RNAs and siRNAs/miRNAs, (4) feedback loops through which mRNA or protein products of a gene can stimulate its own transcription and enable “heritable states” of gene expression, and (5) the activity of chaperones such as Hsp90 that plays an important role in chromatin remodeling and can mediate epigenetic transgenerational variation
Histone post-translational modifications (PTMs) and corresponding DNA methylation patterns can affect imprinting in mammalian cells [90, 91] through the selective recruitment of effector proteins, known as “readers”, which drive chromatin packaging around nucleosomes [88, 91] (Fig. 2)
Summary
Patterns of heritable traits within the human population determine body phenotypes, through a deeply intertwined interaction between genetic components and the environment. Epigenetic heritability Epigenetic modifications, such as DNA methylation, can contribute to alter gene expression in heritable manner without affecting the underlying genomic sequences.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
