title: Epigenetic inheritance and the missing heritability.
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.
authors.affiliation: Unit of Cancer Pathology, CeSI, Foundation University 'G. d'Annunzio', Chieti, Italy. marco.trerotola@gmail.com.
authors.forename: Marco
authors.initials: M
authors.lastname: Trerotola
authors.affiliation: Unit of Cancer Pathology, CeSI, Foundation University 'G. d'Annunzio', Chieti, Italy. valeria.relli@gmail.com.
authors.forename: Valeria
authors.initials: V
authors.lastname: Relli
authors.affiliation: Unit of Cancer Pathology, CeSI, Foundation University 'G. d'Annunzio', Chieti, Italy. simeone.pasquale@gmail.com.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Simeone
authors.affiliation: Unit of Cancer Pathology, CeSI, Foundation University 'G. d'Annunzio', Chieti, Italy. s.alberti@unich.it.|Department of Neuroscience, Imaging and Clinical Sciences, Unit of Physiology and Physiopathology, 'G. d'Annunzio' University, Chieti, Italy. s.alberti@unich.it.
authors.forename: Saverio
authors.initials: S
authors.lastname: Alberti
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D065150:Cellular Reprogramming / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D008540:Meiosis / Q000235:genetics; D008938:Mitosis / Q000235:genetics