Epigenetic inheritance and the missing heritability.
Epigenetic inheritance and the missing heritability.
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DOI：
10.1186/s40246-015-0041-3
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发表时间：
2015-07-28
期刊：
影响因子：
4.5
通讯作者：
Alberti S
中科院分区：
文献类型：
--
作者：
Trerotola M;Relli V;Simeone P;Alberti S
复杂生理性状和疾病的全基因组关联研究一致发现，相关的遗传因素，如等位基因多态性或DNA突变，只能解释预期的遗传分数的一小部分。这种差异被称为“缺失遗传性”，其潜在因素和分子机制尚未建立。表观遗传程序可能占“缺失遗传力”的很大一部分。表观遗传修饰，如DNA甲基化和染色质组装状态，反映了基因组的高可塑性，并有助于稳定地改变基因表达，而不改变基因组DNA序列。复杂性状的一致组成部分，如与人类身材/身高，生育力和食物代谢或遗传缺陷有关的那些，已被证明对环境或营养条件有反应，并被表观遗传遗传。从发育过程中的表观遗传基因组重编程、干细胞分化/去分化和模式生物中获得的知识，今天正在阐明（a）细胞间表观遗传性状的有丝分裂遗传，（B）代间减数分裂表观遗传遗传，和（c）真正的跨代遗传的机制。这些机制已被证明包括DNA甲基化的不完全消除、亲本效应、不同RNA类型（mRNA、非编码RNA、miRNA、siRNA、皮尔纳）的传递以及组蛋白标记子集的持续存在。
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.