Epigenetic deregulation of genomic imprinting in human disorders and following assisted reproduction.
Epigenetic deregulation of genomic imprinting in human disorders and following assisted reproduction.
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DOI：
10.1002/bdrc.20039
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发表时间：
2005-06-01
期刊：
影响因子：
--
通讯作者：
Feil, Robert
中科院分区：
文献类型：
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作者：
Arnaud, Philippe;Feil, Robert
印记基因在生长和发育的调节中发挥着重要作用，其中一些已被证明可以影响行为。它们的等位基因特异性表达取决于来自母亲或父亲的遗传，并受到“印记控制区”（ICR）的调节。 ICR 受 DNA 甲基化控制，DNA 甲基化仅存在于两个亲本等位基因之一上。在原始生殖细胞中先前存在的 DNA 甲基化被消除后，这些等位基因甲基化标记在雌性或雄性生殖系中建立。受精后，ICR 处的等位基因 DNA 甲基化在发育胚胎的所有体细胞中得以维持。这种印记的表观遗传“生命周期”（种系擦除、种系建立和体细胞维持）可能会在多种人类疾病中被破坏，包括贝克威斯-维德曼综合征（BWS）、普瑞德-威利综合征（PWS）、安格曼综合征和葡萄胎。在神经发育雷特综合征中，ICR 介导印记表达的方式受到干扰。最近的研究表明，辅助生殖技术（ART）有时也会影响印记的表观遗传周期，从而引起印记疾病综合征。这一发现需要仔细监测当前使用的和新颖的生殖技术的表观遗传效应和绝对风险。
Imprinted genes play important roles in the regulation of growth and development, and several have been shown to influence behavior. Their allele-specific expression depends on inheritance from either the mother or the father, and is regulated by "imprinting control regions" (ICRs). ICRs are controlled by DNA methylation, which is present on one of the two parental alleles only. These allelic methylation marks are established in either the female or the male germline, following the erasure of preexisting DNA methylation in the primordial germ cells. After fertilization, the allelic DNA methylation at ICRs is maintained in all somatic cells of the developing embryo. This epigenetic "life cycle" of imprinting (germline erasure, germline establishment, and somatic maintenance) can be disrupted in several human diseases, including Beckwith-Wiedemann syndrome (BWS), Prader-Willi syndrome (PWS), Angelman syndrome and Hydatidiform mole. In the neurodevelopmental Rett syndrome, the way the ICR mediates imprinted expression is perturbed. Recent studies indicate that assisted reproduction technologies (ART) can sometimes affect the epigenetic cycle of imprinting as well, and that this gives rise to imprinting disease syndromes. This finding warrants careful monitoring of the epigenetic effects, and absolute risks, of currently used and novel reproduction technologies.