Cerrato Flavia, Sparago Angela, Ariani Francesca, Brugnoletti Fulvia, Calzari Luciano, Coppedè Fabio, De Luca Alessandro, Gervasini Cristina, Giardina Emiliano, Gurrieri Fiorella, Lo Nigro Cristiana, Merla Giuseppe, Miozzo Monica, Russo Silvia, Sangiorgi Eugenio, Sirchia Silvia M, Squeo Gabriella Maria, Tabano Silvia, Tabolacci Elisabetta, Torrente Isabella, Genuardi Maurizio, Neri Giovanni, Riccio Andrea
Dipartimento di Scienze e Tecnologie Ambientali Biologiche e Farmaceutiche, Università degli Studi della Campania "Luigi Vanvitelli", 81100 Caserta, Italy.
Genetica Medica, Università di Siena, 53100 Siena, Italy.
Genes (Basel). 2020 Mar 26;11(4):355. doi: 10.3390/genes11040355.
DNA methylation in the human genome is largely programmed and shaped by transcription factor binding and interaction between DNA methyltransferases and histone marks during gamete and embryo development. Normal methylation profiles can be modified at single or multiple loci, more frequently as consequences of genetic variants acting in cis or in trans, or in some cases stochastically or through interaction with environmental factors. For many developmental disorders, specific methylation patterns or signatures can be detected in blood DNA. The recent use of high-throughput assays investigating the whole genome has largely increased the number of diseases for which DNA methylation analysis provides information for their diagnosis. Here, we review the methylation abnormalities that have been associated with mono/oligogenic diseases, their relationship with genotype and phenotype and relevance for diagnosis, as well as the limitations in their use and interpretation of results.
人类基因组中的DNA甲基化在很大程度上是由转录因子结合以及配子和胚胎发育过程中DNA甲基转移酶与组蛋白标记之间的相互作用所编程和塑造的。正常的甲基化图谱可在单个或多个位点发生改变，更常见的是顺式或反式作用的遗传变异导致的结果，或者在某些情况下是随机发生的，或是通过与环境因素相互作用而改变。对于许多发育障碍，可在血液DNA中检测到特定的甲基化模式或特征。近期使用的研究全基因组的高通量检测方法极大地增加了DNA甲基化分析可为其诊断提供信息的疾病数量。在此，我们综述了与单基因/寡基因疾病相关的甲基化异常、它们与基因型和表型的关系及其诊断相关性，以及在其应用和结果解读方面的局限性。
