与人类个人失调和异常行为相关基因的 DNA 甲基化差异。

IF 3.1 Q2 NEUROSCIENCES AIMS Neuroscience Pub Date : 2024-03-25 eCollection Date: 2024-01-01 DOI:10.3934/Neuroscience.2024003
I B Mosse, N G Sedlyar, K A Mosse, A V Kilchevsky
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引用次数: 0

摘要

基因表达的表观遗传调控与精神障碍的发展有关,包括异常行为、大脑发育和人格障碍。人们已经研究了大量基因与压力和抑郁之间的活性关联,但其中大多数基因的研究结果却相互矛盾。我们的研究旨在探讨甲基化水平的变化对人格障碍和偏差行为的发展可能产生的影响。我们对从外周血细胞中提取的 DNA 样本中 21 个目标区域(包括 12 个基因的启动子和内含子区域)的 CpG 岛进行了系统研究,以了解其甲基化状况。对转换后的 DNA 样品进行了高通量测序,并在 Bismark 管道中对 CpG 岛 "原始顶链 "上的甲基化位点进行了调用。77 份患者样本和 48 份对照样本的初始甲基化图谱显示,6 个基因中的 7 个 CpG 位点存在显著差异。HTR2A(p-value = 1.2 × 10-13)和 OXTR(p-value = 2.3 × 10-7)基因的靶位点甲基化程度最高。这些数据支持了之前的报告,即 DNA 甲基化的改变可能在与人格障碍和异常行为相关的基因表达失调中扮演重要角色,并证实了其作为生物标记物的潜在用途,可用于改善诊断、预后和治疗反应评估。
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DNA methylation differences in genes associated with human personal disorders and deviant behavior.

Epigenetic regulation of gene expression is involved in the progression of mental disorders, including deviant behavior, brain developmental, and personality disorders. The large number of genes has been studied for their activity association with stress and depression; however, the obtained results for the majority of these genes are contradictory. The aim of our study was to investigate the possible contribution of methylation level changes to the development of personality disorders and deviant behavior. A systematic study of CpG Islands in 21 target regions, including the promoter and intron regions of the 12 genes was performed in DNA samples extracted from peripheral blood cells, to obtain an overview of their methylation status. High-throughput sequencing of converted DNA samples was performed and calling of the methylation sites on the "original top strand" in CpG islands was carried out in the Bismark pipeline. The initial methylation profile of 77 patients and 48 controls samples revealed a significant difference in 7 CpG sites in 6 genes. The most significant hypermethylation was found for the target sites of the HTR2A (p-value = 1.2 × 10-13) and OXTR (p-value = 2.3 × 10-7) genes. These data support the previous reports that alterations in DNA methylation may play an important role in the dysregulation of gene expression associated with personality disorders and deviant behavior, and confirm their potential use as biomarkers to improve thediagnosis, prognosis, and assessment of response to treatment.

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来源期刊
AIMS Neuroscience
AIMS Neuroscience NEUROSCIENCES-
CiteScore
4.20
自引率
0.00%
发文量
26
审稿时长
8 weeks
期刊介绍: AIMS Neuroscience is an international Open Access journal devoted to publishing peer-reviewed, high quality, original papers from all areas in the field of neuroscience. The primary focus is to provide a forum in which to expedite the speed with which theoretical neuroscience progresses toward generating testable hypotheses. In the presence of current and developing technology that offers unprecedented access to functions of the nervous system at all levels, the journal is designed to serve the role of providing the widest variety of the best theoretical views leading to suggested studies. Single blind peer review is provided for all articles and commentaries.
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