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靶向测序方法:自杀受害者血液和脑区DNA甲基化与基因表达的综合分析

Targeted sequencing approach: Comprehensive analysis of DNA methylation and gene expression across blood and brain regions in suicide victims.

作者信息

Kouter Katarina, Zupanc Tomaž, Videtič Paska Alja

机构信息

Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.

Institute of Forensic Medicine, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.

出版信息

World J Biol Psychiatry. 2023 Jan;24(1):12-23. doi: 10.1080/15622975.2022.2046291. Epub 2022 Mar 9.

Abstract

OBJECTIVES

Epigenetic mechanisms are involved in regulation of many pathologies, including suicidal behaviour. However, the factors through which epigenetics affect suicidal behaviour are not fully understood.

METHODS

We analysed DNA methylation of eight neuropsychiatric genes (1, , , 2, , , , and ) in brain regions (hippocampus, insula, amygdala, Brodmann area 46) and blood of 25 male suicide victims and 28 male control subjects, using bisulphite next-generation sequencing.

RESULTS

Comparing mean methylation values, notable changes were observed in (insula -value = 0.05), (insula -value < 0.001, blood -value = 0.001), (insula -value = 0.03, blood -value = 0.016), (blood -value < 0.001), (insula -value = 0.05, blood -value = 0.024) and (hippocampus -value = 0.001, insula -value = 0.002, amygdala -value = 0.014). Comparing methylation pattern between blood and brain, similarity was observed between blood and insula for Gene expression analysis in hippocampus revealed changes in expression of (-value = 0.049), (-value = 0.017) and (-value = 0.053).

CONCLUSIONS

Results provide an insight into the altered state of DNA methylation in suicidal behaviour. Epigenetic differences could therefore affect suicidal behaviour in both previously known and in novel neuropsychiatric candidate genes.

摘要

目的

表观遗传机制参与调控包括自杀行为在内的多种病理过程。然而,表观遗传学影响自杀行为的因素尚未完全明确。

方法

我们采用亚硫酸氢盐新一代测序技术,分析了25例男性自杀受害者及28例男性对照者大脑区域(海马体、脑岛、杏仁核、布罗德曼46区)和血液中8个神经精神基因(1、 、 、2、 、 、 、 )的DNA甲基化情况。

结果

比较平均甲基化值,在 (脑岛 -值 = 0.05)、 (脑岛 -值 < 0.001,血液 -值 = 0.001)、 (脑岛 -值 = 0.03,血液 -值 = 0.016)、 (血液 -值 < 0.001)、 (脑岛 -值 = 0.05,血液 -值 = 0.024)和 (海马体 -值 = 0.001,脑岛 -值 = 0.002,杏仁核 -值 = 0.014)中观察到显著变化。比较血液和大脑之间的甲基化模式,发现 基因在血液和脑岛之间具有相似性。海马体中的基因表达分析显示 ( -值 = 0.049)、 ( -值 = 0.017)和 ( -值 = 0.053)的表达发生了变化。

结论

研究结果为自杀行为中DNA甲基化的改变状态提供了见解。因此,表观遗传差异可能会影响已知的以及新的神经精神候选基因中的自杀行为。

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