基因编辑是常见炎症疾病的基因风险
Qin Li1, Michael J Gloudemans2,3, Jonathan M Geisinger1
1Department of Genetics, Stanford University, Stanford, CA, USA.
Nature
|August 3, 2022
概括
通过ADAR编辑RNA可以抑制免疫反应和炎症. 与炎症性疾病相关的基因变异减少了RNA编辑,激活了免疫路径. 这表明RNA编辑是常见炎症疾病的关键机制.
科学领域:
- 人类遗传学
- 分子机制
- 免疫学
背景情况:
- 鉴定遗传变异的分子机制对于理解特征和疾病至关重要.
- 基因表达和拼接的定量特征位置 (QTL) 映射已经推进了这一领域,但许多变异效应仍然不清楚.
- 通过ADAR调节的RNA编辑对于抑制双链RNA (dsRNA) 调节的先天免疫反应至关重要.
研究的目的:
- 调查ADAR介导的RNA编辑作为常见炎症疾病相关的基因变异的基础机制.
- 识别和表征cis-RNA编辑QTLs (edQTLs) 以及它们在疾病相关遗传信号中的丰富.
- 探索炎症疾病风险变体,dSRNA编辑和干扰素反应之间的关系.
主要方法:
- 在49个人类组织中识别和表征30319个cis-RNA编辑QTLs (edQTLs).
- 用全基因组关联研究 (GWAS) 对自身免疫和免疫介导疾病的信号进行edQTL的丰富分析.
- 对具有疾病风险位置的edQTL进行局部化分析,以确定特定的dsRNA和转录.
主要成果:
- 在炎症疾病的GWAS信号中显著丰富edQTLs.
- 定位免疫性dRNA,包括来自Alu元素和cis-natural反意义转录的dRNA.
- 表明炎症疾病风险变异与dSRNA编辑减少和干扰素反应相关.
结论:
- 通过ADAR调节的RNA编辑是常见炎症疾病相关的基因变异的重要机制.
- 由疾病相关变体减少dRNA编辑导致干扰素反应和炎症.
- 细胞dSRNA编辑和感知是常见炎症疾病中被低估的机制.
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