功能性3'-UTR变异识别影响酒精使用障碍和相关特征的监管机制
Andy B Chen1,2, Xuhong Yu1, Kriti S Thapa3
1Department of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
bioRxiv : the preprint server for biology
|February 19, 2024
概括
基因3'未翻译区域 (3'-UTRs) 的功能变异会影响酒精使用障碍 (AUD) 的遗传性. 与炎症相关的基因活动会影响饮酒倾向.
科学领域:
- 遗传学 遗传学 是一个
- 神经科学是一个神经科学.
- 分子生物学分子生物学
背景情况:
- 全基因组关联研究 (GWAS) 识别了饮酒和酒精使用障碍 (AUD) 的遗传位置.
- 在这些位点内识别功能变异仍然是一个挑战.
- 3'未翻译区域 (3-UTRs) 在基因调节中起着关键作用.
研究的目的:
- 为了确定与AUD和酒精消费相关的3-UTRs中的功能遗传变异.
- 研究这些变异在基因表达和遗传性中的作用.
- 探索炎症途径与酒精消费之间的联系.
主要方法:
- 大规模并行记者测试 (MPRA) 用于测试神经母细胞瘤和微质细胞中的3-UTR变异功能.
- 整合MPRA数据与酒精特征的GWAS结果.
- 克里斯普尔抑制实验用于评估基因表达变化.
- 对差异表达基因的途径分析.
主要成果:
- 具有功能影响的3-UTR变异解释了酒精特征遗传率的更大比例.
- 具有改变3 -UTR活性的特定基因与AUD和酒精消费有关.
- 在差异表达的基因中,炎症反应途径显著丰富.
- 由MPRA衍生的3-UTR活性分层与大脑组织中的基因表达相关.
结论:
- 3 -UTRs中的遗传变异对AUD遗传性有显著的贡献.
- 特定基因的3-UTR活性的改变会影响饮酒.
- 炎症反应途径与增加酒精消费的遗传倾向有关.
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