在人体组织中剖析昼夜节律的遗传结构,使用定量昼夜偏差得分
1Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, 925 Bloom Walk, Los Angeles, CA, 90089, USA.
Genome biology
|September 26, 2025
概括
我们开发了一种关于昼夜扰乱的新分子测量方法,识别了654种与昼夜节律相关的遗传变异 (Circ-SNPs). 这些发现表明,对于昼夜和睡眠障碍的潜在药物重用.
科学领域:
- 遗传学 是一个遗传学.
- 时间生物学 时间生物学
- 分子生物学分子生物学
背景情况:
- 循环节律调节重要的生理和行为过程.
- 影响昼夜节律和睡眠特征的遗传因素尚未完全理解.
研究的目的:
- 介绍了一种针对昼夜干扰的新型分子测量方法.
- 确定与昼夜节律调节相关的遗传变异.
- 探索昼夜和睡眠障碍的潜在治疗点.
主要方法:
- 使用人类组织的基因表达数据开发了一个"昼夜偏差得分".
- 进行全基因组关联研究以确定与昼夜偏差得分相关的单核酸多态 (SNP).
- 分析了已识别的SNP的位置和潜在的监管作用.
- 利用DrugBank来评估与已识别的SNP相关的基因的药用性.
主要成果:
- 确定了654个与分子昼夜干扰相关的SNP (Circ-SNP).
- Circ-SNP在小肠和上腺丰富,在X染色体上具有显著的比例.
- 确定了122个Circ-regulator基因,其中18个是163种现有的药物所针对的,其中6种用于睡眠障碍.
- 环-SNP经常位于转录的3'末端附近,表明转录后调节.
结论:
- 昼夜偏差得分提供了一个关于昼夜干扰的分子量度.
- 发现了参与昼夜节律调节的新型遗传变异 (Circ-SNPs) 和基因 (Circ-regulators).
- 这些发现支持重新利用现有药物的潜力来治疗与生理节律相关的睡眠障碍.
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