结合性基因组分析与功能相关的RNA修饰单核酸多态
Xinran Liu1, Sai Zhu1, Xueqi Liu1
1Department of Nephropathy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, China.
Heliyon
|November 7, 2024
概括
与RNA修饰相关的单核酸多态 (RNAm-SNPs) 与功能有关. 这些遗传变异影响基因表达和蛋白质水平,影响脏疾病的发展,并提供潜在的治疗点.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 腎臟病學 (nephrology) 是一種醫學專業.
背景情况:
- 越来越多地认识到RNA修饰在功能和疾病发病过程中的作用.
- 将RNA修饰与脏疾病联系在一起的精确机制在很大程度上仍未被探索.
- 全基因组关联研究 (GWAS) 已经确定了与功能和RNA修饰相关的遗传位置.
研究的目的:
- 研究与RNA修饰相关的单核酸多态 (RNAm-SNPs) 与估计的淋巴细胞过率 (eGFR) 之间的关联.
- 通过表达量性特征位置 (eQTL) 和蛋白质量性特征位置 (pQTL) 分析,探索已识别的RNAm-SNP的功能影响.
- 通过孟德尔随机化 (MR) 评估RNAm-SNP相关基因表达,蛋白质水平和功能之间的因果关系.
主要方法:
- 对252个mRNA-SNP与eGFR的关联分析.
- 血液细胞和血中的cis-eQTL和cis-pQTL分析.
- 门德尔随机化 (MR) 分析以评估因果关系.
主要成果:
- 确定了与各种RNA修饰 (m6A,m1A,A-to-I,m5C,m7G,m5U) 相关的252个RNAm-SNP,它们都与eGFR有显著的相关性.
- 在血液细胞中47.22%的RNAm-SNP中观察到显著的cis-eQTL效应,在血中28.57%的cis-pQTL效应.
- 在RNAm-SNP相关基因表达,循环蛋白水平和eGFR下降之间建立了因果关系,其中一些基因/蛋白质 (例如CDK10,SDCCAG8) 与脏疾病有关.
结论:
- 这项研究确立了RNAm-SNP与功能之间的显著关联.
- 通过RNA修饰,RNAm-SNP会影响基因和蛋白质的表达,从而导致功能障碍.
- 这些发现为病的遗传基础提供了新的见解,将遗传风险与RNA修饰联系起来,并建议潜在的治疗途径.
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