一种哺乳动物基因组签名由单核酸变异形成,控制转录组完整性和多样性
bioRxiv : the preprint server for biology
|September 29, 2025
概括
一个新发现的基因组特征,G-tract-AG动机,与影响基因拼接的遗传变异有关. 单核酸变体 (SNV) 破坏这些基因会改变转录异型,并可能导致遗传性疾病.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 哺乳动物基因组序列具有许多鲜为人知的功能特征.
- 基因组签名在保持转录组完整性和多样性方面发挥着至关重要的作用.
研究的目的:
- 识别和描述与遗传变异相关的新型基因组签名.
- 阐明基因拼接中这种特征的功能机制及其与遗传疾病的联系.
主要方法:
- 在哺乳动物基因组中识别G-tract-AG图案.
- 从全基因组关联研究 (GWAS) 中分析G-tract-AG动机与单核酸变体 (SNV) 之间的关联.
- 用基因型-组织表达 (GTEx) 项目的数据来确定G通道在拼接调节中的作用的功能测试.
主要成果:
- 鉴定出一种广泛演变的基因组特征,即G-tract-AG动机 (AG二核化物上游的瓜宁通道).
- 这些图案与SNV有着显著的关联,特别是在非编码区域 (NCR).
- 通过阻断第二个转化步骤,G通道抑制了相邻3'AG的剪接;破坏G通道的SNV减轻了这种抑制,产生了新的转录异型.
- 数以千计的人类G-通道因拼接定量特征位点 (sQTLs) 而被破坏,G-通道破坏性SNVs在cis中发现了大多数蛋白质编码基因,并与遗传疾病有关.
结论:
- G-tract-AG图案代表了哺乳动物进化的基因组特征,对于保持转录组完整至关重要.
- 由SNVs破坏这些动机提供了对转录多样性和遗传疾病病因学的机制性见解.
- 这项研究为与各种特征相关的非编码区域SNV的功能注释提供了一个新的框架.
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