在45个突然不明原因死亡病例中解读分子解剖结果:从编码区域到未翻译区域
Shouyu Wang1, Jianghua Du1, Qi Shen1
1Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, China.
International journal of legal medicine
|September 12, 2024
概括
未翻译区域 (UTR) 的遗传变异可能会使个体倾向于突然无法解释的死亡 (SUD). 这项研究在心脏基因中发现了三种高度可靠的致病性UTR变异,为SUD病例的分子尸检提供了一种新方法.
科学领域:
- 心血管遗传学 心血管遗传学
- 分子尸体解剖学 分子尸体解剖学
- 突然无法解释的死亡 (SUD) 研究研究
背景情况:
- 突然无法解释的死亡 (SUD) 影响年轻,看似健康的个体,通常是由于心律失常.
- 目前尚不完全了解SUD的遗传基础,目前的分子尸检主要集中在编码区域.
- 未翻译区域 (UTR) 的基因变异越来越多地与人类疾病有关,这表明它们在SUD中的潜在作用.
研究的目的:
- 研究未翻译区域 (UTR) 变异在突然不明原因死亡 (SUD) 的遗传倾向中的作用.
- 在SUD病例中识别与心脏病相关的基因中的潜在致病性UTR变异.
- 在SUD分子解剖中开发和验证优先级和功能性注释UTR变异的策略.
主要方法:
- 分析了来自45个SUD病例的外体数据,以确定UTR变异.
- 严格的过策略应用于244个与心脏相关的基因.
- 功能测试用于验证候选变异对基因转录活动的影响.
- 对基因约束指标,不耐受性指数和剂量敏感性的评估.
主要成果:
- 在SCO2,CALM2和TBX3基因的UTR中识别了三种高度可靠的致病变体.
- 功能性测试证实了这些变异对基因转录活性的影响.
- 考虑基因特异性指标来评估异常基因表达的后果.
结论:
- 未翻译区域 (UTR) 变异是突然不明原因死亡 (SUD) 易感性的重要,以前未被充分探索的因素.
- 对于UTR变异优先级和功能注释的实用策略可以增强分子尸体解剖解释.
- 这种方法可以提高诊断产量和对SUD的遗传贡献的理解.
相关概念视频
01:31Translation
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
02:27Nonsense-mediated mRNA Decay
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
02:24Ribosome Profiling
Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique helps...
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique helps...
01:31Translation
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life