5'UTR突变的大规模并行屏幕识别了影响神经发育障碍基因翻译和蛋白质生产的变异
Stephen P Plassmeyer1,2, Colin P Florian1,2, Michael J Kasper1,2
1Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
medRxiv : the preprint server for health sciences
|November 14, 2023
概括
我们开发了一种高通量试验,用于选与自闭症相关的5'未翻译区域 (UTR) 突变. 该方法识别了影响蛋白质生产的功能突变,有助于诊断和理解神经发育障碍.
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:
- 未翻译区域 (UTR) 的新突变与自闭症等神经发育障碍有关.
- 仅从序列数据预测这些UTR突变的功能影响是具有挑战性的.
研究的目的:
- 开发和验证一种高通量试验,用于选自闭症患者中发现的5'UTR变异的影响.
- 研究5'UTRs细胞类型特定的调节作用,特别是在神经元中.
主要方法:
- 一个高通量测定被设计用于评估997个5'UTR变异的转录和转化效应.
- 用患者衍生细胞系和体内神经元模型来验证研究结果.
- 记者测试被用来测量蛋白质翻译的变化.
主要成果:
- 该试验确定了100多个潜在的功能5'UTR突变.
- 这些突变被证实会改变患者衍生细胞中的蛋白质生产.
- 观察到细胞类型特定的调节差异,神经元显示出明显的5'UTR调节.
- 发现了影响神经元中已知的综合性自闭症基因 (LRRC4,ZNF644) 的患者突变.
结论:
- 开发的试验提供了一种新的方法来评估5'UTR突变在不同细胞类型的功能影响.
- 一些神经发育障碍可能是由5'UTR中的功能变异引起的.
- 研究结果表明,5'UTRs在与自闭症病因相关的神经元调节中的特定作用.
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