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绘制人类细胞的基因地图

Max A Horlbeck¹, Albert Xu¹, Min Wang²

¹Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94158, USA.

|July 24, 2018

概括

这项研究使用CRISPR干扰绘制了人类遗传相互作用 (GI),揭示了基因功能和意想不到的通路联系. 这一发现确立了胃肠道地图作为了解细胞遗传学的强大工具.

科学领域:

遗传学
分子生物学
系统生物学

背景情况:

基因相互作用 (GI) 对于理解基因功能至关重要,正如在酵母中所示.
之前的人类细胞研究使用了有限的基因组,使得大规模的胃肠道测绘的可行性尚未解决.

研究的目的:

开发和实施一个CRISPR干扰平台,用于大规模的人类地理标志的定量绘制.
为功能基因组学和路径发现创建一个全面的人体肠道地图.

主要方法:

在使用CRISPR干扰平台的两种癌细胞系中,对222,784个基因对进行了系统性干扰.
对基因相互作用数据进行定量分析以建立功能性基因网络.

主要成果:

产生了大规模的人体肠道地图,成功地聚集了功能相关的基因.
赋予不良特征的基因功能,例如识别TMEM261作为电子运输链组件.
发现了新的途径关系,包括通过ATR/9-1-1途径的胆固醇生物合成和DNA损伤反应之间的联系.

结论:

人体消化道图是解剖基因功能和发现复杂生物关系的高分辨率工具.
开发的平台和生成的地图作为未来人类细胞大规模遗传景观研究的蓝图.

关键词:

关于CRISPR的研究在CRISPRi中这种病功能性基因组学基因相互作用

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