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人类蛋白质丰富性的变异和遗传控制

Linfeng Wu¹, Sophie I Candille, Yoonha Choi

¹Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.

|May 17, 2013

概括

人类蛋白质水平在个体和人群之间有很大差异,受遗传学影响. 这项研究量化了蛋白质的丰富性,揭示了遗传性特征,并确定了与蛋白质表达的新型遗传联系.

科学领域:

基因组学就是基因组学.
蛋白质组学是指蛋白质组学.
人类遗传学人类遗传学

背景情况:

基因表达变异有助于表型差异.
对人类蛋白质丰度变化及其遗传基础的理解有限.
使者RNA水平是蛋白质水平的不完美预测因转录后调节.

研究的目的:

量化不同人类个体的相对蛋白质水平.
研究蛋白质丰度的遗传性和变异性.
识别影响蛋白质水平的遗传变异 (cis-pQTLs).

主要方法:

用于蛋白质量测量的定量质谱法 (基于异标签).
从95名HapMap项目个体中分析淋巴细胞细胞系.
蛋白质组数据与DNA变异和转录组信息的整合.

主要成果:

蛋白质水平是可遗传的分子表型,具有显著的个体间,人群间和基于性别的变化.
在相同的生物路径内的蛋白质组中观察到蛋白质水平的共同变异.
鉴定cis-pQTLs,包括之前转录组研究遗漏的变体.

结论:

高通量的人类蛋白质组量化是可行的.
蛋白质丰富度变化提供了对超越mRNA水平的基因表达调节的见解.
整合蛋白质组,DNA变异和转录组数据,可以全面了解分子表型.

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