Battle Alexis, Khan Zia, Wang Sidney H, Mitrano Amy, Ford Michael J, Pritchard Jonathan K, Gilad Yoav
Department of Genetics, Stanford University, Stanford, CA 94305, USA. Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
Science. 2015 Feb 6;347(6222):664-7. doi: 10.1126/science.1260793. Epub 2014 Dec 18.
The phenotypic consequences of expression quantitative trait loci (eQTLs) are presumably due to their effects on protein expression levels. Yet the impact of genetic variation, including eQTLs, on protein levels remains poorly understood. To address this, we mapped genetic variants that are associated with eQTLs, ribosome occupancy (rQTLs), or protein abundance (pQTLs). We found that most QTLs are associated with transcript expression levels, with consequent effects on ribosome and protein levels. However, eQTLs tend to have significantly reduced effect sizes on protein levels, which suggests that their potential impact on downstream phenotypes is often attenuated or buffered. Additionally, we identified a class of cis QTLs that affect protein abundance with little or no effect on messenger RNA or ribosome levels, which suggests that they may arise from differences in posttranslational regulation.
表达数量性状基因座（eQTL）的表型后果可能归因于它们对蛋白质表达水平的影响。然而，包括eQTL在内的遗传变异对蛋白质水平的影响仍知之甚少。为了解决这个问题，我们绘制了与eQTL、核糖体占有率（rQTL）或蛋白质丰度（pQTL）相关的遗传变异图谱。我们发现，大多数QTL与转录本表达水平相关，进而影响核糖体和蛋白质水平。然而，eQTL对蛋白质水平的效应大小往往显著降低，这表明它们对下游表型的潜在影响通常会减弱或受到缓冲。此外，我们鉴定出一类顺式QTL，它们影响蛋白质丰度，但对信使RNA或核糖体水平几乎没有影响，这表明它们可能源于翻译后调控的差异。
