美国哥伦比亚大学Tuuli Lappalainen、Sarah Kim-Hellmuth等研究人员合作揭示不同人体组织中基因表达的细胞类型特异性遗传调控。该项研究成果发表在2020年9月11日出版的《科学》杂志上。

研究人员表示，基因型-组织表达（GTEx）计划已在不同人类组织中鉴定出大多数基因的表达和顺式剪接数量性状位点（QTLs）。但是，这些QTLs的功能表征受到GTEx组织样品异质细胞组成的限制。

研究人员绘制了细胞类型丰度和基因型计算估计之间的相互作用，从而鉴定出七种细胞类型的相互作用QTLs，并表明细胞类型相互作用表达QTLs（eQTLs）比组织特异性顺式eQTL提供了更好的组织特异性分辨率。具有87个复杂性状的遗传关联分析显示，细胞类型相互作用QTLs发挥了作用，并且使研究人员发现了数百个以前未鉴定的共定位基因座（这些基因座会在整体组织中被掩盖）。

附：英文原文

Author: Sarah Kim-Hellmuth, Franois Aguet, Meritxell Oliva, Manuel Muoz-Aguirre, Silva Kasela, Valentin Wucher, Stephane E. Castel, Andrew R. Hamel, Ana Viuela, Amy L. Roberts, Serghei Mangul, Xiaoquan Wen, Gao Wang, Alvaro N. Barbeira, Diego Garrido-Martín, Brian B. Nadel, Yuxin Zou, Rodrigo Bonazzola, Jie Quan, Andrew Brown, Angel Martinez-Perez, José Manuel Soria, GTEx Consortium§, Gad Getz, Emmanouil T. Dermitzakis, Kerrin S. Small, Matthew Stephens, Hualin S. Xi, Hae Kyung Im, Roderic Guigó, Ayellet V. Segrè, Barbara E. Stranger, Kristin G. Ardlie, Tuuli Lappalainen

Issue&Volume: 2020/09/11

Abstract: The Genotype-Tissue Expression (GTEx) project has identified expression and splicing quantitative trait loci in cis (QTLs) for the majority of genes across a wide range of human tissues. However, the functional characterization of these QTLs has been limited by the heterogeneous cellular composition of GTEx tissue samples. We mapped interactions between computational estimates of cell type abundance and genotype to identify cell type–interaction QTLs for seven cell types and show that cell type–interaction expression QTLs (eQTLs) provide finer resolution to tissue specificity than bulk tissue cis-eQTLs. Analyses of genetic associations with 87 complex traits show a contribution from cell type–interaction QTLs and enables the discovery of hundreds of previously unidentified colocalized loci that are masked in bulk tissue.

DOI: 10.1126/science.aaz8528

Source: https://science.sciencemag.org/content/369/6509/eaaz8528