Common Genetic Variants Modulate Pathogen-Sensing Responses in Human Dendritic Cells

Science, 2014
Mark N. Lee, Chun Ye, Alexandra-Chloé Villani, Towfique Raj, Weibo Li, Thomas M. Eisenhaure, Selina H. Imboywa, Portia I. Chipendo, F. Ann Ran, Kamil Slowikowski, Lucas D. Ward, Khadir Raddassi, Cristin McCabe, Michelle H. Lee, Irene Y. Frohlich, David A. Hafler, Manolis Kellis, Soumya Raychaudhuri, Feng Zhang, Barbara E. Stranger, Christophe O. Benoist, Philip L. De Jager, Aviv Regev, Nir Hacohen

Abstract

It is difficult to determine the mechanistic consequences of context-dependent genetic variants, some of which may be related to disease (see the Perspective by Gregersen). Two studies now report on the effects of stimulating immunological monocytes and dendritic cells with proteins that can elicit a response to bacterial or viral infection and assess the functional links between genetic variants and profiles of gene expression. M. N. Leeet al. (10.1126/science.1246980) analyzed the expression of more than 400 genes, in dendritic cells from 534 healthy subjects, which revealed how expression quantitative trait loci (eQTLs) affect gene expression within the interferon-β and the Toll-like receptor 3 and 4 pathways. Fairfax et al. (10.1126/science.1246949) performed a genome-wide analysis to show that many eQTLs affected monocyte gene expression in a stimulus- or time-specific manner.

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