Deciphering molecular circuits from genetic variation underlying transcriptional responsiveness to stimuli

Irit Gat-Viks*, Nicolas Chevrier, Roni Wilentzik, Thomas Eisenhaure, Raktima Raychowdhury, Yael Steuerman, Alex K. Shalek, Nir Hacohen, Ido Amit, Aviv Regev

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Individual genetic variation affects gene responsiveness to stimuli, often by influencing complex molecular circuits. Here we combine genomic and intermediate-scale transcriptional profiling with computational methods to identify variants that affect the responsiveness of genes to stimuli (responsiveness quantitative trait loci or reQTLs) and to position these variants in molecular circuit diagrams. We apply this approach to study variation in transcriptional responsiveness to pathogen components in dendritic cells from recombinant inbred mouse strains. We identify reQTLs that correlate with particular stimuli and position them in known pathways. For example, in response to a virus-like stimulus, a trans-acting variant responds as an activator of the antiviral response; using RNA interference, we identify Rgs16 as the likely causal gene. Our approach charts an experimental and analytic path to decipher the mechanisms underlying genetic variation in circuits that control responses to stimuli.

Original languageEnglish
Pages (from-to)342-349
Number of pages8
JournalNature Biotechnology
Volume31
Issue number4
DOIs
StatePublished - Apr 2013

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