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.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Gat-Viks I,Chevrier N,Wilentzik R,Eisenhaure T,Raychowdhury R,Steuerman Y,Shalek AK,Hacohen N,Amit I,Regev Adoi
10.1038/nbt.2519subject
Has Abstractpub_date
2013-04-01 00:00:00pages
342-9issue
4eissn
1087-0156issn
1546-1696pii
nbt.2519journal_volume
31pub_type
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