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Publication : Unraveling inflammatory responses using systems genetics and gene-environment interactions in macrophages.

First Author  Orozco LD Year  2012
Journal  Cell Volume  151
Issue  3 Pages  658-70
PubMed ID  23101632 Mgi Jnum  J:346752
Mgi Id  MGI:7618847 Doi  10.1016/j.cell.2012.08.043
Citation  Orozco LD, et al. (2012) Unraveling inflammatory responses using systems genetics and gene-environment interactions in macrophages. Cell 151(3):658-70
abstractText  Many common diseases have an important inflammatory component mediated in part by macrophages. Here we used a systems genetics strategy to examine the role of common genetic variation in macrophage responses to inflammatory stimuli. We examined genome-wide transcript levels in macrophages from 92 strains of the Hybrid Mouse Diversity Panel. We exposed macrophages to control media, bacterial lipopolysaccharide (LPS), or oxidized phospholipids. We performed association mapping under each condition and identified several thousand expression quantitative trait loci (eQTL), gene-by-environment interactions, and eQTL "hot spots" that specifically control LPS responses. We used siRNA knockdown of candidate genes to validate an eQTL hot spot in chromosome 8 and identified the gene 2310061C15Rik as a regulator of inflammatory responses in macrophages. We have created a public database where the data presented here can be used as a resource for understanding many common inflammatory traits that are modeled in the mouse and for the dissection of regulatory relationships between genes.
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