Unraveling Inflammatory Responses using Systems Genetics and Gene-Environment Interactions in Macrophages
| Autor: | Peter S. Gargalovic, Isaac M. Neuhaus, Charles R. Farber, Hong Xiu Qi, Matteo Pellegrini, Calvin Pan, Roumyana Yordanova, Todd G. Kirchgessner, Nam Che, Brian J. Bennett, Aldons J. Lusis, Adonisa Mutukulu, Luz D. Orozco, Anatole Ghazalpour, Ping-Zi Wen, Nathan O. Siemers |
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| Rok vydání: | 2012 |
| Předmět: |
Lipopolysaccharides
Male Candidate gene Lipopolysaccharide Cells Quantitative Trait Loci Inbred Strains Inflammation Mice Inbred Strains Quantitative trait locus Biology Medical and Health Sciences General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Species Specificity medicine Genetics Macrophage Animals 2.1 Biological and endogenous factors Aetiology Association mapping Gene Cells Cultured 030304 developmental biology 0303 health sciences Cultured Biochemistry Genetics and Molecular Biology(all) Macrophages Systems Biology Inflammatory and immune system Human Genome Biological Sciences Specific Pathogen-Free Organisms chemistry Gene Knockdown Techniques Expression quantitative trait loci Gene-Environment Interaction medicine.symptom 030217 neurology & neurosurgery Biotechnology Developmental Biology |
| Zdroj: | Cell, vol 151, iss 3 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2012.08.043 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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