Genome-wide Analysis of Host-Plasmodium yoelii Interactions Reveals Regulators of the Type I Interferon Response.

Abstract

Invading pathogens trigger specific host responses, an understanding of which might identify genes that function in pathogen recognition and elimination. In this study, we performed trans-species expression quantitative trait locus (ts-eQTL) analysis using genotypes of the Plasmodium yoelii malaria parasite and phenotypes of mouse gene expression. We significantly linked 1,054 host genes to parasite genetic loci (LOD score ≥ 3.0). Using LOD score patterns, which produced results that differed from direct expression-level clustering, we grouped host genes that function in related pathways, allowing functional prediction of unknown genes. As a proof of principle, 14 of 15 randomly selected genes predicted to function in type I interferon (IFN-I) responses were experimentally validated using overexpression, small hairpin RNA knockdown, viral infection, and/or infection of knockout mice. This study demonstrates an effective strategy for studying gene function, establishes a functional gene database, and identifies regulators in IFN-I pathways.

• Authors: Jian Wu, Baowei Cai, Wenxiang Sun, Ruili Huang, Xueqiao Liu, Meng Lin, Sittiporn Pattaradilokrat, Scott Martin, Yanwei Qi, Sethu C Nair, Silvia Bolland, Jeffrey I Cohen, Christopher P Austin, Carole A Long, Timothy G Myers, Rong-Fu Wang, Xin-Zhuan Su
• Journal: Cell reports (Cell Rep) Vol. 12 Issue 4 Pg. 661-72 (Jul 28 2015) ISSN: 2211-1247 [Electronic] United States
• PMID: 26190101 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Interferon Type I

Topics

• Animals
• Genome, Protozoan
• Genome-Wide Association Study
• Host-Parasite Interactions (genetics)
• Interferon Type I (genetics, metabolism)
• Malaria (genetics, parasitology)
• Mice
• Mice, Inbred C57BL
• Plasmodium yoelii (genetics, pathogenicity)
• Quantitative Trait Loci