Identification of three single nucleotide polymorphisms in Anopheles gambiae immune signaling genes that are associated with natural Plasmodium falciparum infection

Abstract

<p>Abstract</p> <p>Background</p> <p>Laboratory studies have demonstrated that a variety of immune signaling pathways regulate malaria parasite infection in <it>Anopheles gambiae</it>, the primary vector species in Africa.</p> <p>Methods</p> <p>To begin to understand the importance of these associations under natural conditions, an association mapping approach was adopted to determine whether single nucleotide polymorphisms (SNPs) in selected immune signaling genes in <it>A. gambiae </it>collected in Mali were associated with the phenotype of <it>Plasmodium falciparum </it>infection.</p> <p>Results</p> <p>Three SNPs were identified in field-collected mosquitoes that were associated with parasite infection in molecular form-dependent patterns: two were detected in the <it>Toll5B </it>gene and one was detected in the gene encoding insulin-like peptide 3 precursor. In addition, one infection-associated <it>Toll5B </it>SNP was in linkage disequilibrium with a SNP in sequence encoding a mitogen-activated protein kinase that has been associated with Toll signaling in mammalian cells. Both <it>Toll5B </it>SNPs showed divergence from Hardy-Weinberg equilibrium, suggesting that selection pressure(s) are acting on these loci.</p> <p>Conclusions</p> <p>Seven of these eight infection-associated and linked SNPs alter codon frequency or introduce non-synonymous changes that would be predicted to alter protein structure and, hence, function, suggesting that these SNPs could alter immune signaling and responsiveness to parasite infection.</p