title: Genome-block expression-assisted association studies discover malaria resistance genes in Anopheles gambiae.
abstract: The malaria parasite-resistance island (PRI) of the African mosquito vector, Anopheles gambiae, was mapped to five genomic regions containing 80 genes, using coexpression patterns of genomic blocks. High-throughput sequencing identified 347 nonsynonymous single-nucleotide polymorphisms within these genes in mosquitoes from malaria-endemic areas in Kenya. Direct association studies between nonsynonymous single-nucleotide polymorphisms and Plasmodium falciparum infection identified three naturally occurring genetic variations in each of three genes (An. gambiae adenosine deaminase, fibrinogen-related protein 30, and fibrinogen-related protein 1) that were associated significantly with parasite infection. A role for these genes in the resistance phenotype was confirmed by RNA interference knockdown assays. Silencing fibrinogen-related protein 30 increased parasite infection significantly, whereas ablation of fibrinogen-related protein 1 transcripts resulted in mosquitoes nearly free of parasites. The discovered genes and single-nucleotide polymorphisms are anticipated to be useful in the development of tools for malaria control in endemic areas in Africa.
authors.affiliation: Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.forename: Genwei
authors.initials: G
authors.lastname: Zhang
authors.forename: John I
authors.initials: JI
authors.lastname: Githure
authors.forename: Guiyun
authors.initials: G
authors.lastname: Yan
authors.forename: Anthony A
authors.initials: AA
authors.lastname: James
mesh_terms: D000818:Animals; D000852:Anopheles / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D020868:Gene Silencing; D016678:Genome / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics*; D019476:Insect Proteins / Q000235:genetics / Q000276:immunology; D007630:Kenya; D010963:Plasmodium falciparum / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide
chemical_list: D019476:Insect Proteins
keywords: chromosomal domains; gene expression; genomics; synteny; traits