Genome-block expression-assisted association studies discover malaria resistance genes in Anopheles gambiae Article

Li, J, Wang, X, Zhang, G et al. (2013). Genome-block expression-assisted association studies discover malaria resistance genes in Anopheles gambiae . 110(51), 20675-20680. 10.1073/pnas.1321024110

cited authors

  • Li, J; Wang, X; Zhang, G; Githure, JI; Yan, G; James, AA

fiu authors

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 fibrinogenrelated 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.

publication date

  • December 17, 2013

Digital Object Identifier (DOI)

start page

  • 20675

end page

  • 20680

volume

  • 110

issue

  • 51