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Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):20675-80. doi: 10.1073/pnas.1321024110. Epub 2013 Dec 2.

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

Author information

1
Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019.

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.

KEYWORDS:

chromosomal domains; gene expression; genomics; synteny; traits

PMID:
24297936
PMCID:
PMC3870758
DOI:
10.1073/pnas.1321024110
[Indexed for MEDLINE]
Free PMC Article

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