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Genome-block expression-assisted association studies discover malaria resistance genes in Anopheles gambiae
- Li, Jun, Wang, Xiaohong, Zhang, Genwei, Githure, John I., Yan, Guiyun, James, Anthony A.
- Proceedings of the National Academy of Sciences of the United States of America 2013 v.110 no.51 pp. 20675-20680
- Anopheles gambiae, Plasmodium falciparum, RNA interference, adenosine deaminase, genes, genetic variation, high-throughput nucleotide sequencing, insect vectors, malaria, parasites, phenotype, single nucleotide polymorphism, Kenya
- 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.