Genome-block expression-assisted association studies discover malaria resistance genes in Anopheles gambiae.
Proc Natl Acad Sci U S A
; 110(51): 20675-80, 2013 Dec 17.
Article
em En
| MEDLINE
| ID: mdl-24297936
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plasmodium falciparum
/
Genoma
/
Proteínas de Insetos
/
Polimorfismo de Nucleotídeo Único
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Imunidade Inata
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Anopheles
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
País/Região como assunto:
Africa
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article