Genome-block expression-assisted association studies discover malaria resistance genes in Anopheles gambiae
Genome-block expression-assisted association studies discover malaria resistance genes in Anopheles gambiae
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DOI：
10.1073/pnas.1321024110
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发表时间：
2013-12-17
影响因子：
11.1
通讯作者：
James, Anthony A.
中科院分区：
文献类型：
--
作者：
Li, Jun;Wang, Xiaohong;James, Anthony A.
利用基因组区块的共表达模式，将非洲按蚊媒介冈比亚按蚊的抗疟原虫岛(PRI)定位到包含80个基因的5个基因组区域。高通量测序在肯尼亚疟疾流行地区的蚊子中发现了这些基因中的347个非同义单核苷酸多态。非同义单核苷酸多态与恶性疟原虫感染之间的直接关联研究发现，三个基因中的每一个都有三个自然发生的遗传变异。冈比亚的腺苷脱氨酶、纤维蛋白原相关蛋白30和纤维蛋白原相关蛋白1)与寄生虫感染显著相关。通过RNA干扰敲除实验证实了这些基因在抗性表型中的作用。沉默纤维蛋白原相关蛋白30显著增加寄生虫感染，而去除纤维蛋白原相关蛋白1转录本导致蚊子几乎没有寄生虫。这些已发现的基因和单核苷酸多态预计将有助于开发非洲疟疾流行地区的疟疾控制工具。
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.