期刊
SCIENCE
卷 356, 期 6343, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aam6393
关键词
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资金
- Wellcome Trust [WT077383/Z/05/Z, 090770/Z/09/Z, 090532/Z/09/Z, 098051, 076934/Z/05/Z, 091758/Z/10/Z, 084538]
- Bill & Melinda Gates Foundation through the Foundations of the National Institutes of Health as part of the Grand Challenges in Global Health Initiative [566]
- Medical Research Council (MRC) [G0600718, G0600230, MR/M006212/1]
- Wellcome Trust Career Development Fellowship [097364/Z/11/Z]
- European Community's Seventh Framework Programme (FP7) [242095-EVIMalaR]
- Central African Network for Tuberculosis, HIV/AIDS, and Malaria (CANTAM) - European and Developing Countries Clinical Trials Partnership (EDCTP)
- MRC [G9901439]
- Wellcome Trust Research Leave Fellowship
- MLW core grant
- Istituto Pasteur-Fondazione Cenci Bolognetti, BioMalPar, and Evimalar (European Community FP6, FP7)
- MRC [G0600718, G0600230, MC_UP_A900_1118, MR/M006212/1] Funding Source: UKRI
- Medical Research Council [MR/M006212/1, G0600718, G0600230] Funding Source: researchfish
- Wellcome Trust [204911/Z/16/Z] Funding Source: researchfish
The malaria parasite Plasmodium falciparum invades human red blood cells by a series of interactions between host and parasite surface proteins. By analyzing genome sequence data from human populations, including 1269 individuals from sub-Saharan Africa, we identify a diverse array of large copy-number variants affecting the host invasion receptor genes GYPA and GYPB. We find that a nearby association with severe malaria is explained by a complex structural rearrangement involving the loss of GYPB and gain of two GYPB-A hybrid genes, which encode a serologically distinct blood group antigen known as Dantu. This variant reduces the risk of severe malaria by 40% and has recently increased in frequency in parts of Kenya, yet it appears to be absent from west Africa. These findings link structural variation of red blood cell invasion receptors with natural resistance to severe malaria.
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