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• W1856196215 startingPage "253" @default.
• W1856196215 abstract "The high prevalence of sickle haemoglobin in Africa shows that malaria has been a major force for human evolutionary selection, but surprisingly few other polymorphisms have been proven to confer resistance to malaria in large epidemiological studies1,2,3. To address this problem, we conducted a multi-centre genome-wide association study (GWAS) of life-threatening Plasmodium falciparum infection (severe malaria) in over 11,000 African children, with replication data in a further 14,000 individuals. Here we report a novel malaria resistance locus close to a cluster of genes encoding glycophorins that are receptors for erythrocyte invasion by P. falciparum. We identify a haplotype at this locus that provides 33% protection against severe malaria (odds ratio = 0.67, 95% confidence interval = 0.60–0.76, P value = 9.5 × 10−11) and is linked to polymorphisms that have previously been shown to have features of ancient balancing selection, on the basis of haplotype sharing between humans and chimpanzees4. Taken together with previous observations on the malaria-protective role of blood group O1,2,3,5, these data reveal that two of the strongest GWAS signals for severe malaria lie in or close to genes encoding the glycosylated surface coat of the erythrocyte cell membrane, both within regions of the genome where it appears that evolution has maintained diversity for millions of years. These findings provide new insights into the host–parasite interactions that are critical in determining the outcome of malaria infection." @default.
• W1856196215 created "2016-06-24" @default.
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• W1856196215 creator A5077751896 @default.
• W1856196215 creator A5080506243 @default.
• W1856196215 date "2015-09-30" @default.
• W1856196215 modified "2023-09-30" @default.
• W1856196215 title "A novel locus of resistance to severe malaria in a region of ancient balancing selection" @default.
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• W1856196215 doi "https://doi.org/10.1038/nature15390" @default.
• W1856196215 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4629224" @default.
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• W1856196215 hasPublicationYear "2015" @default.
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