A novel locus of resistance to severe malaria in a region of ancient balancing selection.

dc.contributor.authorBand, G.
dc.contributor.authorRockett, K.A.
dc.contributor.authorSpencer, C.C.A.
dc.contributor.authorJohnson, K.J.
dc.contributor.authorKoram, K.A.
dc.contributor.authorWilson, M.D.
dc.contributor.authorAgbenyega, T.
dc.contributor.authorMalaria Genomic Epidemiology Network
dc.date.accessioned2018-09-11T08:58:02Z
dc.date.available2018-09-11T08:58:02Z
dc.date.issued2015-09
dc.description.abstractAbstract 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 studies. 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 chimpanzees. Taken together with previous observations on the malaria-protective role of blood group O, 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.en_US
dc.identifier.otherVolume: 526
dc.identifier.otherhttps://dx.doi.org/ 10.1038/nature15390
dc.identifier.urihttp://ugspace.ug.edu.gh/handle/123456789/24040
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.subjectGeneticsen_US
dc.subjectBiologyen_US
dc.subjectBalancing selectionen_US
dc.subjectHaplotypeen_US
dc.subjectA majoren_US
dc.subjectMalariaen_US
dc.subjectPlasmodium falciparumen_US
dc.titleA novel locus of resistance to severe malaria in a region of ancient balancing selection.en_US
dc.typeArticleen_US

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