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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.

Original publication

DOI

10.1126/science.aam6393

Type

Journal article

Journal

Science (New York, N.Y.)

Publication Date

06/2017

Volume

356

Addresses

Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.

Keywords

Malaria Genomic Epidemiology Network, Erythrocytes, Humans, Malaria, Falciparum, Glycophorin, Receptors, Cell Surface, Protein Structure, Secondary, Gene Frequency, Genome, Human, Models, Molecular, Adult, Child, Africa South of the Sahara, Host-Parasite Interactions, DNA Copy Number Variations, Disease Resistance