Resistance to malaria through structural variation of red blood cell invasion receptors.


Leffler, EM; Band, G; Busby, GBJ; Kivinen, K; Le, QS; Clarke, GM; Bojang, KA; Conway, DJ; Jallow, M; Sisay-Joof, F; Bougouma, EC; Mangano, VD; Modiano, D; Sirima, SB; Achidi, E; Apinjoh, TO; Marsh, K; Ndila, CM; Peshu, N; Williams, TN; Drakeley, C; Manjurano, A; Reyburn, H; Riley, E; Kachala, D; Molyneux, M; Nyirongo, V; Taylor, T; Thornton, N; Tilley, L; Grimsley, S; Drury, E; Stalker, J; Cornelius, V; Hubbart, C; Jeffreys, AE; Rowlands, K; Rockett, KA; Spencer, CCA; Kwiatkowski, DP; Malaria Genomic Epidemiology Network, ; (2017) Resistance to malaria through structural variation of red blood cell invasion receptors. Science (New York, NY). ISSN 0036-8075 DOI: 10.1126/science.aam6393

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Abstract

The malaria parasite Plasmodium falciparum invades human red blood cells via 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 risen 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.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Faculty of Infectious and Tropical Diseases > Dept of Disease Control
Research Centre: Malaria Centre
PubMed ID: 28522690
Web of Science ID: 403327400028
URI: http://researchonline.lshtm.ac.uk/id/eprint/3928285

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