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

Leffler, Ellen M, Band, Gavin, Busby, George B J, Kivinen, Katja, Le, Quang Si, Clarke, Geraldine M, Bojang, Kalifa A, Conway, David J, Jallow, Muminatou, Sisay-Joof, Fatoumatta, Bougouma, Edith C, Mangano, Valentina D, Modiano, David, Sirima, Sodiomon B, Achidi, Eric, Apinjoh, Tobias O, Marsh, Kevin, Ndila, Carolyne M, Peshu, Norbert, Williams, Thomas N, Drakeley, Chris, Manjurano, Alphaxard, Reyburn, Hugh, Riley, Eleanor, Kachala, David, Molyneux, Malcolm E, Nyirongo, Vysaul, Taylor, Terrie, Thornton, Nicole, Tilley, Louise, Grimsley, Shane, Drury, Eleanor, Stalker, Jim, Cornelius, Victoria, Hubbart, Christina, Jeffreys, Anna E, Rowlands, Kate, Rockett, Kirk A, Spencer, Chris C A and Kwiatkowski, Dominic P (2017) 'Resistance to malaria through structural variation of red blood cell invasion receptors.'. Science, Vol 356, Issue 6343, eaam6393.

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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. [Abstract copyright: Copyright © 2017, American Association for the Advancement of Science.]

Item Type: Article
Subjects: QU Biochemistry > Genetics > QU 460 Genomics. Proteomics
QU Biochemistry > Proteins. Amino Acids. Peptides > QU 55 Proteins
QY Clinical Pathology > Blood. Blood Chemistry > QY 402 Cellular elements
QY Clinical Pathology > Blood. Blood Chemistry > QY 450 Blood chemistry
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1126/science.aam6393
SWORD Depositor: JISC Pubrouter
Depositing User: JISC Pubrouter
Date Deposited: 12 Jul 2017 11:23
Last Modified: 06 Feb 2018 13:14
URI: http://archive.lstmed.ac.uk/id/eprint/7169

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