| Literature DB >> 28522690 |
Ellen M Leffler1,2, Gavin Band1,2, George B J Busby1, Katja Kivinen2, Quang Si Le1, Geraldine M Clarke1, Kalifa A Bojang3, David J Conway3,4, Muminatou Jallow3,5, Fatoumatta Sisay-Joof3, Edith C Bougouma6, Valentina D Mangano7, David Modiano7, Sodiomon B Sirima6, Eric Achidi8, Tobias O Apinjoh9, Kevin Marsh10,11, Carolyne M Ndila10, Norbert Peshu10, Thomas N Williams10,12, Chris Drakeley13,14, Alphaxard Manjurano13,14,15, Hugh Reyburn13,14, Eleanor Riley14, David Kachala16, Malcolm Molyneux16,17, Vysaul Nyirongo16, Terrie Taylor18,19, Nicole Thornton20, Louise Tilley20, Shane Grimsley20, Eleanor Drury2, Jim Stalker2, Victoria Cornelius1, Christina Hubbart1, Anna E Jeffreys1, Kate Rowlands1, Kirk A Rockett1,2, Chris C A Spencer21, Dominic P Kwiatkowski21,2.
Abstract
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.Entities:
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Year: 2017 PMID： 28522690 PMCID： PMC5575826 DOI： 10.1126/science.aam6393
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728