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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; 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; Kwiatkowski, Dominic P.
Afiliación
  • Leffler EM; Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
  • Band G; Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
  • Busby GBJ; Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
  • Kivinen K; Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
  • Le QS; Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
  • Clarke GM; Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
  • Bojang KA; Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
  • Conway DJ; Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
  • Jallow M; Medical Research Council Unit, Atlantic Boulevard, Fajara, Post Office Box 273, The Gambia.
  • Sisay-Joof F; Medical Research Council Unit, Atlantic Boulevard, Fajara, Post Office Box 273, The Gambia.
  • Bougouma EC; Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
  • Mangano VD; Medical Research Council Unit, Atlantic Boulevard, Fajara, Post Office Box 273, The Gambia.
  • Modiano D; Royal Victoria Teaching Hospital, Independence Drive, Post Office Box 1515, Banjul, The Gambia.
  • Sirima SB; Medical Research Council Unit, Atlantic Boulevard, Fajara, Post Office Box 273, The Gambia.
  • Achidi E; Centre National de Recherche et de Formation sur le Paludisme (CNRFP), 01 BP 2208 Ouagadougou 01, Burkina Faso.
  • Apinjoh TO; University of Rome La Sapienza, Piazzale Aldo Moro 5, 00185 Rome, Italy.
  • Marsh K; University of Rome La Sapienza, Piazzale Aldo Moro 5, 00185 Rome, Italy.
  • Ndila CM; Centre National de Recherche et de Formation sur le Paludisme (CNRFP), 01 BP 2208 Ouagadougou 01, Burkina Faso.
  • Peshu N; Department of Medical Laboratory Sciences, University of Buea, Post Office Box 63, Buea, South West Region, Cameroon.
  • Williams TN; Department of Biochemistry and Molecular Biology, University of Buea, Post Office Box 63, Buea, South West Region, Cameroon.
  • Drakeley C; Kenyan Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Post Office Box 230-80108, Kilifi, Kenya.
  • Manjurano A; Nuffield Department of Medicine, NDM Research Building, Roosevelt Drive, Headington, Oxford OX3 7FZ, UK.
  • Reyburn H; Kenyan Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Post Office Box 230-80108, Kilifi, Kenya.
  • Riley E; Kenyan Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Post Office Box 230-80108, Kilifi, Kenya.
  • Kachala D; Kenyan Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Post Office Box 230-80108, Kilifi, Kenya.
  • Molyneux M; Faculty of Medicine, Department of Medicine, Imperial College, Exhibition Road, London SW7 2AZ, UK.
  • Nyirongo V; Joint Malaria Programme, Kilimanjaro Christian Medical Centre, Post Office Box 2228, Moshi, Tanzania.
  • Taylor T; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
  • Thornton N; Joint Malaria Programme, Kilimanjaro Christian Medical Centre, Post Office Box 2228, Moshi, Tanzania.
  • Tilley L; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
  • Grimsley S; National Institute for Medical Research, Mwanza Research Centre, Mwanza City, Tanzania.
  • Drury E; Joint Malaria Programme, Kilimanjaro Christian Medical Centre, Post Office Box 2228, Moshi, Tanzania.
  • Stalker J; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
  • Cornelius V; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
  • Hubbart C; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital, College of Medicine, Post Office Box 30096, Chichiri, Blantyre 3, Malawi.
  • Jeffreys AE; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital, College of Medicine, Post Office Box 30096, Chichiri, Blantyre 3, Malawi.
  • Rowlands K; Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.
  • Rockett KA; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital, College of Medicine, Post Office Box 30096, Chichiri, Blantyre 3, Malawi.
  • Spencer CCA; Blantyre Malaria Project, Queen Elizabeth Central Hospital, College of Medicine, Post Office Box 30096, Chichiri, Blantyre 3, Malawi.
  • Kwiatkowski DP; College of Osteopathic Medicine, Michigan State University, East Lansing, MI 48824, USA.
Science ; 356(6343)2017 06 16.
Article en En | MEDLINE | ID: mdl-28522690
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glicoforinas / Modelos Moleculares / Malaria Falciparum / Eritrocitos / Resistencia a la Enfermedad / Interacciones Huésped-Parásitos Tipo de estudio: Prognostic_studies Límite: Adult / Child / Humans País/Región como asunto: Africa Idioma: En Revista: Science Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glicoforinas / Modelos Moleculares / Malaria Falciparum / Eritrocitos / Resistencia a la Enfermedad / Interacciones Huésped-Parásitos Tipo de estudio: Prognostic_studies Límite: Adult / Child / Humans País/Región como asunto: Africa Idioma: En Revista: Science Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos