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

Ellen M. Leffler | Zendy; Gavin Band | Zendy; George B. J. Busby | Zendy; Katja Kivinen | Zendy; Si Quang Le | Zendy; Geraldine M Clarke | Zendy; Kalifa Bojang | Zendy; David J. Conway | Zendy; Muminatou Jallow | Zendy; Fatoumatta Sisay-Joof | Zendy; Edith C. Bougouma | Zendy; Valentina Mangano | Zendy; David Modiano | Zendy; Sodiomon B. Sirima | Zendy; Eric Achidi | Zendy; Tobias O. Apinjoh | Zendy; Kevin Marsh | Zendy; Carolyne Ndila | Zendy; Norbert Peshu | Zendy; Thomas N. Williams | Zendy; Chris Drakeley | Zendy; Alphaxard Manjurano | Zendy; Hugh Reyburn | Zendy; Eleanor M. Riley | Zendy; David Kachala | Zendy; Malcolm E. Molyneux | Zendy; Vysaul Nyirongo | Zendy; Terrie E. Taylor | Zendy; Nicole Thornton | Zendy; Louise Tilley | Zendy; Shane Grimsley | Zendy; Eleanor Drury | Zendy; Jim Stalker | Zendy; Victoria Cornelius | Zendy; Christina Hubbart | Zendy; Anna E. Jeffreys | Zendy; Kate Rowlands | Zendy; Kirk A. Rockett | Zendy; Chris C. A. Spencer | Zendy; Dominic Kwiatkowski | Zendy

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

Author(s) -

Ellen M. Leffler,

Gavin Band,

George B. J. Busby,

Katja Kivinen,

Si Quang Le,

Geraldine M Clarke,

Kalifa Bojang,

David J. Conway,

Muminatou Jallow,

Fatoumatta Sisay-Joof,

Edith C. Bougouma,

Valentina Mangano,

David Modiano,

Sodiomon B. Sirima,

Eric Achidi,

Tobias O. Apinjoh,

Kevin Marsh,

Carolyne Ndila,

Norbert Peshu,

Thomas N. Williams,

Chris Drakeley,

Alphaxard Manjurano,

Hugh Reyburn,

Eleanor M. Riley,

David Kachala,

Malcolm E. Molyneux,

Vysaul Nyirongo,

Terrie E. Taylor,

Nicole Thornton,

Louise Tilley,

Shane Grimsley,

Eleanor Drury,

Jim Stalker,

Victoria Cornelius,

Christina Hubbart,

Anna E. Jeffreys,

Kate Rowlands,

Kirk A. Rockett,

Chris C. A. Spencer,

Dominic Kwiatkowski

Publication year - 2017

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.aam6393

Subject(s) - malaria , plasmodium falciparum , biology , parasite hosting , gene , structural variation , receptor , genome , red blood cell , virology , genetics , plasmodium (life cycle) , immunology , world wide web , computer science

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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