RT Journal Article
SR Electronic
T1 Resistance to malaria through structural variation of red blood cell invasion receptors
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 083634
DO 10.1101/083634
A1 Ellen M. Leffler
A1 Gavin Band
A1 George B.J. Busby
A1 Katja Kivinen
A1 Quang Si Le
A1 Geraldine M. Clarke
A1 Kalifa A. Bojang
A1 David J. Conway
A1 Muminatou Jallow
A1 Fatoumatta Sisay-Joof
A1 Edith C. Bougouma
A1 Valentina D. Mangano
A1 David Modiano
A1 Sodiomon B. Sirima
A1 Eric Achidi
A1 Tobias O. Apinjoh
A1 Kevin Marsh
A1 Carolyne M. Ndila
A1 Norbert Peshu
A1 Thomas N. Williams
A1 Chris Drakeley
A1 Alphaxard Manjurano
A1 Hugh Reyburn
A1 Eleanor Riley
A1 David Kachala
A1 Malcolm Molyneux
A1 Vysaul Nyirongo
A1 Terrie Taylor
A1 Nicole Thornton
A1 Louise Tilley
A1 Shane Grimsley
A1 Eleanor Drury
A1 Jim Stalker
A1 Victoria Cornelius
A1 Christina Hubbart
A1 Anna E. Jeffreys
A1 Kate Rowlands
A1 Kirk A. Rockett
A1 Chris C.A. Spencer
A1 Dominic P. Kwiatkowski
A1 Malaria Genomic Epidemiology Network
YR 2017
UL http://biorxiv.org/content/early/2017/02/10/083634.abstract
AB Plasmodium falciparum invades human red blood cells by a series of interactions between host and parasite surface proteins. Here we analyse whole genome sequence data from worldwide human populations, including 765 new genomes from across sub-Saharan Africa, and identify a diverse array of large copy number variants affecting the host invasion receptor genes GYPA and GYPB. We find that a nearby reported association with severe malaria is explained by a complex structural variant that involves the loss of GYPB and gain of two hybrid genes, each with a GYPB extracellular domain and GYPA intracellular domain. This variant reduces the risk of severe malaria by 40% and has recently risen in frequency in parts of Kenya. We show that the structural variant encodes the Dantu blood group antigen, and therefore a serologically distinct red cell phenotype. These findings demonstrate that structural variation of red blood cell invasion receptors is associated with natural resistance to P. falciparum malaria.