Journal article
Resistance to malaria through structural variation of red blood cell invasion receptors
- Abstract:
- Plasmodium falciparum invades erythrocytes via interactions with proteins on the host cell surface. By analyzing genome sequence data from human populations, including 1269 African individuals, we identify a diverse array of large copy number variants affecting the erythrocyte invasion receptor genes GYPA and GYPB. We find that a nearby association with severe malaria is explained by a complex structural rearrangement 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, a serologically distinct red cell phenotype. Thus structural variation of erythrocyte invasion receptors is associated with natural resistance to severe malaria.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Accepted manuscript, pdf, 2.1MB, Terms of use)
-
- Publisher copy:
- 10.1126/science.aam6393
Authors
+ Wellcome Trust
More from this funder
- Grant:
- WT077383/Z/05/Z
- Career Development Fellowship (097364/Z/11/Z
- Funding agency for:
- Spencer, C
- Publisher:
- American Association for the Advancement of Science
- Journal:
- Science More from this journal
- Volume:
- 356
- Issue:
- 6343
- Article number:
- eaam6393
- Publication date:
- 2017-06-16
- Acceptance date:
- 2017-05-08
- DOI:
- EISSN:
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1095-920
- ISSN:
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0036-8075
- Pubs id:
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pubs:693871
- UUID:
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uuid:f7f57748-c702-4b7c-bad1-ec53e0508651
- Local pid:
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pubs:693871
- Source identifiers:
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693871
- Deposit date:
-
2017-05-09
- ARK identifier:
Terms of use
- Copyright holder:
- American Association for the Advancement of Science
- Copyright date:
- 2017
- Notes:
-
Copyright © 2017 American Association for the Advancement of Science.
This is an article distributed under the terms of the Science Journals Default License. This is the accepted manuscript version of the article. The final version is available online from American Association for the Advancement of Science at: https://doi.org/10.1126/science.aam6393
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