IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v602y2022i7895d10.1038_s41586-021-04288-3.html
   My bibliography  Save this article

Malaria protection due to sickle haemoglobin depends on parasite genotype

Author

Listed:
  • Gavin Band

    (University of Oxford
    Wellcome Sanger Institute
    Li Ka Shing Centre for Health and Information Discovery, University of Oxford)

  • Ellen M. Leffler

    (Wellcome Sanger Institute
    University of Utah School of Medicine)

  • Muminatou Jallow

    (Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine
    Edward Francis Small Teaching Hospital (formerly Royal Victoria Teaching Hospital))

  • Fatoumatta Sisay-Joof

    (Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine)

  • Carolyne M. Ndila

    (KEMRI-Wellcome Trust Research Programme)

  • Alexander W. Macharia

    (KEMRI-Wellcome Trust Research Programme)

  • Christina Hubbart

    (University of Oxford)

  • Anna E. Jeffreys

    (University of Oxford)

  • Kate Rowlands

    (University of Oxford)

  • Thuy Nguyen

    (Wellcome Sanger Institute)

  • Sónia Gonçalves

    (Wellcome Sanger Institute)

  • Cristina V. Ariani

    (Wellcome Sanger Institute)

  • Jim Stalker

    (Wellcome Sanger Institute)

  • Richard D. Pearson

    (Wellcome Sanger Institute
    Li Ka Shing Centre for Health and Information Discovery, University of Oxford)

  • Roberto Amato

    (Wellcome Sanger Institute)

  • Eleanor Drury

    (Wellcome Sanger Institute)

  • Giorgio Sirugo

    (Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine
    University of Pennsylvania School of Medicine)

  • Umberto d’Alessandro

    (Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine)

  • Kalifa A. Bojang

    (Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine)

  • Kevin Marsh

    (KEMRI-Wellcome Trust Research Programme
    Nuffield Department of Medicine, University of Oxford)

  • Norbert Peshu

    (KEMRI-Wellcome Trust Research Programme)

  • Joseph W. Saelens

    (Duke University School of Medicine)

  • Mahamadou Diakité

    (University of Sciences, Techniques, and Technologies of Bamako)

  • Steve M. Taylor

    (Duke University School of Medicine
    Duke University)

  • David J. Conway

    (Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine
    London School of Hygiene and Tropical Medicine)

  • Thomas N. Williams

    (KEMRI-Wellcome Trust Research Programme
    Imperial College London)

  • Kirk A. Rockett

    (University of Oxford
    Wellcome Sanger Institute)

  • Dominic P. Kwiatkowski

    (University of Oxford
    Wellcome Sanger Institute
    Li Ka Shing Centre for Health and Information Discovery, University of Oxford)

Abstract

Host genetic factors can confer resistance against malaria1, raising the question of whether this has led to evolutionary adaptation of parasite populations. Here we searched for association between candidate host and parasite genetic variants in 3,346 Gambian and Kenyan children with severe malaria caused by Plasmodium falciparum. We identified a strong association between sickle haemoglobin (HbS) in the host and three regions of the parasite genome, which is not explained by population structure or other covariates, and which is replicated in additional samples. The HbS-associated alleles include nonsynonymous variants in the gene for the acyl-CoA synthetase family member2–4 PfACS8 on chromosome 2, in a second region of chromosome 2, and in a region containing structural variation on chromosome 11. The alleles are in strong linkage disequilibrium and have frequencies that covary with the frequency of HbS across populations, in particular being much more common in Africa than other parts of the world. The estimated protective effect of HbS against severe malaria, as determined by comparison of cases with population controls, varies greatly according to the parasite genotype at these three loci. These findings open up a new avenue of enquiry into the biological and epidemiological significance of the HbS-associated polymorphisms in the parasite genome and the evolutionary forces that have led to their high frequency and strong linkage disequilibrium in African P. falciparum populations.

Suggested Citation

  • Gavin Band & Ellen M. Leffler & Muminatou Jallow & Fatoumatta Sisay-Joof & Carolyne M. Ndila & Alexander W. Macharia & Christina Hubbart & Anna E. Jeffreys & Kate Rowlands & Thuy Nguyen & Sónia Gonçal, 2022. "Malaria protection due to sickle haemoglobin depends on parasite genotype," Nature, Nature, vol. 602(7895), pages 106-111, February.
  • Handle: RePEc:nat:nature:v:602:y:2022:i:7895:d:10.1038_s41586-021-04288-3
    DOI: 10.1038/s41586-021-04288-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-021-04288-3
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/s41586-021-04288-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Eva Stadler & Mohamed Maiga & Lukas Friedrich & Vandana Thathy & Claudia Demarta-Gatsi & Antoine Dara & Fanta Sogore & Josefine Striepen & Claude Oeuvray & Abdoulaye A. Djimdé & Marcus C. S. Lee & Lau, 2023. "Propensity of selecting mutant parasites for the antimalarial drug cabamiquine," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:602:y:2022:i:7895:d:10.1038_s41586-021-04288-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.