Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

The protective effect of sickle cell haemoglobin against severe malaria depends on parasite genotype

View ORCID ProfileGavin Band, Ellen M. Leffler, Muminatou Jallow, Fatoumatta Sisay-Joof, Carolyne M. Ndila, View ORCID ProfileAlexander W. Macharia, Christina Hubbart, Anna E. Jeffreys, Kate Rowlands, Thuy Nguyen, Sonia M. Goncalves, Cristina V. Ariani, Jim Stalker, View ORCID ProfileRichard D. Pearson, View ORCID ProfileRoberto Amato, Eleanor Drury, Giorgio Sirugo, Umberto D’Alessandro, Kalifa A. Bojang, Kevin Marsh, View ORCID ProfileNorbert Peshu, View ORCID ProfileDavid J. Conway, Thomas N. Williams, View ORCID ProfileKirk A. Rockett, Dominic P. Kwiatkowski
doi: https://doi.org/10.1101/2021.03.30.437659
Gavin Band
1Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
2Wellcome Sanger Institute, Hinxton, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Gavin Band
  • For correspondence: gavin.band@well.ox.ac.uk
Ellen M. Leffler
2Wellcome Sanger Institute, Hinxton, Cambridge, UK
3Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112-5330
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Muminatou Jallow
4Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Atlantic Boulevard, Fajara, The Gambia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fatoumatta Sisay-Joof
4Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Atlantic Boulevard, Fajara, The Gambia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carolyne M. Ndila
5KEMRI-Wellcome Trust Research Programme, CGMRC, PO Box 230-80108, Kenya
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alexander W. Macharia
5KEMRI-Wellcome Trust Research Programme, CGMRC, PO Box 230-80108, Kenya
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Alexander W. Macharia
Christina Hubbart
1Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anna E. Jeffreys
1Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kate Rowlands
1Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thuy Nguyen
2Wellcome Sanger Institute, Hinxton, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sonia M. Goncalves
2Wellcome Sanger Institute, Hinxton, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cristina V. Ariani
2Wellcome Sanger Institute, Hinxton, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jim Stalker
2Wellcome Sanger Institute, Hinxton, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard D. Pearson
1Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
2Wellcome Sanger Institute, Hinxton, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Richard D. Pearson
Roberto Amato
2Wellcome Sanger Institute, Hinxton, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Roberto Amato
Eleanor Drury
2Wellcome Sanger Institute, Hinxton, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Giorgio Sirugo
4Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Atlantic Boulevard, Fajara, The Gambia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Umberto D’Alessandro
4Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Atlantic Boulevard, Fajara, The Gambia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kalifa A. Bojang
4Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Atlantic Boulevard, Fajara, The Gambia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kevin Marsh
5KEMRI-Wellcome Trust Research Programme, CGMRC, PO Box 230-80108, Kenya
6Centre for Global Health Tropical Medicine, University of Oxford, Oxford, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Norbert Peshu
5KEMRI-Wellcome Trust Research Programme, CGMRC, PO Box 230-80108, Kenya
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Norbert Peshu
David J. Conway
4Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Atlantic Boulevard, Fajara, The Gambia
7London School of Hygiene and Tropical Medicine, Keppel Street, London, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for David J. Conway
Thomas N. Williams
5KEMRI-Wellcome Trust Research Programme, CGMRC, PO Box 230-80108, Kenya
8Department of Infectious Diseases, Imperial College Faculty of Medicine, London W21NY, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kirk A. Rockett
1Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
2Wellcome Sanger Institute, Hinxton, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Kirk A. Rockett
Dominic P. Kwiatkowski
1Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
2Wellcome Sanger Institute, Hinxton, Cambridge, UK
8Department of Infectious Diseases, Imperial College Faculty of Medicine, London W21NY, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Host genetic factors can confer resistance against malaria, raising the question of whether this has led to evolutionary adaptation of parasite populations. In this study we investigated the correlation between host and parasite genetic variation in 4,171 Gambian and Kenya children ascertained with severe malaria due to Plasmodium falciparum. We identified a strong association between sickle haemoglobin (HbS) in the host and variation in three regions of the parasite genome, including nonsynonymous variants in the acyl-CoA synthetase family member PfACS8 on chromosome 2, in a second region of chromosome 2, and in a region containing structural variation on chromosome 11. The HbS-associated parasite alleles are in strong linkage disequilibrium and have frequencies which 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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted March 31, 2021.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
The protective effect of sickle cell haemoglobin against severe malaria depends on parasite genotype
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
The protective effect of sickle cell haemoglobin against severe malaria depends on parasite genotype
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, Sonia M. Goncalves, Cristina V. Ariani, Jim Stalker, Richard D. Pearson, Roberto Amato, Eleanor Drury, Giorgio Sirugo, Umberto D’Alessandro, Kalifa A. Bojang, Kevin Marsh, Norbert Peshu, David J. Conway, Thomas N. Williams, Kirk A. Rockett, Dominic P. Kwiatkowski
bioRxiv 2021.03.30.437659; doi: https://doi.org/10.1101/2021.03.30.437659
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
The protective effect of sickle cell haemoglobin against severe malaria depends on parasite genotype
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, Sonia M. Goncalves, Cristina V. Ariani, Jim Stalker, Richard D. Pearson, Roberto Amato, Eleanor Drury, Giorgio Sirugo, Umberto D’Alessandro, Kalifa A. Bojang, Kevin Marsh, Norbert Peshu, David J. Conway, Thomas N. Williams, Kirk A. Rockett, Dominic P. Kwiatkowski
bioRxiv 2021.03.30.437659; doi: https://doi.org/10.1101/2021.03.30.437659

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genetics
Subject Areas
All Articles
  • Animal Behavior and Cognition (2653)
  • Biochemistry (5286)
  • Bioengineering (3696)
  • Bioinformatics (15824)
  • Biophysics (7279)
  • Cancer Biology (5633)
  • Cell Biology (8118)
  • Clinical Trials (138)
  • Developmental Biology (4782)
  • Ecology (7548)
  • Epidemiology (2059)
  • Evolutionary Biology (10604)
  • Genetics (7746)
  • Genomics (10163)
  • Immunology (5223)
  • Microbiology (13962)
  • Molecular Biology (5399)
  • Neuroscience (30878)
  • Paleontology (217)
  • Pathology (883)
  • Pharmacology and Toxicology (1527)
  • Physiology (2262)
  • Plant Biology (5035)
  • Scientific Communication and Education (1045)
  • Synthetic Biology (1399)
  • Systems Biology (4156)
  • Zoology (814)