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Malaria protection due to sickle haemoglobin depends on parasite genotype.

Publication ,  Journal Article
Band, G; Leffler, EM; Jallow, M; Sisay-Joof, F; Ndila, CM; Macharia, AW; Hubbart, C; Jeffreys, AE; Rowlands, K; Nguyen, T; Gonçalves, S ...
Published in: Nature
February 2022

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.

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Published In

Nature

DOI

EISSN

1476-4687

Publication Date

February 2022

Volume

602

Issue

7895

Start / End Page

106 / 111

Location

England

Related Subject Headings

  • Polymorphism, Genetic
  • Plasmodium falciparum
  • Parasites
  • Male
  • Malaria, Falciparum
  • Linkage Disequilibrium
  • Kenya
  • Humans
  • Host Adaptation
  • Hemoglobin, Sickle
 

Citation

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ICMJE
MLA
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Band, G., Leffler, E. M., Jallow, M., Sisay-Joof, F., Ndila, C. M., Macharia, A. W., … Kwiatkowski, D. P. (2022). Malaria protection due to sickle haemoglobin depends on parasite genotype. Nature, 602(7895), 106–111. https://doi.org/10.1038/s41586-021-04288-3
Band, Gavin, Ellen M. Leffler, Muminatou Jallow, Fatoumatta Sisay-Joof, Carolyne M. Ndila, Alexander W. Macharia, Christina Hubbart, et al. “Malaria protection due to sickle haemoglobin depends on parasite genotype.Nature 602, no. 7895 (February 2022): 106–11. https://doi.org/10.1038/s41586-021-04288-3.
Band G, Leffler EM, Jallow M, Sisay-Joof F, Ndila CM, Macharia AW, et al. Malaria protection due to sickle haemoglobin depends on parasite genotype. Nature. 2022 Feb;602(7895):106–11.
Band, Gavin, et al. “Malaria protection due to sickle haemoglobin depends on parasite genotype.Nature, vol. 602, no. 7895, Feb. 2022, pp. 106–11. Pubmed, doi:10.1038/s41586-021-04288-3.
Band G, Leffler EM, Jallow M, Sisay-Joof F, Ndila CM, Macharia AW, Hubbart C, Jeffreys AE, Rowlands K, Nguyen T, Gonçalves S, Ariani CV, Stalker J, Pearson RD, Amato R, Drury E, Sirugo G, d’Alessandro U, Bojang KA, Marsh K, Peshu N, Saelens JW, Diakité M, Taylor SM, Conway DJ, Williams TN, Rockett KA, Kwiatkowski DP. Malaria protection due to sickle haemoglobin depends on parasite genotype. Nature. 2022 Feb;602(7895):106–111.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

February 2022

Volume

602

Issue

7895

Start / End Page

106 / 111

Location

England

Related Subject Headings

  • Polymorphism, Genetic
  • Plasmodium falciparum
  • Parasites
  • Male
  • Malaria, Falciparum
  • Linkage Disequilibrium
  • Kenya
  • Humans
  • Host Adaptation
  • Hemoglobin, Sickle