Imperial College London
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Professor Thomas N Williams

Faculty of Medicine, Department of Surgery & Cancer

Chair in Haemoglobinopathy Research
 
 
 
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Contact

 

tom.williams Website

 
 
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Location

 

Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Band:2021:10.1038/s41586-021-04288-3,
author = {Band, G and Leffler, EM and Jallow, M and Sisay-Joof, F and Ndila, CM and Macharia, AW and Hubbart, C and Jeffreys, AE and Rowlands, K and Nguyen, T and Gonçalves, S and Ariani, CV and Stalker, J and Pearson, RD and Amato, R and Drury, E and Sirugo, G and d'Alessandro, U and Bojang, KA and Marsh, K and Peshu, N and Saelens, JW and Diakité, M and Taylor, SM and Conway, DJ and Williams, TN and Rockett, KA and Kwiatkowski, DP},
doi = {10.1038/s41586-021-04288-3},
journal = {Nature},
pages = {1--23},
title = {Malaria protection due to sickle haemoglobin depends on parasite genotype},
url = {http://dx.doi.org/10.1038/s41586-021-04288-3},
volume = {602},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Band,G
AU  - Leffler,EM
AU  - Jallow,M
AU  - Sisay-Joof,F
AU  - Ndila,CM
AU  - Macharia,AW
AU  - Hubbart,C
AU  - Jeffreys,AE
AU  - Rowlands,K
AU  - Nguyen,T
AU  - Gonçalves,S
AU  - Ariani,CV
AU  - Stalker,J
AU  - Pearson,RD
AU  - Amato,R
AU  - Drury,E
AU  - Sirugo,G
AU  - d'Alessandro,U
AU  - Bojang,KA
AU  - Marsh,K
AU  - Peshu,N
AU  - Saelens,JW
AU  - Diakité,M
AU  - Taylor,SM
AU  - Conway,DJ
AU  - Williams,TN
AU  - Rockett,KA
AU  - Kwiatkowski,DP
DO  - 10.1038/s41586-021-04288-3
EP  - 23
PY  - 2021///
SN  - 0028-0836
SP  - 1
TI  - Malaria protection due to sickle haemoglobin depends on parasite genotype
T2  - Nature
UR  - http://dx.doi.org/10.1038/s41586-021-04288-3
UR  - https://www.ncbi.nlm.nih.gov/pubmed/34883497
UR  - https://www.nature.com/articles/s41586-021-04288-3
UR  - http://hdl.handle.net/10044/1/94064
VL  - 602
ER  -
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