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Plasmodium falciparum: linkage disequilibrium between loci in chromosomes 7 and 5 and chloroquine selective pressure in Northern Nigeria

Published online by Cambridge University Press:  28 November 2001

I. S. ADAGU  and
D. C. WARHURST
I. S. ADAGU
Affiliation:
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WCIE 7HT, UK
D. C. WARHURST
Affiliation:
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WCIE 7HT, UK
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Abstract

In view of the recent discovery (Molecular Cell6, 861–871) of a (Lys76Thr) codon change in gene pfcrt on chromosome 7 which determines in vitro chloroquine resistance in Plasmodium falciparum, we have re-examined samples taken before treatment in our study in Zaria, Northern Nigeria (Parasitology119, 343–348). Drug resistance was present in 5/5 cases where the pfcrt 76Thr codon change was seen (100% positive predictive value). Drug sensitivity was found in 26/28 cases where the change was absent (93% negative predictive value). Allele pfcrt 76Thr showed strong linkage disequilibrium with pfmdr1 Tyr86 on chromosome 5, more complete than that between pfcrt and cg2 alleles situated between recombination cross-over points on chromosome 7. Physical linkage of cg2 with pfcrt may account for linkage disequilibrium between their alleles but in the case of genes pfmdr1 and pfcrt, on different chromosomes, it is likely that this is maintained epistatically through the selective pressure of chloroquine.

Keywords

linkage disequilibriumPlasmodium falciparumchloroquine resistancemalariaNigeria
Type
Research Article
Information
Parasitology , Volume 123 , Issue 3 , March 2001 , pp. 219 - 224
Copyright
© 2002 Cambridge University Press

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