Malaria: looking for selection signatures in the human PKLR gene region

Br J Haematol. 2010 Jun;149(5):775-84. doi: 10.1111/j.1365-2141.2010.08165.x. Epub 2010 Apr 4.


The genetic component of susceptibility to malaria is both complex and multigenic and the better-known protective polymorphisms are those involving erythrocyte-specific structural proteins and enzymes. In vivo and in vitro data have suggested that pyruvate kinase deficiency, which causes a nonspherocytic haemolytic anaemia, could be protective against malaria severity in humans, but this hypothesis remains to be tested. In the present study, we conducted a combined analysis of Short Tandem Repeats (STRs) and Single Nucleotide Polymorphisms (SNPs) in the pyruvate kinase-encoding gene (PKLR) and adjacent regions (chromosome 1q21) to look for malaria selective signatures in two sub-Saharan African populations from Angola and Mozambique, in several groups with different malaria infection outcome. A European population from Portugal, including a control and a pyruvate kinase-deficient group, was used for comparison. Data from STR and SNP loci spread along the PKLR gene region showed a considerably higher differentiation between African and Portuguese populations than that usually found for neutral markers. In addition, a wider region showing strong linkage disequilibrium was found in an uncomplicated malaria group, and a haplotype was found to be associated with this clinical group. Altogether, this data suggests that malaria selective pressure is acting in this genomic region.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Black People / genetics
  • Child
  • Chromosomes, Human, Pair 1 / genetics
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Linkage Disequilibrium
  • Malaria, Falciparum / genetics*
  • Microsatellite Repeats / genetics
  • Polymorphism, Single Nucleotide
  • Pyruvate Kinase / deficiency
  • Pyruvate Kinase / genetics*
  • Selection, Genetic
  • White People / genetics


  • Pyruvate Kinase