Genetic diversity in human erythrocyte pyruvate kinase

J. Berghout (1) , S. Higgins (2) , C. Loucoubar (3) , Anavaj Sakuntabhai (3, 4) , Kevin C. Kain (2) , Philippe Gros (1)

1 McGill University = Université McGill [Montréal, Canada]
2 University of Toronto
3 Pathogénie Virale
4 Mahidol University [Bangkok]

Previously, we have shown that pyruvate kinase, liver and red cell isoform (PKLR) deficiency protects mice in vivo against blood-stage malaria, and observed that reduced PKLR function protects human erythrocytes against Plasmodium falciparum replication ex vivo. Here, we have sequenced the human PKLR gene in 387 individuals from malaria-endemic and other regions in order to assess genetic variability in different geographical regions and ethnic groups. Rich genetic diversity was detected in PKLR, including 59 single-nucleotide polymorphisms and several loss-of-function variants (frequency 1.5%). Haplotype distribution and allele frequency varied considerably with geography. Neutrality testing suggested positive selection of the genein the sub-Saharan African and Pakistan populations. It is possible that such positive selection involves the malarial parasite.

Domains: Genetics

J. Berghout, S. Higgins, C. Loucoubar, Anavaj Sakuntabhai, Kevin C. Kain, et al.. Genetic diversity in human erythrocyte pyruvate kinase. Genes and Immunity, 2012, 13 (1), pp.98-102. ⟨10.1038/gene.2011.54⟩. ⟨pasteur-02069000⟩