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Genetic diversity in human erythrocyte pyruvate kinase

Genes & Immunity volume 13, pages 98–102 (2012)Cite this article

Abstract

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.

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Acknowledgements

This study was funded by a Canadian Institutes of Health Research (CIHR) Team Grant in Malaria (KCK, PG), CIHR MOP-13721 (KCK), Genome Canada through the Ontario Genomics Institute (KCK), CIHR Canada Research Chairs (KCK) and CIHR studentships (JB, SH).

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Authors and Affiliations

  1. Department of Biochemistry, McGill University, Complex Traits Group, Montreal, Canada

    J Berghout & P Gros

  2. McLaughlin-Rotman Centre for Global Health, Toronto General Hospital, University of Toronto, Toronto, Canada

    S Higgins & K C Kain

  3. Institut Pasteur, Unité de Pathogénie Virale, Paris, France

    C Loucoubar & A Sakuntabhai

  4. Center of Excellence for Vector and Vector-Borne Diseases, Faculty of Science, Mahidol University, Bangkok, Thailand

    A Sakuntabhai

Authors
  1. J Berghout
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  2. S Higgins
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  3. C Loucoubar
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  4. A Sakuntabhai
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  5. K C Kain
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  6. P Gros
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Correspondence to P Gros.

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The authors declare no conflict of interest.

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Berghout, J., Higgins, S., Loucoubar, C. et al. Genetic diversity in human erythrocyte pyruvate kinase. Genes Immun 13, 98–102 (2012). https://doi.org/10.1038/gene.2011.54

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