title: Genetic diversity in human erythrocyte pyruvate kinase.
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.
authors.affiliation: Department of Biochemistry, McGill University, Complex Traits Group, Montreal, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Berghout
authors.forename: S
authors.initials: S
authors.lastname: Higgins
authors.forename: C
authors.initials: C
authors.lastname: Loucoubar
authors.forename: A
authors.initials: A
authors.lastname: Sakuntabhai
authors.forename: K C
authors.initials: KC
authors.lastname: Kain
authors.forename: P
authors.initials: P
authors.lastname: Gros
mesh_terms: D000595:Amino Acid Sequence; D004912:Erythrocytes / Q000201:enzymology*; D023061:Gene Order; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008288:Malaria / Q000201:enzymology / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D011487:Protein Conformation; D011770:Pyruvate Kinase / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D011770:Pyruvate Kinase