title: Malaria: looking for selection signatures in the human PKLR gene region.
abstract: 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.
authors.affiliation: Centre for Malaria and Tropical Diseases, Malaria Unit, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal. pmachado@ihmt.unl.pt
authors.forename: Patrícia
authors.initials: P
authors.lastname: Machado
authors.forename: Rui
authors.initials: R
authors.lastname: Pereira
authors.forename: Ana Mafalda
authors.initials: AM
authors.lastname: Rocha
authors.forename: Licínio
authors.initials: L
authors.lastname: Manco
authors.forename: Natércia
authors.initials: N
authors.lastname: Fernandes
authors.forename: Juliana
authors.initials: J
authors.lastname: Miranda
authors.forename: Letícia
authors.initials: L
authors.lastname: Ribeiro
authors.forename: Virgílio E
authors.initials: VE
authors.lastname: do Rosário
authors.forename: António
authors.initials: A
authors.lastname: Amorim
authors.forename: Leonor
authors.initials: L
authors.lastname: Gusmão
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Arez
mesh_terms: D044383:Black People / Q000235:genetics; D002648:Child; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D016778:Malaria, Falciparum / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011770:Pyruvate Kinase / Q000172:deficiency / Q000235:genetics*; D012641:Selection, Genetic; D044465:White People / Q000235:genetics
chemical_list: D011770:Pyruvate Kinase