Malaria: looking for selection signatures in the human PKLR gene region.
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.
Machado
Patrícia
P
Centre for Malaria and Tropical Diseases, Malaria Unit, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal. pmachado@ihmt.unl.pt
Pereira
Rui
R
Rocha
Ana Mafalda
AM
Manco
Licínio
L
Fernandes
Natércia
N
Miranda
Juliana
J
Ribeiro
Letícia
L
do Rosário
Virgílio E
VE
Amorim
António
A
Gusmão
Leonor
L
Arez
Ana Paula
AP
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
D011770:Pyruvate Kinase