Malaria: looking for selection signatures in the human PKLR gene region

Patricia Machado (1) , Rui Pereira (2, 3) , Ana Mafalda Rocha (4) , Licínio Anco (5, 6) , Natércia Fernandes (7) , Juliana Miranda (8) , M. Letícia Ribeiro (9) , Virgílio E. Do Rosário (1) , António Amorim (2) , Leonor Gusmão (2) , Ana Paula Arez (1)

1 Malaria
2 Population Genetics
3 Instituto de Medicina Legal
4 Sequencing Service
5 Anthropology
6 Haematology
7 Faculté de Médecine [Université Eduardo Mondlane]
8 Paediatrics
9 Haematology

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.

Mots clés: Medicine

Patricia Machado, Rui Pereira, Ana Mafalda Rocha, Licínio Anco, Natércia Fernandes, et al.. Malaria: looking for selection signatures in the human PKLR gene region. British Journal of Haematology, 2010, 149 (5), pp.775. ⟨10.1111/j.1365-2141.2010.08165.x⟩. ⟨hal-00552587⟩