TY - JOUR
T1 - Malaria
T2 - Looking for selection signatures in the human PKLR gene region
AU - Machado, Patrícia
AU - Pereira, Rui
AU - Rocha, Ana Mafalda
AU - Manco, Licínio
AU - Fernandes, Natércia
AU - Miranda, Juliana
AU - Ribeiro, Letícia
AU - Do Rosário, Virgílio E.
AU - Amorim, António
AU - Gusmão, Leonor
AU - Arez, Ana Paula
PY - 2010/6
Y1 - 2010/6
N2 - 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.
AB - 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.
KW - Human malaria
KW - Molecular markers
KW - PKLR
KW - Pyruvate kinase-deficiency
KW - Selection signatures
UR - http://www.scopus.com/inward/record.url?scp=77952609107&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2141.2010.08165.x
DO - 10.1111/j.1365-2141.2010.08165.x
M3 - Article
C2 - 20377593
AN - SCOPUS:77952609107
SN - 0007-1048
VL - 149
SP - 775
EP - 784
JO - British Journal Of Haematology
JF - British Journal Of Haematology
IS - 5
ER -