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

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Patricia Machado (Author) Other; Rui Pereira (Author) Other; Ana Mafalda Rocha (Author) Other; Licinio Manco (Author) Other; Natercia Fernandes (Author) Other; Juliana Miranda (Author) Other; Leticia Ribeiro (Author) Other; Virgilio E do Rosario (Author) Other; Antonio Amorim (Author) FCUP; Leonor Gusmao (Author) FCUP; Ana Paula Arez (Author) Other

Journal

Title: British Journal of Haematology

Vol. 149

Pages: 775-784

ISSN: 0007-1048

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 16 Citations

Scopus - 17 Citations

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

Other information

Authenticus ID: P-003-5WE

DOI: 10.1111/j.1365-2141.2010.08165.x

Abstract (EN): P>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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10