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Title: Genetic determination and linkage mapping of Plasmodium falciparum malaria related traits in Senegal
Authors: Anavaj Sakuntabhai
Rokhaya Ndiaye
Isabelle Casadémont
Chayanon Peerapittayamonkol
Christopher Rogier
Patricia Tortevoye
Adama Tall
Richard Paul
Chairat Turbpaiboon
Waraphon Phimpraphi
Jean Francois Trape
André Spiegel
Simon Heath
Odile Mercereau-Puijalon
Alioune Dieye
Cécile Julier
Institut Pasteur, Paris
Institut Pasteur de Dakar
IMTSSA Institut de Medecine Tropicale du Service de Sante des Armees
Institut de Recherche pour le Developpement Dakar
Hopital d'Instruction des Armees du Val de Grace
Centre National de Genotypage
CNRS Centre National de la Recherche Scientifique
Universite Cheikh Anta Diop
Mahidol University
Keywords: Agricultural and Biological Sciences;Biochemistry, Genetics and Molecular Biology
Issue Date: 23-Apr-2008
Citation: PLoS ONE. Vol.3, No.4 (2008)
Abstract: Plasmodium falciparum malaria episodes may vary considerably in their severity and clinical manifestations. There is good evidence that host genetic factors contribute to this variability. To date, most genetic studies aiming at the identification of these genes have used a case/ control study design for severe malaria, exploring specific candidate genes. Here, we performed a family-based genetic study of falciparum malaria related phenotypes in two independent longitudinal survey cohorts, as a first step towards the identification of genes and mechanisms involved in the outcome of infection. We studied two Senegalese villages, Dielmo and Ndiop that differ in ethnicity, malaria transmission and endemicity. We performed genome-scan linkage analysis of several malaria-related phenotypes both during clinical attacks and asymptomatic infection. We show evidence for a strong genetic contribution to both the number of clinical falciparum malaria attacks and the asymptomatic parasite density. The asymptomatic parasite density showed linkage to chromosome 5q31 (LOD = 2.26, empirical p = 0.0014, Dielmo), confirming previous findings in other studies. Suggestive linkage values were also obtained at three additional chromosome regions: the number of clinical malaria attacks on chromosome 5p15 (LOD = 2.57, empirical p = 0.001, Dielmo) and 13q13 (LOD = 2.37, empirical p = 0.0014 Dielmo), and the maximum parasite density during asymptomatic infection on chromosome 12q21 (LOD = 3.1, empirical p<10-4, Ndiop). While regions of linkage show little overlap with genes known to be involved in severe malaria, the four regions appear to overlap with regions linked to asthma or atopy related traits, suggesting that common immune related pathways may be involved. © 2008 Sakuntabhai et al.
ISSN: 19326203
Appears in Collections:Scopus 2006-2010

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