title: Genetic determination and linkage mapping of Plasmodium falciparum malaria related traits in Senegal.
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.
authors.affiliation: Institut Pasteur, Unité de Génétique des Maladies Infectieuses et Autoimmunes, Paris, France. anavaj@pasteur.fr
authors.forename: Anavaj
authors.initials: A
authors.lastname: Sakuntabhai
authors.forename: Rokhaya
authors.initials: R
authors.lastname: Ndiaye
authors.forename: Isabelle
authors.initials: I
authors.lastname: Casadémont
authors.forename: Chayanon
authors.initials: C
authors.lastname: Peerapittayamongkol
authors.forename: Chayanon
authors.initials: C
authors.lastname: Peerapittayamonkol
authors.forename: Christophe
authors.initials: C
authors.lastname: Rogier
authors.forename: Patricia
authors.initials: P
authors.lastname: Tortevoye
authors.forename: Adama
authors.initials: A
authors.lastname: Tall
authors.forename: Richard
authors.initials: R
authors.lastname: Paul
authors.forename: Chairat
authors.initials: C
authors.lastname: Turbpaiboon
authors.forename: Waraphon
authors.initials: W
authors.lastname: Phimpraphi
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Trape
authors.forename: André
authors.initials: A
authors.lastname: Spiegel
authors.forename: Simon
authors.initials: S
authors.lastname: Heath
authors.forename: Odile
authors.initials: O
authors.lastname: Mercereau-Puijalon
authors.forename: Alioune
authors.initials: A
authors.lastname: Dieye
authors.forename: Cécile
authors.initials: C
authors.lastname: Julier
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D005006:Ethnicity / Q000235:genetics; D005190:Family; D015894:Genome, Human; D006801:Humans; D016778:Malaria, Falciparum / Q000235:genetics*; D010641:Phenotype; D019655:Quantitative Trait, Heritable; D012044:Regression Analysis; D012424:Rural Population; D012675:Senegal