Genetic determination and linkage mapping of Plasmodium falciparum malaria related traits in Senegal.
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.
Sakuntabhai
Anavaj
A
Institut Pasteur, Unité de Génétique des Maladies Infectieuses et Autoimmunes, Paris, France. anavaj@pasteur.fr
Ndiaye
Rokhaya
R
Casadémont
Isabelle
I
Peerapittayamongkol
Chayanon
C
Peerapittayamonkol
Chayanon
C
Rogier
Christophe
C
Tortevoye
Patricia
P
Tall
Adama
A
Paul
Richard
R
Turbpaiboon
Chairat
C
Phimpraphi
Waraphon
W
Trape
Jean-Francois
JF
Spiegel
André
A
Heath
Simon
S
Mercereau-Puijalon
Odile
O
Dieye
Alioune
A
Julier
Cécile
C
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