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...

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Main Authors: Anavaj Sakuntabhai, Rokhaya Ndiaye, Isabelle Casadémont, Chayanon Peerapittayamongkol, Christophe 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
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2008-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2295258?pdf=render
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author Anavaj Sakuntabhai
Rokhaya Ndiaye
Isabelle Casadémont
Chayanon Peerapittayamongkol
Christophe 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
author_facet Anavaj Sakuntabhai
Rokhaya Ndiaye
Isabelle Casadémont
Chayanon Peerapittayamongkol
Christophe 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
author_sort Anavaj Sakuntabhai
collection DOAJ
description 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.
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spelling doaj.art-845db98f19934ca19e02117e717be4c82022-12-21T17:46:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-0134e200010.1371/journal.pone.0002000Genetic determination and linkage mapping of Plasmodium falciparum malaria related traits in Senegal.Anavaj SakuntabhaiRokhaya NdiayeIsabelle CasadémontChayanon PeerapittayamongkolChristophe RogierPatricia TortevoyeAdama TallRichard PaulChairat TurbpaiboonWaraphon PhimpraphiJean-Francois TrapeAndré SpiegelSimon HeathOdile Mercereau-PuijalonAlioune DieyeCécile JulierPlasmodium 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.http://europepmc.org/articles/PMC2295258?pdf=render
spellingShingle Anavaj Sakuntabhai
Rokhaya Ndiaye
Isabelle Casadémont
Chayanon Peerapittayamongkol
Christophe 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
Genetic determination and linkage mapping of Plasmodium falciparum malaria related traits in Senegal.
PLoS ONE
title Genetic determination and linkage mapping of Plasmodium falciparum malaria related traits in Senegal.
title_full Genetic determination and linkage mapping of Plasmodium falciparum malaria related traits in Senegal.
title_fullStr Genetic determination and linkage mapping of Plasmodium falciparum malaria related traits in Senegal.
title_full_unstemmed Genetic determination and linkage mapping of Plasmodium falciparum malaria related traits in Senegal.
title_short Genetic determination and linkage mapping of Plasmodium falciparum malaria related traits in Senegal.
title_sort genetic determination and linkage mapping of plasmodium falciparum malaria related traits in senegal
url http://europepmc.org/articles/PMC2295258?pdf=render
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