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 desig...
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th-mahidol.187452018-07-12T09:19:03Z Genetic determination and linkage mapping of Plasmodium falciparum malaria related traits in Senegal 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 Inserm 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 Agricultural and Biological Sciences Biochemistry, Genetics and Molecular Biology 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. 2018-07-12T02:14:54Z 2018-07-12T02:14:54Z 2008-04-23 Article PLoS ONE. Vol.3, No.4 (2008) 10.1371/journal.pone.0002000 19326203 2-s2.0-44349104689 https://repository.li.mahidol.ac.th/handle/123456789/18745 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=44349104689&origin=inward |
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Agricultural and Biological Sciences Biochemistry, Genetics and Molecular Biology 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 Genetic determination and linkage mapping of Plasmodium falciparum malaria related traits in Senegal |
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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. |
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Institut Pasteur, Paris |
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Institut Pasteur, Paris 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 |
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Article |
author |
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 |
author_sort |
Anavaj Sakuntabhai |
title |
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_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_sort |
genetic determination and linkage mapping of plasmodium falciparum malaria related traits in senegal |
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2018 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/18745 |
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1763497477225316352 |