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Genome Wide Linkage Study, Using a 250K SNP Map, of Plasmodium falciparum Infection and Mild Malaria Attack in a Senegalese Population

Multiple factors are involved in the variability of host's response to P. falciparum infection, like the intensity and seasonality of malaria transmission, the virulence of parasite and host characteristics like age or genetic make-up. Although admitted nowadays, the involvement of host genetic...

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Autores principales: Milet, Jacqueline, Nuel, Gregory, Watier, Laurence, Courtin, David, Slaoui, Yousri, Senghor, Paul, Migot-Nabias, Florence, Gaye, Oumar, Garcia, André
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904701/
https://www.ncbi.nlm.nih.gov/pubmed/20657648
http://dx.doi.org/10.1371/journal.pone.0011616
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author Milet, Jacqueline
Nuel, Gregory
Watier, Laurence
Courtin, David
Slaoui, Yousri
Senghor, Paul
Migot-Nabias, Florence
Gaye, Oumar
Garcia, André
author_facet Milet, Jacqueline
Nuel, Gregory
Watier, Laurence
Courtin, David
Slaoui, Yousri
Senghor, Paul
Migot-Nabias, Florence
Gaye, Oumar
Garcia, André
author_sort Milet, Jacqueline
collection PubMed
description Multiple factors are involved in the variability of host's response to P. falciparum infection, like the intensity and seasonality of malaria transmission, the virulence of parasite and host characteristics like age or genetic make-up. Although admitted nowadays, the involvement of host genetic factors remains unclear. Discordant results exist, even concerning the best-known malaria resistance genes that determine the structure or function of red blood cells. Here we report on a genome-wide linkage and association study for P. falciparum infection intensity and mild malaria attack among a Senegalese population of children and young adults from 2 to 18 years old. A high density single nucleotide polymorphisms (SNP) genome scan (Affimetrix GeneChip Human Mapping 250K-nsp) was performed for 626 individuals: i.e. 249 parents and 377 children out of the 504 ones included in the follow-up. The population belongs to a unique ethnic group and was closely followed-up during 3 years. Genome-wide linkage analyses were performed on four clinical and parasitological phenotypes and association analyses using the family based association tests (FBAT) method were carried out in regions previously linked to malaria phenotypes in literature and in the regions for which we identified a linkage peak. Analyses revealed three strongly suggestive evidences for linkage: between mild malaria attack and both the 6p25.1 and the 12q22 regions (empirical p-value = 5×10(−5) and 9×10(−5) respectively), and between the 20p11q11 region and the prevalence of parasite density in asymptomatic children (empirical p-value = 1.5×10(−4)). Family based association analysis pointed out one significant association between the intensity of plasmodial infection and a polymorphism located in ARHGAP26 gene in the 5q31–q33 region (p-value = 3.7×10(−5)). This study identified three candidate regions, two of them containing genes that could point out new pathways implicated in the response to malaria infection. Furthermore, we detected one gene associated with malaria infection in the 5q31–q33 region.
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spelling pubmed-29047012010-07-23 Genome Wide Linkage Study, Using a 250K SNP Map, of Plasmodium falciparum Infection and Mild Malaria Attack in a Senegalese Population Milet, Jacqueline Nuel, Gregory Watier, Laurence Courtin, David Slaoui, Yousri Senghor, Paul Migot-Nabias, Florence Gaye, Oumar Garcia, André PLoS One Research Article Multiple factors are involved in the variability of host's response to P. falciparum infection, like the intensity and seasonality of malaria transmission, the virulence of parasite and host characteristics like age or genetic make-up. Although admitted nowadays, the involvement of host genetic factors remains unclear. Discordant results exist, even concerning the best-known malaria resistance genes that determine the structure or function of red blood cells. Here we report on a genome-wide linkage and association study for P. falciparum infection intensity and mild malaria attack among a Senegalese population of children and young adults from 2 to 18 years old. A high density single nucleotide polymorphisms (SNP) genome scan (Affimetrix GeneChip Human Mapping 250K-nsp) was performed for 626 individuals: i.e. 249 parents and 377 children out of the 504 ones included in the follow-up. The population belongs to a unique ethnic group and was closely followed-up during 3 years. Genome-wide linkage analyses were performed on four clinical and parasitological phenotypes and association analyses using the family based association tests (FBAT) method were carried out in regions previously linked to malaria phenotypes in literature and in the regions for which we identified a linkage peak. Analyses revealed three strongly suggestive evidences for linkage: between mild malaria attack and both the 6p25.1 and the 12q22 regions (empirical p-value = 5×10(−5) and 9×10(−5) respectively), and between the 20p11q11 region and the prevalence of parasite density in asymptomatic children (empirical p-value = 1.5×10(−4)). Family based association analysis pointed out one significant association between the intensity of plasmodial infection and a polymorphism located in ARHGAP26 gene in the 5q31–q33 region (p-value = 3.7×10(−5)). This study identified three candidate regions, two of them containing genes that could point out new pathways implicated in the response to malaria infection. Furthermore, we detected one gene associated with malaria infection in the 5q31–q33 region. Public Library of Science 2010-07-15 /pmc/articles/PMC2904701/ /pubmed/20657648 http://dx.doi.org/10.1371/journal.pone.0011616 Text en Milet et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Milet, Jacqueline
Nuel, Gregory
Watier, Laurence
Courtin, David
Slaoui, Yousri
Senghor, Paul
Migot-Nabias, Florence
Gaye, Oumar
Garcia, André
Genome Wide Linkage Study, Using a 250K SNP Map, of Plasmodium falciparum Infection and Mild Malaria Attack in a Senegalese Population
title Genome Wide Linkage Study, Using a 250K SNP Map, of Plasmodium falciparum Infection and Mild Malaria Attack in a Senegalese Population
title_full Genome Wide Linkage Study, Using a 250K SNP Map, of Plasmodium falciparum Infection and Mild Malaria Attack in a Senegalese Population
title_fullStr Genome Wide Linkage Study, Using a 250K SNP Map, of Plasmodium falciparum Infection and Mild Malaria Attack in a Senegalese Population
title_full_unstemmed Genome Wide Linkage Study, Using a 250K SNP Map, of Plasmodium falciparum Infection and Mild Malaria Attack in a Senegalese Population
title_short Genome Wide Linkage Study, Using a 250K SNP Map, of Plasmodium falciparum Infection and Mild Malaria Attack in a Senegalese Population
title_sort genome wide linkage study, using a 250k snp map, of plasmodium falciparum infection and mild malaria attack in a senegalese population
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904701/
https://www.ncbi.nlm.nih.gov/pubmed/20657648
http://dx.doi.org/10.1371/journal.pone.0011616
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