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:	Jacqueline Milet, Gregory Nuel, Laurence Watier, David Courtin, Yousri Slaoui, Paul Senghor, Florence Migot-Nabias, Oumar Gaye, André Garcia
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0e40c85525214170a95b5bf46fe1c11c
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spelling	oai:doaj.org-article:0e40c85525214170a95b5bf46fe1c11c2021-12-02T20:20:02ZGenome wide linkage study, using a 250K SNP map, of Plasmodium falciparum infection and mild malaria attack in a Senegalese population.1932-620310.1371/journal.pone.0011616https://doaj.org/article/0e40c85525214170a95b5bf46fe1c11c2010-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20657648/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Multiple 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=5x10(-5) and 9x10(-5) respectively), and between the 20p11q11 region and the prevalence of parasite density in asymptomatic children (empirical p-value=1.5x10(-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=3.7x10(-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.Jacqueline MiletGregory NuelLaurence WatierDavid CourtinYousri SlaouiPaul SenghorFlorence Migot-NabiasOumar GayeAndré GarciaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 7, p e11616 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jacqueline Milet Gregory Nuel Laurence Watier David Courtin Yousri Slaoui Paul Senghor Florence Migot-Nabias Oumar Gaye André Garcia Genome wide linkage study, using a 250K SNP map, of Plasmodium falciparum infection and mild malaria attack in a Senegalese population.
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=5x10(-5) and 9x10(-5) respectively), and between the 20p11q11 region and the prevalence of parasite density in asymptomatic children (empirical p-value=1.5x10(-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=3.7x10(-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.
format	article
author	Jacqueline Milet Gregory Nuel Laurence Watier David Courtin Yousri Slaoui Paul Senghor Florence Migot-Nabias Oumar Gaye André Garcia
author_facet	Jacqueline Milet Gregory Nuel Laurence Watier David Courtin Yousri Slaoui Paul Senghor Florence Migot-Nabias Oumar Gaye André Garcia
author_sort	Jacqueline Milet
title	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_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_sort	genome wide linkage study, using a 250k snp map, of plasmodium falciparum infection and mild malaria attack in a senegalese population.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/0e40c85525214170a95b5bf46fe1c11c
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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.

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