3 research outputs found
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 (LODâ=â2.26, empirical pâ=â0.0014, 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 (LODâ=â2.57, empirical pâ=â0.001, Dielmo) and 13q13 (LODâ=â2.37, empirical pâ=â0.0014 Dielmo), and the maximum parasite density during asymptomatic infection on chromosome 12q21 (LODâ=â3.1, empirical p<10â4, 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
Genome scan linkage analysis results by the variance component method (SOLAR) in Dielmo, PFA, the number of clinical episodes of <i>P. falciparum</i>. mxPFD and mePFD, the maximum and mean <i>P. falciparum</i> parasite densities during clinical episodes.
<p>PtPF, the prevalence of asymptomatic <i>P. falciparum</i> infection. metPFD and mxtPFD, the mean and maximum <i>P. falciparum</i> parasite densities during asymptomatic infection. Vertical dotted lines represent chromosome boundaries, horizontal dotted lines indicate nominal <i>p</i> values corresponding to LOD score.</p
Detailed linkage analysis results with 2 methods: variance component (SOLAR and MERLIN) and regression (MERLIN); ⧫ for SOLAR variance component, âȘ for MERLIN regression, ⎠for MERLIN variance component.
<p>(A) Chromosome 5, (B) Chromosome 12, (C) Chromosome 13.</p