Inferred relatedness and heritability in malaria parasites

Tim Anderson, Jeff T Williams, Shalini Nair, Daniel Sudimack, Marion Barends, Anchalee Jaidee, Ric Price, François Nosten

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Malaria parasites vary in phenotypic traits of biomedical or biological interest such as growth rate, virulence, sex ratio and drug resistance, and there is considerable interest in identifying the genes that underlie this variation. An important first step is to determine trait heritability (H 2). We evaluate two approaches to measuring H2in natural parasite populations using relatedness inferred from genetic marker data. We collected single-clone Plasmodium falciparum infections from 185 patients from the Thailand-Burma border, monitored parasite clearance following treatment with artemisinin combination therapy (ACT), measured resistance to six antimalarial drugs and genotyped parasites using 335 microsatellites. We found strong relatedness structure. There were 27 groups of two to eight clonally identical (CI) parasites, and 74 per cent of parasites showed significant relatedness to one or more other parasites. Initially, we used matrices of allele sharing and variance components (VC) methods to estimate H2. Inhibitory concentrations (IC2) for six drugs showed significant H 2(0.24 to 0.79, p = 0.06 to 2.85 �10-9), demonstrating that this study design has adequate power. However, a phenotype of current interest-parasite clearance following ACT-showed no detectable heritability (H2= 0-0.09, ns) in this population. The existence of CI parasites allows the use of a simple ANOVA approach for quantifying H 2, analogous to that used in human twin studies. This gave similar results to the VC method and requires considerably less genotyping information. We conclude (i) that H2can be effectively measured in malaria parasite populations using minimal genotype data, allowing rational design of genome-wide association studies; and (ii) while drug response (IC50) shows significant H2, parasite clearance following ACT was not heritable in the population studied. � 2010 The Royal Society.
    Original languageEnglish
    Pages (from-to)2531-2540
    Number of pages10
    JournalProceedings of the Royal Society B: Biological Sciences
    Volume277
    Issue number1693
    Publication statusPublished - 2010

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    malaria
    heritability
    relatedness
    Malaria
    parasite
    Parasites
    parasites
    artemisinin
    drug
    therapeutics
    Population
    Genes
    Pharmaceutical Preparations
    Myanmar
    drug resistance
    drugs
    Twin Studies
    antimalarials
    Genome-Wide Association Study
    Sex Ratio

    Cite this

    Anderson, T., Williams, J. T., Nair, S., Sudimack, D., Barends, M., Jaidee, A., ... Nosten, F. (2010). Inferred relatedness and heritability in malaria parasites. Proceedings of the Royal Society B: Biological Sciences, 277(1693), 2531-2540.
    Anderson, Tim ; Williams, Jeff T ; Nair, Shalini ; Sudimack, Daniel ; Barends, Marion ; Jaidee, Anchalee ; Price, Ric ; Nosten, François. / Inferred relatedness and heritability in malaria parasites. In: Proceedings of the Royal Society B: Biological Sciences. 2010 ; Vol. 277, No. 1693. pp. 2531-2540.
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    Anderson, T, Williams, JT, Nair, S, Sudimack, D, Barends, M, Jaidee, A, Price, R & Nosten, F 2010, 'Inferred relatedness and heritability in malaria parasites', Proceedings of the Royal Society B: Biological Sciences, vol. 277, no. 1693, pp. 2531-2540.

    Inferred relatedness and heritability in malaria parasites. / Anderson, Tim; Williams, Jeff T; Nair, Shalini; Sudimack, Daniel; Barends, Marion; Jaidee, Anchalee; Price, Ric; Nosten, François.

    In: Proceedings of the Royal Society B: Biological Sciences, Vol. 277, No. 1693, 2010, p. 2531-2540.

    Research output: Contribution to journalArticleResearchpeer-review

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    AU - Anderson, Tim

    AU - Williams, Jeff T

    AU - Nair, Shalini

    AU - Sudimack, Daniel

    AU - Barends, Marion

    AU - Jaidee, Anchalee

    AU - Price, Ric

    AU - Nosten, François

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    AB - Malaria parasites vary in phenotypic traits of biomedical or biological interest such as growth rate, virulence, sex ratio and drug resistance, and there is considerable interest in identifying the genes that underlie this variation. An important first step is to determine trait heritability (H 2). We evaluate two approaches to measuring H2in natural parasite populations using relatedness inferred from genetic marker data. We collected single-clone Plasmodium falciparum infections from 185 patients from the Thailand-Burma border, monitored parasite clearance following treatment with artemisinin combination therapy (ACT), measured resistance to six antimalarial drugs and genotyped parasites using 335 microsatellites. We found strong relatedness structure. There were 27 groups of two to eight clonally identical (CI) parasites, and 74 per cent of parasites showed significant relatedness to one or more other parasites. Initially, we used matrices of allele sharing and variance components (VC) methods to estimate H2. Inhibitory concentrations (IC2) for six drugs showed significant H 2(0.24 to 0.79, p = 0.06 to 2.85 �10-9), demonstrating that this study design has adequate power. However, a phenotype of current interest-parasite clearance following ACT-showed no detectable heritability (H2= 0-0.09, ns) in this population. The existence of CI parasites allows the use of a simple ANOVA approach for quantifying H 2, analogous to that used in human twin studies. This gave similar results to the VC method and requires considerably less genotyping information. We conclude (i) that H2can be effectively measured in malaria parasite populations using minimal genotype data, allowing rational design of genome-wide association studies; and (ii) while drug response (IC50) shows significant H2, parasite clearance following ACT was not heritable in the population studied. � 2010 The Royal Society.

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    Anderson T, Williams JT, Nair S, Sudimack D, Barends M, Jaidee A et al. Inferred relatedness and heritability in malaria parasites. Proceedings of the Royal Society B: Biological Sciences. 2010;277(1693):2531-2540.