Inferred relatedness and heritability in malaria parasites

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

Research output: Contribution to journalArticle

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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 H(2) in 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 H(2). Inhibitory concentrations (IC(50)) for six drugs showed significant H(2) (0.24 to 0.79, p = 0.06 to 2.85 x 10(-9)), demonstrating that this study design has adequate power. However, a phenotype of current interest--parasite clearance following ACT--showed no detectable heritability (H(2) = 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 H(2) can be effectively measured in malaria parasite populations using minimal genotype data, allowing rational design of genome-wide association studies; and (ii) while drug response (IC(50)) shows significant H(2), parasite clearance following ACT was not heritable in the population studied.

Original languageEnglish (US)
Pages (from-to)2531-2540
Number of pages10
JournalProceedings. Biological sciences / The Royal Society
Volume277
Issue number1693
DOIs
StatePublished - Aug 22 2010
Externally publishedYes

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malaria
heritability
relatedness
Malaria
parasite
Parasites
parasites
artemisinin
drug
therapeutics
Population
inhibitory concentration 50
Genes
Pharmaceutical Preparations
Myanmar
drug resistance
drugs
Twin Studies
antimalarials
Genome-Wide Association Study

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Anderson, T. J. C., Williams, J. T., Nair, S., Sudimack, D., Barends, M., Jaidee, A., ... Nosten, F. (2010). Inferred relatedness and heritability in malaria parasites. Proceedings. Biological sciences / The Royal Society, 277(1693), 2531-2540. https://doi.org/10.1098/rspb.2010.0196

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

In: Proceedings. Biological sciences / The Royal Society, Vol. 277, No. 1693, 22.08.2010, p. 2531-2540.

Research output: Contribution to journalArticle

Anderson, TJC, Williams, JT, Nair, S, Sudimack, D, Barends, M, Jaidee, A, Price, RN & Nosten, F 2010, 'Inferred relatedness and heritability in malaria parasites', Proceedings. Biological sciences / The Royal Society, vol. 277, no. 1693, pp. 2531-2540. https://doi.org/10.1098/rspb.2010.0196
Anderson TJC, Williams JT, Nair S, Sudimack D, Barends M, Jaidee A et al. Inferred relatedness and heritability in malaria parasites. Proceedings. Biological sciences / The Royal Society. 2010 Aug 22;277(1693):2531-2540. https://doi.org/10.1098/rspb.2010.0196
Anderson, Tim J C ; Williams, Jeff T. ; Nair, Shalini ; Sudimack, Daniel ; Barends, Marion ; Jaidee, Anchalee ; Price, Ric N. ; Nosten, François. / Inferred relatedness and heritability in malaria parasites. In: Proceedings. Biological sciences / The Royal Society. 2010 ; Vol. 277, No. 1693. pp. 2531-2540.
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