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 journalArticlepeer-review

35 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2531-2540
Number of pages10
JournalProceedings of the Royal Society B: Biological Sciences
Volume277
Issue number1693
DOIs
StatePublished - Aug 22 2010
Externally publishedYes

Keywords

  • Artemisinin
  • Clearance rate
  • Clones
  • Drug resistance
  • Heritability
  • Twins

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Environmental Science(all)
  • Agricultural and Biological Sciences(all)

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