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Inferred relatedness and heritability in malaria parasites

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))....

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Autores principales: Anderson, Tim J. C., Williams, Jeff T., Nair, Shalini, Sudimack, Daniel, Barends, Marion, Jaidee, Anchalee, Price, Ric N., Nosten, François
Formato: Texto
Lenguaje:English
Publicado: The Royal Society 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894920/
https://www.ncbi.nlm.nih.gov/pubmed/20392725
http://dx.doi.org/10.1098/rspb.2010.0196
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author Anderson, Tim J. C.
Williams, Jeff T.
Nair, Shalini
Sudimack, Daniel
Barends, Marion
Jaidee, Anchalee
Price, Ric N.
Nosten, François
author_facet Anderson, Tim J. C.
Williams, Jeff T.
Nair, Shalini
Sudimack, Daniel
Barends, Marion
Jaidee, Anchalee
Price, Ric N.
Nosten, François
author_sort Anderson, Tim J. C.
collection PubMed
description 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 × 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.
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spelling pubmed-28949202010-07-02 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 Proc Biol Sci Research articles 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 × 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. The Royal Society 2010-08-22 2010-04-14 /pmc/articles/PMC2894920/ /pubmed/20392725 http://dx.doi.org/10.1098/rspb.2010.0196 Text en © 2010 The Royal Society http://creativecommons.org/licenses/by/2.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research articles
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
title Inferred relatedness and heritability in malaria parasites
title_full Inferred relatedness and heritability in malaria parasites
title_fullStr Inferred relatedness and heritability in malaria parasites
title_full_unstemmed Inferred relatedness and heritability in malaria parasites
title_short Inferred relatedness and heritability in malaria parasites
title_sort inferred relatedness and heritability in malaria parasites
topic Research articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894920/
https://www.ncbi.nlm.nih.gov/pubmed/20392725
http://dx.doi.org/10.1098/rspb.2010.0196
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