Inferred relatedness and heritability in malaria parasites.
Inferred relatedness and heritability in malaria parasites.
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DOI：
10.1098/rspb.2010.0196
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发表时间：
2010-08-22
期刊：
影响因子：
--
通讯作者：
Nosten F
中科院分区：
文献类型：
--
作者：
Anderson TJ;Williams JT;Nair S;Sudimack D;Barends M;Jaidee A;Price RN;Nosten F
疟疾寄生虫在生物医学或生物学意义上的表型性状，如生长率、毒力、性别比和耐药性方面各不相同，人们对鉴定这种变异的基因非常感兴趣。重要的第一步是确定性状遗传力（H2）。我们评估两种方法来测量H2在自然寄生虫种群使用遗传标记数据推断的相关性。我们收集了来自泰缅边境的185名患者的单克隆恶性疟原虫感染，监测了青蒿素联合疗法（ACT）治疗后的寄生虫清除情况，测量了对6种抗疟药物的耐药性，并使用335个微卫星对寄生虫进行了基因分型。我们发现了强关联结构。有27组2至8个克隆相同（CI）的寄生虫，74%的寄生虫显示出显着的关系，一个或多个其他寄生虫。最初，我们使用等位基因共享矩阵和方差分量（VC）方法来估计H2。6种药物的抑制浓度（IC 50）显示出显著的H2（0.24至0.79，p = 0.06至2.85 × 10−9），表明该研究设计具有足够的把握度。然而，目前的利益寄生虫清除表型ACT后，没有显示出可检测的遗传力（H2 = 0-0.09，ns），在这个群体。Cl寄生虫的存在允许使用简单的ANOVA方法来定量H2，类似于人类双胞胎研究中使用的方法。这给出了与VC方法相似的结果，并且需要相当少的基因分型信息。我们的结论是：（i）H2可以有效地测量疟疾寄生虫种群使用最少的基因型数据，允许全基因组关联研究的合理设计;（ii）虽然药物反应（IC 50）显示显着的H2，寄生虫清除后ACT是不遗传的人口研究。
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 (H2). We evaluate two approaches to measuring H2 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 H2. Inhibitory concentrations (IC50) for six drugs showed significant H2 (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 H2, 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 H2 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 (IC50) shows significant H2, parasite clearance following ACT was not heritable in the population studied.
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影响因子：
3.7
作者：
Carrara, Verena Ilona;Zwang, Julien;Ashley, Elizabeth A.;Price, Ric N.;Stepniewska, Kasia;Barends, Marion;Brockman, Alan;Anderson, Tim;McGready, Rose;Phaiphun, Lucy;Proux, Stephane;van Vugt, Michele;Hutagalung, Robert;Lwin, Khin Maung;Phyo, Aung Pyae;Preechapornkul, Piyanuch;Imwong, Mallika;Pukrittayakamee, Sasithon;Singhasivanon, Pratap;White, Nicholas J.;Nosten, Francois
通讯作者：
Nosten, Francois
影响因子：
30.8
作者：
Goering, Harald H. H.;Curran, Joanne E.;Blangero, John
通讯作者：
Blangero, John
影响因子：
4.9
作者：
Fernández, J;Toro, MA
通讯作者：
Toro, MA
DOI：
10.1016/0035-9203(91)90217-m
发表时间：
1991-07-01
影响因子：
2.2
作者：
CONWAY, DJ;MCBRIDE, JS
通讯作者：
MCBRIDE, JS
DOI：
10.4269/ajtmh.2009.09-0406
发表时间：
2009-12
期刊：
The American journal of tropical medicine and hygiene
影响因子：
--
作者：
Doumbo OK;Thera MA;Koné AK;Raza A;Tempest LJ;Lyke KE;Plowe CV;Rowe JA
通讯作者：
Rowe JA