An Analysis of Genetic Diversity and Inbreeding in Wuchereria bancrofti Implications for the Spread and Detection of Drug Resistance 英文参考文献.docVIP

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An Analysis of Genetic Diversity and Inbreeding in Wuchereria bancrofti Implications for the Spread and Detection of Drug Resistance 英文参考文献.doc

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An Analysis of Genetic Diversity and Inbreeding in Wuchereria bancrofti Implications for the Spread and Detection of Drug Resistance 英文参考文献

AnAnalysisofGeneticDiversityandInbreedingin Wuchereriabancrofti:ImplicationsfortheSpreadand DetectionofDrugResistance ThomasS.Churcher1*,AnneE.Schwab2,RogerK.Prichard2,Mar?′a-GloriaBasa′n?ez1 1DepartmentofInfectiousDiseaseEpidemiology,St.Mary’sCampus,ImperialCollegeLondon,London,UnitedKingdom,2InstituteofParasitology,McGillUniversity, Sainte-Anne-de-Bellevue,Quebec,Canada Abstract Estimates of genetic diversity in helminth infections of humans often have to rely on genotyping (immature) parasite transmission stages instead of adult worms. Here we analyse the results of one such study investigating a single polymorphic locus (a change at position 200 of the b-tubulin gene) in microfilariae of the lymphatic filarial parasite Wuchereria bancrofti. The presence of this genetic change has been implicated in benzimidazole resistance in parasitic nematodesoffarmedruminants.MicrofilariaewereobtainedfrompatientsofthreeWestAfricanvillages,twoofwhichwere sampled prior to the introduction of mass drug administration. An individual-based stochastic model was developed showing that a wide range of allele frequencies in the adult worm populations could have generated the observed microfilarial genetic diversity. This suggests that appropriate theoretical null models are required in order to interpret studiesthatgenotypetransmissionstages.Wright’shierarchicalF-statisticwasusedtoinvestigatethepopulationstructure in W. bancrofti microfilariae and showed significant deficiency of heterozygotes compared to the Hardy-Weinberg equilibrium;thismaybepartiallycausedbyahighdegreeofparasitegeneticdifferentiationbetweenhosts.Studiesseeking toquantifyaccuratelythegeneticdiversityofhelminthpopulationsbyanalysingtransmissionstagesshouldincreasetheir sample size to account for the variability in allele frequency between different parasite life-stages. Helminth genetic differentiationbetweenhostsandnon-randommatingwillalsoincreasethenumberofhosts(andthenumberofsamples perhost)thatneedtobegenotype