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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2010.tde-18102010-103122
Document
Author
Full name
Pamela Orjuela Sanchez
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2010
Supervisor
Committee
Ferreira, Marcelo Urbano (President)
Briones, Marcelo Ribeiro da Silva
Brito, Cristiana Ferreira Alves de
Lacerda, Marcus Vinicius Guimarães de
Wunderlich, Gerhard
Title in Portuguese
Diversidade genética em populações de Plasmodium vivax: análise de marcadores genéticos neutros e de genes potencialmente associados à resistência a drogas.
Keywords in Portuguese
Malária
Marcador molecular
Recombinação genética
Resistência
Variação genética
Abstract in Portuguese
Através da análise de microssatélites e SNPs, incluindo tanto marcadores neutros como sujeitos a seleção, neste trabalho se demonstrou que: 1) As populações brasileiras de P. vivax (Pv) são mais diversas que as populações simpátricas de P. falciparum (Pf), porém ambas apresentam desequilíbrio de ligação. 2) Os polimorfismos neutros apresentam alta variabilidade ao longo do tempo em ambas as espécies, em contraste com a estabilidade observada nos marcadores sob seleção. 3) As altas taxas de recorrências por Pv na Amazônia brasileira são causadas, em sua maioria, por parasitas geneticamente não relacionados. 4) A recombinação não meiótica contribui substancialmente à diversidade dos domínios repetitivos de PvCSP. 5) Os SNPs nos genes pvmdr1 e pvcrt-o de isolados de Pv resistentes à cloroquina não se associam ao seu fenótipo in vivo. Finalmente, através da genotipagem de 57 SNPs do cromossomo 8 de Pv em 234 isolados do Brasil e da Ásia observou-se que, em Pv, a diversidade e a recombinação mitótica não se associam aos níveis de endemicidade como acontece em Pf e que Pv apresenta estrutura populacional continental e subcontinental no Brasil.
Title in English
Genetic diversity of Plasmodium vivax populations: analysis of neutral genetic markers and genes potentially associated with drug resistance.
Keywords in English
Genetic recombination
Genetic variation
Malaria
Molecular marker
Resistance
Abstract in English
Through the analysis of microsatellites and SNPs, including both neutral and under selection markers, this work showed that: 1) The Brazilian populations of P. vivax (Pv) are more diverse than sympatric P. falciparum (Pf) populations, but both exhibit linkage disequilibrium. 2) For both species, neutral polymorphisms showed high variability over time, contrasting with the stability of under markers under selection. 3) The high rate of Pv recurrences in the Brazilian Amazon region is mostly due to genetically unrelated parasites. 4) Non-meiotic recombination substantially contributes to PvCSP repetitive domain diversity. 5) SNPs at pvmdr1 and pvcrt-o genes of chloroquine resistant isolates of Pv are not associated with the in vivo phenotype. Finally, 57 SNP genotyping of chromosome 8 of Pv among 234 isolates from Brazil and Asia showed that, in Pv, diversity and mitotic recombination are not associated with levels of endemicity as in Pf and that Pv presents continental population structure and subcontinental structure in Brazil.
 
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Publishing Date
2010-11-05
 
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