Single-nucleotide polymorphism, linkage disequilibrium and geographic structure in the malaria parasite Plasmodium vivax: prospects for genome-wide association studies
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
18/04/2012
18/04/2012
2010
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Resumo |
Background: The ideal malaria parasite populations for initial mapping of genomic regions contributing to phenotypes such as drug resistance and virulence, through genome-wide association studies, are those with high genetic diversity, allowing for numerous informative markers, and rare meiotic recombination, allowing for strong linkage disequilibrium (LD) between markers and phenotype-determining loci. However, levels of genetic diversity and LD in field populations of the major human malaria parasite P. vivax remain little characterized. Results: We examined single-nucleotide polymorphisms (SNPs) and LD patterns across a 100-kb chromosome segment of P. vivax in 238 field isolates from areas of low to moderate malaria endemicity in South America and Asia, where LD tends to be more extensive than in holoendemic populations, and in two monkey-adapted strains (Salvador-I, from El Salvador, and Belem, from Brazil). We found varying levels of SNP diversity and LD across populations, with the highest diversity and strongest LD in the area of lowest malaria transmission. We found several clusters of contiguous markers with rare meiotic recombination and characterized a relatively conserved haplotype structure among populations, suggesting the existence of recombination hotspots in the genome region analyzed. Both silent and nonsynonymous SNPs revealed substantial between-population differentiation, which accounted for similar to 40% of the overall genetic diversity observed. Although parasites clustered according to their continental origin, we found evidence for substructure within the Brazilian population of P. vivax. We also explored between-population differentiation patterns revealed by loci putatively affected by natural selection and found marked geographic variation in frequencies of nucleotide substitutions at the pvmdr-1 locus, putatively associated with drug resistance. Conclusion: These findings support the feasibility of genome-wide association studies in carefully selected populations of P. vivax, using relatively low densities of markers, but underscore the risk of false positives caused by population structure at both local and regional levels. National Institutes of Health (NIH)[RO1 AI 075416-01] National Institutes of Health (NIH)[5R03TW007966-02] DFW National Institute of Allergy and Infectious Diseases (NIAID) NIH Conselho Nacional de Desenvolvimento CientIfico e Tecnologico (CNPq)[470570/2006-7] Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[05/51988-0] Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[07/51199-0] |
Identificador |
BMC GENETICS, v.11, 2010 1471-2156 http://producao.usp.br/handle/BDPI/15907 10.1186/1471-2156-11-65 |
Idioma(s) |
eng |
Publicador |
BIOMED CENTRAL LTD |
Relação |
BMC Genetics |
Direitos |
openAccess Copyright BIOMED CENTRAL LTD |
Palavras-Chave | #BRAZILIAN AMAZON REGION #CHLOROQUINE RESISTANCE #POPULATION-STRUCTURE #TRANSMISSION DYNAMICS #MOLECULAR MARKERS #NATURAL-SELECTION #ALLELIC DIVERSITY #GENETIC-STRUCTURE #HAPLOTYPE BLOCKS #RURAL AMAZONIA #Genetics & Heredity |
Tipo |
article original article publishedVersion |