TY - JOUR
T1 - Contrasting genetic structure in Plasmodium vivax populations from Asia and South America
AU - Imwong, Mallika
AU - Nair, Shalini
AU - Pukrittayakamee, Sasithon
AU - Sudimack, Daniel
AU - Williams, Jeff T.
AU - Mayxay, Mayfong
AU - Newton, Paul N.
AU - Kim, Jung Ryong
AU - Nandy, Amitab
AU - Osorio, Lyda
AU - Carlton, Jane M.
AU - White, Nicholas J.
AU - Day, Nicholas P.J.
AU - Anderson, Tim J.C.
N1 - Funding Information:
TJCA, SN, DS, and JTW are funded by NIH RO1 AI48071. This investigation was conducted in facilities constructed with support from the Research Facilities Improvement Program Grant No. C06 RR013556 from the National Center for research Resources, National Institutes of Health. Preliminary sequence data from which microsatellite primers were designed was obtained from TIGR ( http://www.tigr.org ). Funding for the P. vivax sequencing project came from NIAID, the US Department of Defense and the Burroughs Wellcome Fund. This study was part of the Wellcome Trust-Mahidol University Oxford Tropical Medicine Research Programme, funded by the Wellcome Trust of Great Britain. MI is a Wellcome Trust training fellow (Grant 066439/Z/01/2). We thank Drs Samlane Phompida, Rattanaxay Phetsouvanh, Tiengkham Pongvongsa, Maniphone Khanthavong, Vonthalom Thongpraseth, Siamphai Keola, Ms. Manisack Phommasansack, Mr. Kai-Amphone Phonekeopaseth, Chanthala Vilaihong and Mr. Bounpon Phimphalat in Laos and the staff at CIDEIM in Colombia for assistance with collections.
PY - 2007/7
Y1 - 2007/7
N2 - Populations of Plasmodium falciparum show striking differences in linkage disequilibrium, population differentiation and diversity, but only fragmentary data exists on the genetic structure of Plasmodium vivax. We genotyped nine tandem repeat loci bearing 2-8 bp motifs from 345 P. vivax infections collected from three Asian countries and from five locations in Colombia. We observed 9-37 alleles per locus and high diversity (He = 0.72-0.79, mean = 0.75) in all countries. Numbers of multiple clone infections varied considerably: these were rare in Colombia and India, but > 60% of isolates carried multiple alleles in at least one locus in Thailand and Laos. However, only one or two of the nine loci show >1 allele in many samples, suggesting that mutation within infections may result in overestimation of true multiple carriage rates. Identical nine-locus genotypes were frequently found in Colombian populations, contributing to strong linkage disequilibrium. These identical genotypes were strongly clustered in time, consistent with epidemic transmission of clones and subsequent breakdown of allelic associations, suggesting high rates of inbreeding and low effective recombination rates in this country. In contrast, identical genotypes were rare and loci were randomly associated in all three Asian populations, consistent with higher rates of outcrossing and recombination. We observed low but significant differentiation between different Asian countries (standardized FST = 0.13-0.45). In comparison, we see greater differentiation between collection locations within Colombia (standardized FST = 0.4-0.7), and strong differentiation between continents (standardized FST = 0.48-0.79). The observed heterogeneity in multiple clone carriage rates, linkage disequilibrium and population differentiation are similar in some, but not all, respects to those observed in P. falciparum, and have important implications for the design of association mapping studies, and interpretation of P. vivax epidemiology.
AB - Populations of Plasmodium falciparum show striking differences in linkage disequilibrium, population differentiation and diversity, but only fragmentary data exists on the genetic structure of Plasmodium vivax. We genotyped nine tandem repeat loci bearing 2-8 bp motifs from 345 P. vivax infections collected from three Asian countries and from five locations in Colombia. We observed 9-37 alleles per locus and high diversity (He = 0.72-0.79, mean = 0.75) in all countries. Numbers of multiple clone infections varied considerably: these were rare in Colombia and India, but > 60% of isolates carried multiple alleles in at least one locus in Thailand and Laos. However, only one or two of the nine loci show >1 allele in many samples, suggesting that mutation within infections may result in overestimation of true multiple carriage rates. Identical nine-locus genotypes were frequently found in Colombian populations, contributing to strong linkage disequilibrium. These identical genotypes were strongly clustered in time, consistent with epidemic transmission of clones and subsequent breakdown of allelic associations, suggesting high rates of inbreeding and low effective recombination rates in this country. In contrast, identical genotypes were rare and loci were randomly associated in all three Asian populations, consistent with higher rates of outcrossing and recombination. We observed low but significant differentiation between different Asian countries (standardized FST = 0.13-0.45). In comparison, we see greater differentiation between collection locations within Colombia (standardized FST = 0.4-0.7), and strong differentiation between continents (standardized FST = 0.48-0.79). The observed heterogeneity in multiple clone carriage rates, linkage disequilibrium and population differentiation are similar in some, but not all, respects to those observed in P. falciparum, and have important implications for the design of association mapping studies, and interpretation of P. vivax epidemiology.
KW - Association mapping
KW - Heterozygosity
KW - Inbreeding
KW - Linkage disequilibrium
KW - Microsatellite
KW - Recombination
KW - Relapse
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U2 - 10.1016/j.ijpara.2007.02.010
DO - 10.1016/j.ijpara.2007.02.010
M3 - Article
C2 - 17442318
AN - SCOPUS:34249997585
VL - 37
SP - 1013
EP - 1022
JO - International Journal for Parasitology
JF - International Journal for Parasitology
SN - 0020-7519
IS - 8-9
ER -