TY - JOUR
T1 - Microsatellite analysis of chloroquine resistance associated alleles and neutral loci reveal genetic structure of Indian Plasmodium falciparum
AU - Mallick, Prashant K.
AU - Sutton, Patrick L.
AU - Singh, Ruchi
AU - Singh, Om P.
AU - Dash, Aditya P.
AU - Singh, Ashok K.
AU - Carlton, Jane M.
AU - Bhasin, Virendra K.
N1 - Funding Information:
PKM was supported by funds from the Council of Scientific and Industrial Research, India and grant 5D43TW007884-05 “Promotion of Plasmodium Research and Training in India” from the U.S. National Institutes of Health/Fogarty International Center and by NIMR (ICMR), New Delhi. PLS was supported by an NIH/Fogarty International Center U.S. Global Health Postdoctoral Scientist Fellowship 3D43TW007884-03S1 . A set of samples used in the study were collected during a project of therapeutic efficacy of chloroquine supported by a grant USAID SE/05/209279 . All laboratory isolates, including MRA819G, MRA820G, MRA150G, MRA155G, MRA152G, MRA818G, MRA398, MRA102G, were kindly provided by the Malaria Reagent and Reference Resource Center (MR4). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Fogarty International Center or the National Institutes of Health or NIMR. We sincerely thank all the staff members of NIMR, Delhi and the respective field units, for their help, cooperation and support during the study. This research article bears the NIMR publication committee approval number 028/2012.
PY - 2013/10
Y1 - 2013/10
N2 - Efforts to control malignant malaria caused by Plasmodium falciparum are hampered by the parasite's acquisition of resistance to antimalarial drugs, e.g., chloroquine. This necessitates evaluating the spread of chloroquine resistance in any malaria-endemic area. India displays highly variable malaria epidemiology and also shares porous international borders with malaria-endemic Southeast Asian countries having multi-drug resistant malaria. Malaria epidemiology in India is believed to be affected by two major factors: high genetic diversity and evolving drug resistance in P. falciparum. How transmission intensity of malaria can influence the genetic structure of chloroquine-resistant P. falciparum population in India is unknown. Here, genetic diversity within and among P. falciparum populations is analyzed with respect to their prevalence and chloroquine resistance observed in 13 different locations in India. Microsatellites developed for P. falciparum, including three putatively neutral and seven microsatellites thought to be under a hitchhiking effect due to chloroquine selection were used. Genetic hitchhiking is observed in five of seven microsatellites flanking the gene responsible for chloroquine resistance. Genetic admixture analysis and F-statistics detected genetically distinct groups in accordance with transmission intensity of different locations and the probable use of chloroquine. A large genetic break between the chloroquine-resistant parasite of the Northeast-East-Island group and Southwest group (FST= 0.253, P< 0.001) suggests a long period of isolation or a possibility of different origin between them. A pattern of significant isolation by distance was observed in low transmission areas (r= 0.49, P= 0.003, N=83, Mantel test). An unanticipated pattern of spread of hitchhiking suggests genetic structure for Indian P. falciparum population. Overall, the study suggests that transmission intensity can be an efficient driver for genetic differentiation at both neutral and adaptive loci across India.
AB - Efforts to control malignant malaria caused by Plasmodium falciparum are hampered by the parasite's acquisition of resistance to antimalarial drugs, e.g., chloroquine. This necessitates evaluating the spread of chloroquine resistance in any malaria-endemic area. India displays highly variable malaria epidemiology and also shares porous international borders with malaria-endemic Southeast Asian countries having multi-drug resistant malaria. Malaria epidemiology in India is believed to be affected by two major factors: high genetic diversity and evolving drug resistance in P. falciparum. How transmission intensity of malaria can influence the genetic structure of chloroquine-resistant P. falciparum population in India is unknown. Here, genetic diversity within and among P. falciparum populations is analyzed with respect to their prevalence and chloroquine resistance observed in 13 different locations in India. Microsatellites developed for P. falciparum, including three putatively neutral and seven microsatellites thought to be under a hitchhiking effect due to chloroquine selection were used. Genetic hitchhiking is observed in five of seven microsatellites flanking the gene responsible for chloroquine resistance. Genetic admixture analysis and F-statistics detected genetically distinct groups in accordance with transmission intensity of different locations and the probable use of chloroquine. A large genetic break between the chloroquine-resistant parasite of the Northeast-East-Island group and Southwest group (FST= 0.253, P< 0.001) suggests a long period of isolation or a possibility of different origin between them. A pattern of significant isolation by distance was observed in low transmission areas (r= 0.49, P= 0.003, N=83, Mantel test). An unanticipated pattern of spread of hitchhiking suggests genetic structure for Indian P. falciparum population. Overall, the study suggests that transmission intensity can be an efficient driver for genetic differentiation at both neutral and adaptive loci across India.
KW - Chloroquine resistance
KW - Gene-flow
KW - Hitchhiking
KW - India
KW - Plasmodium falciparum
KW - Transmission area
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U2 - 10.1016/j.meegid.2013.07.009
DO - 10.1016/j.meegid.2013.07.009
M3 - Article
C2 - 23871774
AN - SCOPUS:84881234087
SN - 1567-1348
VL - 19
SP - 164
EP - 175
JO - Infection, Genetics and Evolution
JF - Infection, Genetics and Evolution
ER -