title: Microsatellite analysis of chloroquine resistance associated alleles and neutral loci reveal genetic structure of Indian Plasmodium falciparum.
abstract: 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.
authors.affiliation: National Institute of Malaria Research, Indian Council of Medical Research, Dwarka Sector-8, New Delhi 110077, India.
authors.forename: Prashant K
authors.initials: PK
authors.lastname: Mallick
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Sutton
authors.forename: Ruchi
authors.initials: R
authors.lastname: Singh
authors.forename: Om P
authors.initials: OP
authors.lastname: Singh
authors.forename: Aditya P
authors.initials: AP
authors.lastname: Dash
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Singh
authors.forename: Jane M
authors.initials: JM
authors.lastname: Carlton
authors.forename: Virendra K
authors.initials: VK
authors.lastname: Bhasin
mesh_terms: D000483:Alleles; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D016054:DNA, Protozoan / Q000032:analysis / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D017125:Genes, Protozoan / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007194:India / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology* / Q000635:transmission; D018895:Microsatellite Repeats / Q000235:genetics*; D058974:Phylogeography; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan; D002738:Chloroquine
keywords: Chloroquine resistance; Gene-flow; Hitchhiking; India; Plasmodium falciparum; Transmission area