Differential genetic hitchhiking around mutant pfcrt alleles in the Indian Plasmodium falciparum population

Abstract

With regard to chloroquine there is regional variation in the selection pressure on the P. falciparum population in India. These findings will help the regional implementation of drug policy in India's malaria control programme.

Microsatellite analysis of chloroquine resistance associated alleles and neutral loci reveal genetic structure of Indian Plasmodium falciparum

“…The difference in relative fitness of pfcrt -haplotypes within different epidemiological conditions at the time of sampling may have contributed to this differential pattern of selective sweep. However, the data presented here concurs with a recent report explained molecular basis of CQR differs with changing transmission intensities in India (Lumb et al, 2012). Hence, a different pattern of genotypes had developed in various regions (broadly HTA and LTA), which translated into the detection of geographical structure among CQ-resistant Indian P. falciparum .…”

“…This in turn reflects the earlier observation of varied level of selective sweep associated with regional variation in chloroquine pressure (Lumb et al, 2012). The pairwise F ST estimate at pfcrt -flanking loci show high genetic differentiation between East-Island (ORS, JHK, CHG, CN) and Northwest (UP, RAJ, GUJ), strong differentiation between East-Island and Southwest (GOA&TN), indicating a limited migration of resistant haplotypes between East-Island with that of Northwest and Southwest.…”

“…Studies on chloroquine resistance (CQR) found that: (i) multiple foci exist for the origin of CQR, one in Asia spreading to Africa, two in South America, one in Papua New Guinea (PNG) and one in the Philippines; (ii) Southeast Asia and Africa share the resistant CVIET haplotype (amino acids at codon 72 to 76) in the Plasmodium falciparum chloroquine resistance transporter ( pfcrt ) gene, suggesting the role of human migration in conjunction with the spread of chloroquine-resistant parasites (Wootton et al, 2002); and (iii) resistant SVMNT haplotype characterizes the South American type, which is prevalent throughout South America and the Pacific region (Mehlotra et al, 2005). Studies evaluating genetic variation within microsatellite loci flanking the pfcrt gene reported invasion of the PNG type SVMNT throughout India (Lumb et al, 2012; Mixson-Hayden et al, 2010). Invasion of the same resistant SVMNT into Pakistan has also been reported (Rawasia et al, 2012).…”

A call to arms: on refining Plasmodium vivax microsatellite marker panels for comparing global diversity

“…For example, recent studies in P. falciparum have indicated that H e in MS is inversely correlated with the proximity of the MS locus to the P. falciparum chloroquine resistance transporter gene, which is known to be associated with chloroquine resistance in this parasite [50-53]. This relationship is likely a result of genetic hitchhiking, but is still important to consider when selecting MS loci to describe genetic diversity in a population as it may impact the polymorphic potential.…”

Genetics of chloroquine-resistant malaria: a haplotypic view

“…In Indonesia, apart from the highly frequent SVMNT haplotype, a new haplotype, CVMNN, was found to be frequent in Lombok and Irian Jaya ( Huaman et al 2004 ). Most interestingly, India has a mixture of many CQR- Pfcrt haplotypes, which are primarily dominated by SVMNT, but also show appreciable frequencies of CVIET, CVMNT and CVIDT ( Vinayak et al 2003 , 2006 , Vathsala et al 2004 , Mittra et al 2006 , Keen et al 2007 Pati et al 2007 , Bharti et al 2009 , Mixon-Hayden et al 2010 , Awasthi et al 2011 , Sutar et al 2011 , Lumb et al 2012 ). In Pakistan, Iran and Sri Lanka, the S agt VMNT haplotype is reported at appreciable frequencies and is believed to have been imported from India ( Zakeri et al 2008 , Zhang et al 2011 , Rawasia et al.…”