Characteristic of genetic hitchhiking around Plasmodium falciparum dihydrofolate reductase (dhfr) gene associated with pyrimethamine resistance, in India. - Related Articles
Characteristic of genetic hitchhiking around Plasmodium falciparum dihydrofolate reductase (dhfr) gene associated with pyrimethamine resistance, in India.
Antimicrob Agents Chemother. 2009 Sep 28;
Authors: Lumb V, Das MK, Singh N, Dev V, Khan W, Sharma YD
Sulfadoxine-Pyrimethamine (SP) resistance in Plasmodium falciparum has been widespread among the continents and causing the major hurdle in controlling malaria. Resistance is mainly encoded by point mutations in P.falciparum target genes dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps). To study the origin and evolution of pyrimethamine resistance in Indian subcontinent, microsatellite markers flanking pfdhfr gene were mapped. Here, we describe characteristic of genetic hitchhiking around pfdhfr gene among 190 P.falciparum isolates. These isolates were collected from five different geographical regions of India (Uttar Pradesh, Madhya Pradesh, Assam, Orissa, and Andaman and Nicobar Islands) where malarial transmission rates and level of drug resistance vary from each other. Among the isolates, we observed a significant reduction in genetic variation in the +/- 20 kb vicinity of the mutant pfdhfr alleles due to hitchhiking. This reduction in genetic diversity was more prominent around quadruple pfdhfr alleles (He = 0.23) as compared to double (He = 0.365) and single (He= 0.465) mutant alleles. Asymmetry in selective sweep flanking the pfdhfr alleles was observed among regional isolates emphasizing the drug usage in the parasite population. All the pfdhfr alleles share single microsatellite haplotype and seem to have been originated from single progenitor similar to Southeast Asian (Thailand) pfdhfr mutants. Results of the present study also indicate that the emergence of drug resistant alleles in India is a recent phenomenon as compared to other Southeast Asian countries.
PMID: 19786603 [PubMed - as supplied by publisher] [PubMed-Malaria]