Measuring_mutation_in_Plasmodium_falciparum_clone_trees-sc-2159
Measuring_mutation_in_Plasmodium_falciparum_clone_trees
Mutation arising during DNA replication is a potential source of antimalarial drug resistance in Plasmodium falciparum. This study compares next generation whole genome sequence data between clonal generations of serially diluted, culture-adapted P. falciparum, so that novel mutations arising during in vitro cell division can be detected longitudinally. This provides an indication firstly of the mutation rate for different P. falciparum strains, secondly of the types of mutation that the P. falciparum genome is prone to, and thirdly where in the genome mutations tend to arise. Strains under analysis include Dd2, 3D7, W2 and genetically modified 3D7 that has undergone allele exchange or knockout in genes relevant to DNA synthesis and repair (the major determinants of mutation rate). Variation in mutability between strains could be partially responsible for the observed differences in the capacity of P. falciparum strains to acquire drug resistance to novel antimalarial compounds. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
Cultured strains of P. falciparum are serially diluted and then clonally expanded to allow next generation sequencing. Rare mutations that have arisen during cell division are thus amplified in the population through clonal dilution, allowing the asexual mutation rate to be estimated.