Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0

Genetic and molecular basis of drug resistance and species-specific drug action in Schistosome parasites


ABSTRACT: Oxamniquine resistance evolved in the human blood fluke (Schistosoma mansoni) in Brazil in the 1970s. We crossed parental parasites differing ~500-fold in drug response, determined drug sensitivity and marker segregation in clonally-derived F2s, and identified a single QTL (LOD=31) on chromosome 6. A sulfotransferase was identified as the causative gene using RNAi knockdown and biochemical complementation assays and we subsequently demonstrated independent origins of loss-of-function mutations in field-derived and laboratory-selected resistant parasites. These results demonstrate the utility of linkage mapping in a human helminth parasite, while crystallographic analyses of protein-drug interactions illuminate the mode of drug action and provide a framework for rational design of oxamniquine derivatives that kill both S. mansoni and S. haematobium, the two species responsible for >99% of schistosomiasis cases worldwide. mRNA profiles from adult worms resistant (HR, 3 replicates) and susceptible (LE, 2 replicates) to the oxamniquine drug were compared to identify differential expression in genes related to drug resistance

ORGANISM(S): Schistosoma mansoni

SUBMITTER: Timothy ANDERSON 

PROVIDER: E-GEOD-51847 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

altmetric image

Publications


Oxamniquine resistance evolved in the human blood fluke (Schistosoma mansoni) in Brazil in the 1970s. We crossed parental parasites differing ~500-fold in drug response, determined drug sensitivity and marker segregation in clonally derived second-generation progeny, and identified a single quantitative trait locus (logarithm of odds = 31) on chromosome 6. A sulfotransferase was identified as the causative gene by using RNA interference knockdown and biochemical complementation assays, and we su  ...[more]

Similar Datasets

2013-12-05 | GSE51847 | GEO
2011-05-27 | GSE29535 | GEO
2015-12-10 | E-GEOD-75861 | biostudies-arrayexpress
2015-12-10 | GSE75861 | GEO
2011-05-27 | E-GEOD-29535 | biostudies-arrayexpress
2012-04-01 | GSE33525 | GEO
2013-05-30 | GSE39732 | GEO
2011-07-30 | GSE28293 | GEO
2016-03-08 | GSE78967 | GEO
2012-03-31 | E-GEOD-33525 | biostudies-arrayexpress