GEPHE SUMMARY
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Gephebase Gene
Entry Status
Published
GepheID
GP00001470
Main curator
Prigent
PHENOTYPIC CHANGE
Trait Category
Trait State in Taxon A
Human blood fluke OXA-sensitive (wild-type)
Trait State in Taxon B
Human blood fluke laboratory-selected OXA-resistant (500-fold reduction in drug sensitivity)
Ancestral State
Taxon A
Taxonomic Status
Taxon A
Latin Name
Common Name
-
Synonyms
-
Rank
species
Lineage
cellular organisms; Eukaryota; Opisthokonta; Metazoa; Eumetazoa; Bilateria; Platyhelminthes; Trematoda; Digenea; Strigeidida; Schistosomatoidea; Schistosomatidae; Schistosoma
NCBI Taxonomy ID
is Taxon A an Infraspecies?
No
Taxon B
Latin Name
Common Name
-
Synonyms
-
Rank
species
Lineage
cellular organisms; Eukaryota; Opisthokonta; Metazoa; Eumetazoa; Bilateria; Platyhelminthes; Trematoda; Digenea; Strigeidida; Schistosomatoidea; Schistosomatidae; Schistosoma
NCBI Taxonomy ID
is Taxon B an Infraspecies?
No
GENOTYPIC CHANGE
Generic Gene Name
SULT-OR
Synonyms
Smp_089320
String
-
Sequence Similarities
-
GO - Molecular Function
GO - Biological Process
-
GO - Cellular Component
-
Presumptive Null
Molecular Type
Aberration Type
Deletion Size
1-9 bp
Molecular Details of the Mutation
E142del
Experimental Evidence
Main Reference
Authors
Valentim CL; Cioli D; Chevalier FD; Cao X; Taylor AB; Holloway SP; Pica-Mattoccia L; Guidi A; et al.
... show more
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 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 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.
Additional References
RELATED GEPHE
Related Genes
No matches found.
Related Haplotypes
EXTERNAL LINKS
COMMENTS
identified as the causative gene using RNAi knockdown and biochemical complementation assays
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