Document Detail


Characterization of a half-size ATP-binding cassette transporter gene which may be a useful marker for ivermectin selection in Onchocerca volvulus.
MedLine Citation:
PMID:  16257066     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
ATP-binding cassette (ABC) transporters comprise a large paralogous protein family and several confer drug resistance. Ivermectin (IVM) is the only drug approved for treatment of onchocerciasis and is a substrate for some ABC transporters. Furthermore, there is accumulating evidence that IVM selects on some ABC transporter genes in Onchocerca volvulus and other parasitic nematodes. The onchocerciasis control programs rely on community based treatment with IVM each year to reduce morbidity and decrease parasite transmission. This appears to be imposing selection pressure on O. volvulus. A half-size ABC transporter cDNA has previously been reported for O. volvulus, however, the full length gene has not been previously characterized and investigated for possible selection by IVM. Genes under selection may be identified by patterns of linkage disequilibrium (LD) and a loss of genetic polymorphism at physically linked loci. Twelve genetic markers spanning the full gene were examined in O. volvulus from non-treated and IVM treated populations in Ghana. Analysis of the genomic organization of the half-size ABC transporter (OvPLP) indicates that it spans approximately 3.8 kb comprising nine exons. Worms from treated people showed a reduction in gene diversity, a loss of genetic polymorphism at several markers, a selection for specific alleles, and a reduction in the number of regions in LD; these effects were more pronounced as treatment increased. These changes suggest that IVM is imposing selection pressure on this gene. The region between transmembrane domains four and five may be a useful marker for IVM selection in O. volvulus.
Authors:
Bernadette F Ardelli; Sean B Guerriero; Roger K Prichard
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-10-06
Journal Detail:
Title:  Molecular and biochemical parasitology     Volume:  145     ISSN:  0166-6851     ISO Abbreviation:  Mol. Biochem. Parasitol.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2005-12-02     Completed Date:  2006-03-22     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8006324     Medline TA:  Mol Biochem Parasitol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  94-100     Citation Subset:  IM    
Affiliation:
Institute of Parasitology, Macdonald Campus, McGill University, Anne de Bellevue, Que., Canada H9X 3V9.
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / chemistry,  genetics*
Animals
Antiparasitic Agents / pharmacology*,  therapeutic use
Base Sequence
Exons
Female
Genetic Variation
Helminth Proteins / chemistry,  genetics
Humans
Introns
Ivermectin / pharmacology*,  therapeutic use
Male
Molecular Sequence Data
Onchocerca volvulus / drug effects*,  genetics
Onchocerciasis / drug therapy,  parasitology
Selection, Genetic*
Chemical
Reg. No./Substance:
0/ATP-Binding Cassette Transporters; 0/Antiparasitic Agents; 0/Helminth Proteins; 70288-86-7/Ivermectin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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