Genetic and molecular basis of triclabendazole resistance in Fasciola hepatica

Tue10  Apr04:15pm(30 mins)
Where:
Stream 3 - Physics 0.15 Main
Keynote Speaker:
Prof Jane Hodgkinson

Authors

J Hodgkinson1
1 University of Liverpool, UK

Discussion

The liver fluke, Fasciola hepatica, has a substantial impact on the health and welfare of livestock, particularly cattle and sheep and is recognised by WHO as an important zoonosis. With predictions for further increases in prevalence due to a changing climate, increased animal movement and changes in land management F. hepatica infection is set to have a greater impact on livestock productivity and human health in future. This is compounded by the problem of triclabendazole (TCBZ) resistance, the only drug to target the highly pathogenic juvenile fluke migrating through the liver. This paper will report a series of studies we have taken to better understand the genetic basis of TCBZ resistance in F. hepatica. We have used single miracidial:snail infections of F. hepatica to generate and characterise clonal parental lines of TCBZ-resistant (TCBZ-R) and TCBZ-susceptible (TCBZ-S) liver fluke. These parental clones have been used to generate a cross between TCBZ-R and –S parasites and, given that F. hepatica is hermaphrodite, a panel of neutral microsatellite markers was used to track those F1 parasites that undergone cross fertilization. By comparing the frequency of SNP alleles derived from the resistant parental clone and linked to the TCBZ resistance loci in pooled, phenotyped F2 recombinants we have localised six regions of the genome under selection. Using a sequence capture approach we have identified SNP markers in loci under selection and we are currently genotyping ~750 F2 liver fluke to establish if TCBZ resistance is a dominant or recessive trait. In addition this work will highlight our enhanced F. hepatica genome draft, our work to generate a genetic linkage map and our plans to finer-scale map resistance loci using field isolates.
Schedule

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