Genetic markers of anthelmintic resistance in gastrointestinal parasites of ruminants

McIntyre, Jennifer Ruth (2020) Genetic markers of anthelmintic resistance in gastrointestinal parasites of ruminants. PhD thesis, University of Glasgow.

Abstract

Parasitic gastroenteritis is the primary production limiting disease of sheep in the UK and is a considerable welfare concern. A global problem, it is caused by nematode parasites and mixed species infections can be common. In the UK, the primary pathogen in growing lambs is Teladorsagia circumcincta, an abomasal parasite of small ruminants, causing severe pathology and reduced weight gain. T. circumcincta is expertly adapted to both the host and the farming year and control is extremely difficult. The majority of UK farmers will use anthelmintics to manage parasitic gastroenteritis. Nevertheless, anthelmintic resistance is increasing, reducing control options. Many farmers will now dose sheep with a macrocyclic lactone (e.g. ivermectin) to treat T. circumcincta as this species has developed resistance to multiple anthelmintic classes. Unfortunately, over fifty percent of farms in recent UK studies had detectable ivermectin resistance.

There is a pressing need to conserve anthelmintics for future use. However, the mechanism of ivermectin resistance is unknown, and the lack of a sensitive test for ivermectin resistance limits research into resistance spread and development. Many excellent studies have investigated ivermectin resistance in nematode parasites, however mutations responsible for ivermectin resistance remain elusive. The purpose of this PhD was to perform a genome wide association study to identify genomic regions under ivermectin selection within UK T. circumcincta field populations. L3 progeny were sequenced pre- and post-ivermectin treatment using next generation sequencing techniques (ddRAD-Seq and Pool-Seq) and population genetics analyses were performed.

Multiple loci were genetically differentiated between pre- and post-ivermectin populations. However, the reference genomes used were highly fragmented and the number of loci under selection cannot be concluded. Genes identified included those with neuronal functions, metabolic and regulatory genes. Many genes had associations with pharyngeal structures and chemosensory behaviour. Nevertheless, multiple copies of genes expected to be single copy were detected in both reference genomes and these may have affected read alignment and results. The work performed here provides an important basis for future studies, and has generated high quality next generation sequenced resources from two UK field populations of T. circumcincta.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Results in Chapter 3 have been published in two papers: McIntyre, J. et al., 2018 https://doi.org/10.1016/j.vetpar.2018.06.012 and Hamer, K. et al., 2019 https://doi.org/10.1016/j.prevetmed.2019.104752
• Keywords: Teladorsagia circumcincta, anthelmintic resistance, ivermectin, benzimidazoles, parasite genomics, parasitic gastroenteritis, bioinformatics, molecular biology, veterinary parasitology, sheep, ruminants, next generation sequencing, pool-Seq, ddRAD-Seq, genetic markers.
• Subjects: Q Science > QH Natural history > QH426 Genetics; S Agriculture > S Agriculture (General); S Agriculture > SF Animal culture > SF600 Veterinary Medicine
• Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
• Funder's Name: Agriculture and Horticulture Development Board (AGHODEVB), Biotechnology and Biological Sciences Research Council (BBSRC), Biotechnology and Biological Sciences Research Council (BBSRC)
• Supervisor's Name: Devaney, Professor E. and Laing, Dr. R.
• Date of Award: 2020
• Depositing User: Miss Jennifer McIntyre
• Unique ID: glathesis:2020-79021
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 11 Mar 2020 15:56
• Last Modified: 27 Apr 2022 08:50
• Thesis DOI: 10.5525/gla.thesis.79021
• URI: https://theses.gla.ac.uk/id/eprint/79021

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