Genetic markers of anthelmintic resistance in gastrointestinal parasites of ruminants

QH426 Genetics;S Agriculture (General);SF600 Veterinary Medicine

McIntyre, Jennifer Ruth ; Agriculture and Horticulture Development Board (AGHODEVB) ; Devaney, E.

University:University of Glasgow

Department:Institute of Biodiversity Animal Health and Comparative Medicine

关键词: 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.;   

Others  :  http://theses.gla.ac.uk/79021/1/2020McIntyreJenPhD.pdf

来源: University of Glasgow

【 摘 要 】

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.