Genomics of anthelmintic resistance in Haemonchus contortus and evidences for DNA methylation

Abstract

The main losses in sheep production are caused by gastrointestinal nematodes, mainly Haemonchus contortus, and by anthelmintic resistance. Currently, monepantel is the only effective anthelmintic in several flocks. Resistance results from increased frequency of favorable genes to survival in population. Despite advancements of the candidate gene approaches to associate genetic polymorphisms to resistance, since it is a quantitative trait, it will only be well understood by genomic strategies. Furthermore, since epigenetics, such as DNA methylation, also contributes to the phenotypic variation, their importance to parasite physiology and to the development of resistance still needs to be better understood. So, in this project, monepantel resistance will be induced in H. contortus and selective sweeps will be detected by genomic sequencing of larvae pool (Pool-Seq), to identify genes under selection. In addition, the existence of DNA methylation will be in silico investigated. The goal of this study is to identify genomic molecular markers associated with resistance to monepantel, to contribute to the early diagnosis and monitoring of resistance and to maintain the effectiveness of monepantel in sheep flocks. Furthermore, the studies on metabolic pathways and epigenetic events involved in anthelmintic resistance will seek for alternative treatments and for new targets of drugs. (AU)