Genomic variation and molecular mechanisms of the host response to gastrointestinal nematodes in small ruminants
Abstract: Gastrointestinal nematode (GIN) infections are one of the major constrains for sheep and goat production worldwide. One of the promising control strategies is the genetic selection for resistant animals as there are no issues due to anthelmintic resistance and it aligns to demands for chemical-free food. Exploring possible phenotypic and genomic markers that could be used in breeding scheme besides understanding the mechanisms responsible for resistance were the main goals of this thesis. Thesis consists of General introduction, a brief description of GIN biology and methods to control GIN with focus on phenotypic and genomic markers, four papers and General discussion. In paper Ⅰ, a systematic review and meta-analysis were conducted to re-analyse and summarize the findings on immunoglobulins response to GIN in the literature and discuss the potential to use immunoglobulins as biomarkers of the host resistance. A conceptual model summarizing the role of immunoglobulins in resistance to GIN is proposed. In paper Ⅱ, transcriptome profiling of the abomasal mucosa and lymph node tissues were compared between non-infected, resistant and susceptible Creole goats experimentally infected with Haemonchus contortus. Results indicated that the maintenance of the integrity of the mucosa has probably the priority for the host at late infection stage. In paper Ⅲ, the dynamics of the response of the abomasal mucosa of resistant and susceptible Creole goats experimentally infected with H. contortus were compared. The immune response was activated through many relevant pathways including the Th1 immune response at different time post-infection. Interestingly, the results showed a simultaneous time series activation of Th2 related genes in resistant compared to susceptible kids. In paper Ⅳ, the genomic variants of Creole goats resistant and susceptible to H. contortus were discovered from RNAsequencing data at four different times post-infection. Single nucleotide polymorphisms, insertions and deletions that distinguish the resistant and the susceptible groups were identified and characterized through functional analysis. The T cell receptor signalling pathway was one of the top significant pathways that distinguish the resistant from the susceptible group with genomic variants in 78% of genes in this pathway.
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