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Stellenbosch University (2017)

A genome-wide association study on mechanisms underlying genetic resistance to gastrointestinal parasites in goats, Zimbabwe

Zvinorova, Plaxedis I.

Titre : A genome-wide association study on mechanisms underlying genetic resistance to gastrointestinal parasites in goats, Zimbabwe

Auteur : Zvinorova, Plaxedis I.

Université de soutenance : Stellenbosch University

Grade : Doctor of Philosophy in Animal Sciences 2017

Genome wide association studies (GWAS) have evolved into powerful tools for investigating the genetic association of complex traits, such as gastrointestinal parasite (GIN) resistance. Knowledge on genes associated with GIN resistance can provide information for use in breeding programs. The objective of the study was to identify markers associated with resistance in goats, through the following specific objectives : i) assessing the level of knowledge on GIN, management and control of GIN, ii) determining the prevalence and risk factors of GIN, iii) determining genetic diversity and population structure of goats in Zimbabwe and iv) investigating genomic loci associated with GIN resistance traits using a genome-wide association analyses (GWAS). Surveys were conducted in 135 households, using a pre-tested questionnaires in Chipinge (natural region (NR) I and II), Shurugwi (NR III), Binga and Tsholotsho (NR IV) and Matobo (NR V). GIN were ranked highest as the most common disease, with 57% of farmers not controlling or treating animals and 63% of farmers not having knowledge on the spread of GIN. A total of 580 blood and faecal samples were collected from goats from the same households, with additional sampling being conducted in the Research station flock. Highest prevalence was determined for Eimeria oocysts (43%) and Strongyles (31%). Area, season, sex and age significantly influenced patterns of GIN infections (P < 0.05). Prevalence was highest in goats from Chipinge and Binga, greater in wet than dry season and in males than females. High prevalences were observed for goats aged 1 and 6 years and the least for goats aged 3. Associated risk factors were also evaluated per area. A subset of the sampled animals (253) was genotyped using the Illumina Goat 50 K SNP beadchip. Population structure analyses were performed using ADMITXURE and PLINK. Five clusters were identified, with distinct populations of Binga and high levels of shared ancestry in goats from Tsholotsho and Matobo districts. Genetic parameters indicated high levels of genetic diversity based on observed (HE) and expected (HO), low linkage disequilibrium (r 2 = 0.03 - 0.18) and low FST (0.01 – 0.04). For genome-wide analyses, two approaches were used : i) single-SNP association using logarithm transformed faecal egg counts, ii) within-population association using case/control data. After quality control, 49 984 SNPs and 44 918 SNPs were available for genome-wide association analyses in GenAbel and PLINK respectively. The study confirmed that GIN resistance traits were heritable (0.27 - 0.56 i.e low - moderate). The analyses revealed significant multiple SNPs that were associated with Eimeria and Strongyles at the genome-wide level. Regions on chromosomes (chr) 4 (P = 2.66 x10-6 and P = 1.45 x10-5) for Eimeira and chr 29 (P = 9.93 x10-6) were found to be associated with GIN resistance, for the Eimeria and Strongyles traits. Genes annotated to the SNP positions were ORC5, DGKB and HRASLS5, respectively. The role of the genes have not been reported in previous studies or implicated in the involvement of biological pathways that have roles in eliciting responses towards GIN infections. Overally, the study demonstrates the utility of the Illumina Goat 50 K SNP, despite that the animals used in the study were not represented in the SNP discovery breeds. Knowledge of these genes and understanding the underlying mechanisms to GIN resistance can be used in the development of breeding programs and hence improve productivity.


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