Sheep chromosome 3 (Oar3) has the largest number of QTLs reported to be significantly associated with resistance to gastro-intestinal nematodes. This study aimed to identify single nucleotide polymorphisms (SNPs) within candidate genes located in sheep chromosome 3 as well as genes involved in major immune pathways. A total of 41 SNPs were identified across 38 candidate genes in a panel of unrelated sheep and genotyped in 713 animals belonging to 22 breeds across Asia, Europe and South America. The variations and evolution of immune pathway genes were assessed in sheep populations across these macro-environmental regions that significantly differ in the diversity and load of pathogens. The mean minor allele frequency (MAF) did not vary between Asian and European sheep reflecting the absence of ascertainment bias. Phylogenetic analysis revealed two major clusters with most of South Asian, South East Asian and South West Asian breeds clustering together while European and South American sheep breeds clustered together distinctly. Analysis of molecular variance revealed strong phylogeographic structure at loci located in immune pathway genes, unlike microsatellite and genome wide SNP markers. To understand the influence of natural selection processes, SNP loci located in chromosome 3 were utilized to reconstruct haplotypes, the diversity of which showed significant deviations from selective neutrality. Reduced Median network of reconstructed haplotypes showed balancing selection in force at these loci. Preliminary association of SNP genotypes with phenotypes recorded 42 days post challenge revealed significant differences (P<0.05) in fecal egg count, body weight change and packed cell volume at two, four and six SNP loci respectively. In conclusion, the present study reports strong phylogeographic structure and balancing selection operating at SNP loci located within immune pathway genes. Further, SNP loci identified in the study were found to have potential for future large scale association studies in naturally exposed sheep populations.

ABSTRAKPemberian antihelminth setengah dosis merupakan metode sederhana untuk deteksi dini terjadinya resistensi parasit yang menginfeksi ruminansia kecil. Ketika kegagalan antihelminth secara tunggal pada domba asli dari Indonesia, kombinasi antihelminth dari kelas kimia dengan mekanisme yang berbeda sebagai salah satu strategi alternatif pengendalian parasit. Penelitian ini membandingkan efektivitas ivermectin (IVM) dan albendazole (ABZ) baik yang diberikan secara terpisah dengan pemberian satu dan setengah dosis maupun dikombinasikan pada domba secara yang alami terinfeksi Ostertagia. , and control groups. The treatment effectiveness was determined using the Faecal egg count reduction (FECR) on before and after 7, 14, 21, 28, 35, and 42 days of treatment. FECR of half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, and both combined ranged from 78100, 96100, -7189, -52164, and 54100, respectively. The results showed that full-dose IVM was the most effective to against Ostertagia until 42 days and followed the combined that effective until 28 days. Half-dose and full-dose ABZ weren't effective to against Ostertagia.

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