Candidate Gene Approach for Parasite Resistance in Sheep – Variation in Immune Pathway Genes and Association with Fecal Egg Count

Abstract

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.

Single-nucleotide polymorphism-based genetic diversity analysis of the Kilakarsal and Vembur sheep breeds

“…Similar result was reported with the global F IS of 0.018 in the sheep population including Madras Red, Mecheri, and Pattanam sheep of Tamil Nadu [11] and the estimated mean F IS values across 19 short tandem repeat loci were found to be positive in wild Punjab Urial sheep and domestic sheep from West Asia breeds except Krainer Steinschaf and Madras Red which had F IS values of −0.005 and −0.001, respectively [14]. The global F IS observed in the present study is much lower than the previous reports in European sheep (0.123) [15], Nigerian sheep (0.335) [16], and Bulgarian sheep (0.288) [17].…”

Growth hormone polymorphisms and growth traits in Chinese Tibetan sheep Ovis aries

“…These growth traits are affected by many factors, such as genotype, sex, age, breed, nutritional level, and other environmental factors (Gui et al, 2014). Accumulating evidence suggests that the candidate gene approach is one of many methods suitable for analysis of the association between gene polymorphism and phenotypes, which is a promising strategy for the genetic improvement of economically important quantitative traits (Edmunds et al, 2009;Periasamy et al, 2014). GH is a single-chain polypeptide hormone mainly secreted by somatotropes of the anterior pituitary gland and is an important regulator of somatic growth in almost all vertebrates Rak and Gregoraszczuk, 2008;Delgadin et al, 2015;Odle et al, 2015).…”

Immune and other factors modulating host resistance against gastrointestinal nematode parasites in sheep

“…Among sheep breeds a considerable variation on their ability to resist GIN has been demonstrated (Periasamy et al, 2014). Similarly, a genetic variation even within the animals of the same breed has been reported for sheep populations of Merino, Romney, Scottish Blackface and Feral Soay sheep (Periasamy et al, 2014). Host resistance is a heritable feature with wide variability among individuals.…”

“…The OAR-12 remains an interesting candidate, because of a 10-Mbp region affecting FEC both after the first and the second infection (Salle et al, 2012). Periasamy et al (2014) reported strong phylogeographic structure and balancing selection operating SNPs located within immune pathway genes. This study identified a total of 41 SNPs within 38 candidate genes, located in sheep chromosome 3, as well as in other genes involved in major immune pathways, in a panel of 713 unrelated sheep, belonging to 22 breeds across Asia, Europe and South America.…”

“…Several quantitative trait loci (QTLs) mapping studies on parasite resistance characteristics have been reported in sheep. The objective of QTL studies is to identify underlying causative molecular markers, such as single nucleotide polymorphisms (SNPs) which correlate with an observed trait (Periasamy et al, 2014). The QTL analysis is a powerful method to understand the genotype -phenotype relationship and has up to date identified a number of traits indicative of resistance (Silva et al, 2012;Marshall et al, 2012).…”