Association analysis of immune response loci related to Haemonchus contortus exposure in sheep and goats using a targeted approach

Abstract

Haemonchus contortus infections are an important source of animal production loss to livestock industry. Genetics of helminth resistance involves a complex set of factors related to the host immune response. The increasing use of genetic markers such as single nucleotide polymorphisms (SNPs) in genome wide association studies (GWAS) offers the potential to identify loci or regions associated with nematode resistance in small ruminants. The aims of this study were: (1) to use a targeted sequencing approach to identify SNPs in 100 genes related to immune response during Haemonchus contortus exposure in growing males of St. Croix, Katahdin and Dorper sheep, and in Kiko, Boer and Spanish goats, and (2) to perform an association analysis for fecal egg count (FEC), packed cell volume (PCV), immunoglobulin levels (IgA, IgG and IgM) and average daily gain (ADG) in the populations under study. After quality control (call rate < 95%, MAF < 0.05), 1356 SNPs (sheep) and 1,029 SNPs (goats) were used for the association analysis. A mixed model was used to analyze the phenotypic information. To control for population structure, the genomic relationship matrix (G) calculated from marker information was included in the model. Fixed effects included year and breed. Bonferroni correction was used to control for multiple testing. For sheep, SNPs located on OAR1 (42487870, 42489606) and OAR2 (192231080, 26321541) were significantly associated with IgM, ADG, and FEC. For goats, SNPs on CHR3 (42898132) and CHR22 (23066762) were associated with ADG and IgM. In both species, no significant associations were found for IgA, IgG and PCV. The results from this study revealed genes involved in the immune response to H. contortus exposure and provide additional SNP marker information that has potential to aid selection of resistance to gastrointestinal parasites in sheep and goats from different breeds. Significant SNPs within IL12RB2, NFIL3 and STAT4 genes could be potential markers for IgM, FEC and ADG in sheep populations. For goats, potential markers for IgM and ADG were identified within IL5RA and IL12RB2 genes. These results could be directly implemented in the populations used in this study, however, they should be validated before using these markers in other sheep and goat populations.