Genome-wide association study to identify candidate genes and biological pathways related to milk yield and composition in sheep based on gene-set enrichment analysis
associated with milk related traits and somatic cell scores through genome-wide association study based on gene-set enrichment analysis in Valle del Belice sheep breed. To this end, the genotypic information of 476 sheep of this breed along with phenotypic records related to production traits including milk yield and milk composition were evaluated using PLINK v. 1.9. After performing various quality control steps, finally 42285 SNP markers in 426 animals were used for follow-up analysis. The results of the genome wide association study (GWAS) showed that 1830, 1577, 2186, 793, 710 and 1063 SNP markers are associated with milk yield, amount and percentage of fat, amount and percentage of protein and somatic cell score in Valle del Belice sheep, respectively (P-value ≤ 0.05). The results of the analysis based on gene-set enrichment led to the identification of pathways (candidate genes) of lipid phosphorylation (including TTC7B candidate gene), lipoprotein transport (ZDHHC17 gene), regulation of calcium ion transport (ATP2B2 gene) and pathway of peptide hormone processing (PCSK6 gene) associated with milk yield; regulation of fatty acid metabolic process (IRS1 and SLC45A3 genes) related to milk fat; the signal transduction by protein phosphorylation (ERCC6 gene) and the pathway of sulfur amino acid metabolic process (NOX4 gene) in relationship with milk protein; and finally the pathways of positive regulation of response to biotic stimulus (PRKCA gene), response pathway to external stimuli (CACNA2D1 gene), regulation of response to stress (EGFR and HSP90B1 genes) and response to bacterium (candidate gene ANXA3) related to somatic cell score.
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