Screening Key Genes for Somatic Cell Count Trait in Dairy Cow Based on Genome-Wide Association Study and Metabolomics Analysis

Luo Zhongze; Zhang Ningyue; Li Ruirui; Ma Yun; Li Xinhai

doi:10.14083/j.issn.1001-4942.2025.03.021

Abstract：Somatic cell count trait is one of the important economical traits in dairy cow production and breeding.Screening important functional genes related to this trait and mining key molecular markers are of great significance to genetic improvement of the somatic cell count trait in dairy cow.In this study,the impor-tant genes and key metabolites affecting somatic cell count trait were screened by genome-wide association study(GWAS)combined with metabolomics analysis.Firstly,2 709 Holstein cows were genotyped using Illu-mina Bovine 50K SNP microarrays,and GWAS was performed using the genomic estimated breeding value(GEBV)for somatic cell count trait in dairy cow,and then six candidate genes including NPFFR2,ZNF831,SLC4A4,SLMO2,SKAP1 and CBX1 were screened out.KEGG pathway analysis revealed that the candidate genes were mainly enriched in the biological processes such as neuroactive ligand-receptor interactions,pan-creatic secretion,bile secretion,proximal tubule bicarbonate regeneration and Rap1 signaling pathway.Sec-ondly,the cows with extreme phenotype of high somatic cell count(Hscc)or low somatic cell count(Lscc)were selected for plasma metabolomics analysis based on liquid chromatography tandem mass spectrometry(LC-MS/MS),and 71 plasma significantly differential metabolites were screened out.Compared to the Hscc group,57 differentially expressed metabolites such as cortisol,aldosterone and cinnamic acid ethyl ester were up-regulated in the Lscc group,while 14 differentially expressed metabolites such as taurodeoxycholic acid and phasic acid were down-regulated.KEGG enrichment analysis revealed that the significantly differential metabo-lites were mainly enriched in the pathways of aldosterone-regulated sodium reabsorption,bile secretion,glyox-ylate and dicarboxylate metabolisms,and ketone body synthesis and degradation.The joint analysis of GW AS and metabolomics indicated that bile secretion was an important pathway in the regulation of somatic cell count trait,and the SLC4A4 gene affecting bile secretion process and bile secretion metabolite cortisol was the key gene and metabolite affecting the somatic cell count trait in dairy cows.The results of this study might provide important candidate genes and molecular markers for the genetic improvement of the somatic cell count trait in dairy cow.