Identification of candidate genes affecting chronic subclinical mastitis in Norwegian Red cattle: combining genome-wide association study, topologically associated domains and pathway enrichment analysis

Abstract

The aim of this study was to identify genes associated with chronic subclinical mastitis (SCM) in Norwegian Red (NR) cattle. Twelve SCM traits defined based on fixed threshold for test-day somatic cell count (SCC) were, together with lactation-average somatic cell score (LSCS) used for association and pathway enrichment analyses. A GWAS was performed on 3795 genotyped NR bulls with 777K SNP data and phenotypic information from 7 300 847 test-day SCC observations from 3 543 764 cows. At 5% chromosome-wide significance level 36 unique SNP were detected to be associated with one or more of the traits. These SNPs were analysed for linked genes using genomic positions of topologically associated domains (TAD). For the SCM traits with SCC >50 000 and >100 000 cells/ml on two test-days in a row and LSCS, the same top significant genes were identified – checkpoint clamp loader component (RAD17) and cyclin B1 (CCNB1). The SCM traits with SCC >250 000, 300 000, 350 000 or 400 000 cells/ml on two test-days in a row and D400 (number of days before the first case with SCC >400 000 cells/ml) displayed similar top significant genes: acyl-CoA thioesterase 2 and 4 (ACOT2; ACOT4). For the traits SCM200_3 (SCC >200 000 cells/ml on three test-days in a row) and SCM150, SCM200 (SCC >150 000; 200 000 cells/ml on two test-days in a row) a group of chemokine (C–X–C motif) ligand genes and the Fos proto-oncogene, AP-1 transcription factor subunit (FOS) gene, were identified. Further functional studies of these identified candidate genes are necessary to clarify their actual role in development of chronic SCM in NR cattle.