title: Combined analysis of DNA methylome and transcriptome reveal novel candidate genes with susceptibility to bovine Staphylococcus aureus subclinical mastitis.
abstract: Subclinical mastitis is a widely spread disease of lactating cows. Its major pathogen is Staphylococcus aureus (S. aureus). In this study, we performed genome-wide integrative analysis of DNA methylation and transcriptional expression to identify candidate genes and pathways relevant to bovine S. aureus subclinical mastitis. The genome-scale DNA methylation profiles of peripheral blood lymphocytes in cows with S. aureus subclinical mastitis (SA group) and healthy controls (CK) were generated by methylated DNA immunoprecipitation combined with microarrays. We identified 1078 differentially methylated genes in SA cows compared with the controls. By integrating DNA methylation and transcriptome data, 58 differentially methylated genes were shared with differently expressed genes, in which 20.7% distinctly hypermethylated genes showed down-regulated expression in SA versus CK, whereas 14.3% dramatically hypomethylated genes showed up-regulated expression. Integrated pathway analysis suggested that these genes were related to inflammation, ErbB signalling pathway and mismatch repair. Further functional analysis revealed that three genes, NRG1, MST1 and NAT9, were strongly correlated with the progression of S. aureus subclinical mastitis and could be used as powerful biomarkers for the improvement of bovine mastitis resistance. Our studies lay the groundwork for epigenetic modification and mechanistic studies on susceptibility of bovine mastitis.
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture &National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, 100193, Beijing, P.R. China.
authors.forename: Minyan
authors.initials: M
authors.lastname: Song
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture &National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, 100193, Beijing, P.R. China.|Department of Animal &Avian Sciences, University of Maryland, College Park, Maryland, 20742, USA.
authors.forename: Yanghua
authors.initials: Y
authors.lastname: He
authors.affiliation: Guangzhou Genedenovo Biotechnology Co., Ltd., Guangzhou, China.
authors.forename: Huangkai
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture &National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, 100193, Beijing, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Beijing Sanyuan Breeding Technology Co. Ltd., Capital Agribusiness Group, Beijing, China.
authors.forename: Xizhi
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture &National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, 100193, Beijing, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
mesh_terms: D000123:Acetyltransferases / Q000235:genetics; D000818:Animals; D015415:Biomarkers; D002417:Cattle / Q000235:genetics* / Q000382:microbiology; D002460:Cell Line; D019175:DNA Methylation; D005260:Female; D020022:Genetic Predisposition to Disease; D017228:Hepatocyte Growth Factor / Q000235:genetics; D047468:Immunoprecipitation; D007249:Inflammation; D007774:Lactation; D008414:Mastitis, Bovine / Q000235:genetics* / Q000382:microbiology; D008892:Milk; D020890:Neuregulin-1 / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D013203:Staphylococcal Infections / Q000235:genetics / Q000662:veterinary*; D013211:Staphylococcus aureus / Q000472:pathogenicity*
chemical_list: D000123:Acetyltransferases; D015415:Biomarkers; D017228:Hepatocyte Growth Factor; D020890:Neuregulin-1; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C082332:macrophage stimulating protein