Lactation Associated Genes Revealed in Holstein Dairy Cows by Weighted Gene Co-Expression Network Analysis (WGCNA)

SIMPLE SUMMARY: Weighted gene coexpression network analysis (WGCNA) is a novel approach that can quickly analyze the relationships between genes and traits. In the past few years, studies on the gene expression changes of dairy cow mammary glands were only based on transcriptome comparisons between two lactation stages. Few studies focused on the relationships between gene expression of the dairy mammary gland and lactation stage or milk composition in a lactation cycle. In this study, we detected milk yield and composition in a lactation cycle. For the first time, we constructed a gene coexpression network using WGCNA on the basis of 18 gene expression profiles during six stages of a lactation cycle by transcriptome sequencing, generating 10 specific modules. Genes in each module were performed with gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Module–trait relationship analysis showed a series of potential candidates related to milk yield and composition. The current study provides an important theoretical basis for the further molecular breeding of dairy cows. ABSTRACT: Weighted gene coexpression network analysis (WGCNA) is a novel approach that can quickly analyze the relationships between genes and traits. In this study, the milk yield, lactose, fat, and protein of Holstein dairy cows were detected in a lactation cycle. Meanwhile, a total of 18 gene expression profiles were detected using mammary glands from six lactation stages (day 7 to calving, −7 d; day 30 post-calving, 30 d; day 90 post-calving, 90 d; day 180 post-calving, 180 d; day 270 post-calving, 270 d; day 315 post-calving, 315 d). On the basis of the 18 profiles, WGCNA identified for the first time 10 significant modules that may be related to lactation stage, milk yield, and the main milk composition content. Genes in the 10 significant modules were examined with gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The results revealed that the galactose metabolism pathway was a potential candidate for milk yield and milk lactose synthesis. In −7 d, ion transportation was more frequent and cell proliferation related terms became active. In late lactation, the suppressor of cytokine signaling 3 (SOCS3) might play a role in apoptosis. The sphingolipid signaling pathway was a potential candidate for milk fat synthesis. Dairy cows at 315 d were in a period of cell proliferation. Another notable phenomenon was that nonlactating dairy cows had a more regular circadian rhythm after a cycle of lactation. The results provide an important theoretical basis for the further molecular breeding of dairy cows.