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Contribution of the mutation rs8193069 in TLR4 to mastitis resistance and performance in Holstein cows in southern China.

ABSTRACT: Bovine mastitis has become increasingly important issues for farmers and consumers, leading to large economic losses in the dairy industry worldwide. Because treatment of mastitis is difficult and costly, improved mastitis resistance through selective breeding would be advantageous. The toll-like receptor 4 (TLR4) is an important player in recognising pathogens and activating immune responses. However, its roles in mastitis occurrence and the underlying molecular mechanisms are unclear. In this study, a single nucleotide polymorphism, rs8193069 (T → C) in TLR4 gene was detected in a Holstein cow resource population in southern China. Association analysis with 5-year production traits, haematology, and biochemistry parameters revealed that individuals with genotype CC had significantly lower somatic cell counts (SCC), lower fat percentage, but higher 305-day milk (p < 0.05) and total milk yield (p < 0.01). Both genotypes CC and CT had lower lymphocyte counts (#LYMPH) (p < 0.01) and basophil counts (#BASO) (p < 0.05) than TT. Genotype CC had a less level of triglyceride (p < 0.01) and creatine kinase (p < 0.05) than CT. Further analysis based on the production data revealed significant positive correlations between SCC and #LYMPH. Analysis of TLR4 protein structure and properties suggested that the missense mutation on the 674th amino acid from Thr to Ile reduced the flexibility and hydrophilicity of TIR domain, implying a weakened binding ability of TLR4 to its adaptors. In conclusion, allele C of rs8193069 was the major allele in Holstein cows that indicated a greater genetic potential to mastitis resistance and milk yields, probably via the LPS-TLR4 inflammatory signalling. This study offers a marker to improve mastitis resistance in the dairy cow population in southern China.

SUBMITTER: Chen H

PROVIDER: S-EPMC8788991 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMastitis is a very common disease in the dairy industry that producers encounter daily. Transcriptomics, using RNA-Sequencing (RNA - Seq) technology, can be used to study the functional aspect of mastitis resistance to identify animals that have a better immune response to mastitis. When the cow has mastitis, not only genes but also specific mRNA isoforms generated via alternative splicing (AS) could be differentially expressed (DE), leading to the phenotypic variation observed. Therefore, the objective of this study was to use large gap read mapping to identify mRNA isoforms DE between healthy and mastitic milk somatic cell samples (N = 12). These mRNA isoforms were then categorized based on being 1) annotated mRNA isoforms for gene name and length, 2) annotated mRNA isoforms with different transcript length and 3) novel mRNA isoforms of non - annotated genes.ResultsAnalysis identified 333 DE transcripts (with at least 2 mRNA isoforms annotated, with at least one being DE) between healthy and mastitic samples corresponding to 303 unique genes. Of these 333 DE transcripts between healthy and mastitic samples, 68 mRNA isoforms are annotated in the bovine genome reference (ARS.UCD.1.2), 249 mRNA isoforms had novel transcript lengths of known genes and 16 were novel transcript lengths of non - annotated genes in the bovine genome reference (ARS.UCD.1.2). Functional analysis including gene ontology, gene network and metabolic pathway analysis was performed on the list of 288 annotated and unique DE mRNA isoforms. In total, 67 significant metabolic pathways were identified including positive regulation of cytokine secretion and immune response. Additionally, numerous DE novel mRNA isoforms showed potential involvement with the immune system or mastitis. Lastly, QTL annotation analysis was performed on coding regions of the DE mRNA isoforms, identifying overlapping QTLs associated with clinical mastitis and somatic cell score.ConclusionThis study identified novel mRNA isoforms generated via AS that could lead to differences in the immune response of Holstein dairy cows and be potentially implemented in future breeding programs.

Project description:Staphylococcus aureus intramammary infection is one of the most common causes of chronic mastitis in dairy cows, whose development may be associated with epigenetic changes in the expression of important host defense genes. This study aimed to construct a genome-wide DNA methylation profile of the mammary gland of Chinese Holstein cows (n = 3) following experimentally induced S. aureus mastitis, and to explore the potential gene regulatory mechanisms affected by DNA methylation during S. aureus mastitis. DNA was extracted from S. aureus-positive (n = 3) and S. aureus-negative (n = 3) mammary gland quarters and subjected to methylation-dependent restriction-site associated DNA sequencing (Methyl-RAD Seq). Results showed that CmCGG/CmCWGG DNA methylation sites were unevenly distributed and concentrated on chromosomes 5, 11, and 19, and within intergenic regions and intron regions of genes. Compared with healthy control quarters, 9,181 significantly differentially methylated (DM) CmCGG sites and 1,790 DM CmCWGG sites were found in the S. aureus-positive quarters (P < 0.05, |log2FC| > 1). Furthermore, 363 CmCGG differently methylated genes (DMGs) and 301 CmCWGG DMGs (adjusted P < 0.05, |log2FC| > 1) were identified. Gene ontology and KEGG enrichment analysis indicated that CmCGG DMGs are involved in immune response pathways, while the CmCWGG DMGs were mainly enriched in gene ontology terms related to metabolism. The mRNAs of 526 differentially methylated CmCGG genes and 124 differentially methylated CmCWGG genes were also significantly differentially expressed (RNA-Seq data) in the same samples, herein denoted differentially methylated and expressed genes (DMEGs) (P < 0.05). Functional enrichment analysis of DMEGs revealed roles related to biological processes, especially the regulation of immune response to diseases. CmCGG DMEGs like IL6R, TNF, BTK, IL1R2, and TNFSF8 enriched in several immune-related GO terms and pathways indicated their important roles in host immune response and their potential as candidate genes for S. aureus mastitis. These results suggest potential regulatory roles for DNA methylation in bovine mammary gland processes during S. aureus mastitis and serves as a reference for future epigenetic regulation and mechanistic studies.

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Contribution of the mutation rs8193069 in TLR4 to mastitis resistance and performance in Holstein cows in southern China.

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