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RNA-Seq reveals 10 novel promising candidate genes affecting milk protein concentration in the Chinese Holstein population.

ABSTRACT: Paired-end RNA sequencing (RNA-Seq) was used to explore the bovine transcriptome from the mammary tissue of 12 Chinese Holstein cows with 6 extremely high and 6 low phenotypic values for milk protein percentage. We defined the differentially expressed transcripts between the two comparison groups, extremely high and low milk protein percentage during the peak lactation (HP vs LP) and during the non-lactating period (HD vs LD), respectively. Within the differentially expressed genes (DEGs), we detected 157 at peak lactation and 497 in the non-lactating period with a highly significant correlation with milk protein concentration. Integrated interpretation of differential gene expression indicated that SERPINA1, CLU, CNTFR, ERBB2, NEDD4L, ANG, GALE, HSPA8, LPAR6 and CD14 are the most promising candidate genes affecting milk protein concentration. Similarly, LTF, FCGR3A, MEGF10, RRM2 and UBE2C are the most promising candidates that in the non-lactating period could help the mammary tissue prevent issues with inflammation and udder disorders. Putative genes will be valuable resources for designing better breeding strategies to optimize the content of milk protein and also to provide new insights into regulation of lactogenesis.

SUBMITTER: Li C

PROVIDER: S-EPMC4890585 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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RNA-Seq reveals 10 novel promising candidate genes affecting milk protein concentration in the Chinese Holstein population.

Li Cong C Cai Wentao W Zhou Chenghao C Yin Hongwei H Zhang Ziqi Z Loor Juan J JJ Sun Dongxiao D Zhang Qin Q Liu Jianfeng J Zhang Shengli S

Scientific reports 20160602

Paired-end RNA sequencing (RNA-Seq) was used to explore the bovine transcriptome from the mammary tissue of 12 Chinese Holstein cows with 6 extremely high and 6 low phenotypic values for milk protein percentage. We defined the differentially expressed transcripts between the two comparison groups, extremely high and low milk protein percentage during the peak lactation (HP vs LP) and during the non-lactating period (HD vs LD), respectively. Within the differentially expressed genes (DEGs), we de ...[more]

PMID: 27254118

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Project description:Although the chemical, physical, and nutritional properties of bovine milk have been extensively studied, only a few studies have attempted to characterize milk-synthesizing genes using RNA-seq data. RNA-seq data was collected from 21 Holstein samples, along with group information about milk production ability; milk yield; and protein, fat, and solid contents. Meta-analysis was employed in order to generally characterize genes related to milk production. In addition, we attempted to investigate the relationship between milk related traits, parity, and lactation period. We observed that milk fat is highly correlated with lactation period; this result indicates that this effect should be considered in the model in order to accurately detect milk production related genes. By employing our developed model, 271 genes were significantly (false discovery rate [FDR] adjusted p-value<0.1) detected as milk production related differentially expressed genes. Of these genes, five (albumin, nitric oxide synthase 3, RNA-binding region (RNP1, RRM) containing 3, secreted and transmembrane 1, and serine palmitoyltransferase, small subunit B) were technically validated using quantitative real-time polymerase chain reaction (qRT-PCR) in order to check the accuracy of RNA-seq analysis. Finally, 83 gene ontology biological processes including several blood vessel and mammary gland development related terms, were significantly detected using DAVID gene-set enrichment analysis. From these results, we observed that detected milk production related genes are highly enriched in the circulation system process and mammary gland related biological functions. In addition, we observed that detected genes including caveolin 1, mammary serum amyloid A3.2, lingual antimicrobial peptide, cathelicidin 4 (CATHL4), cathelicidin 6 (CATHL6) have been reported in other species as milk production related gene. For this reason, we concluded that our detected 271 genes would be strong candidates for determining milk production.

Project description:BackgroundKetosis in dairy cattle has been shown to cause a high morbidity in the farm and substantial financial losses to dairy farmers. Ketosis symptoms, however, are difficult to identify, therefore, the amount of ketone bodies (mainly β-hydroxybutyric acid, BHB) is used as an indicator of subclinical ketosis in cows. It has also been shown that milk BHB concentrations have a strong correlation with ketosis in dairy cattle. Mid-infrared spectroscopy (MIR) has recently became a fast, cheap and high-throughput method for analyzing milk components. The aim of this study was to perform a genome-wide association study (GWAS) on the MIR-predicted milk BHB to identify genomic regions, genes and pathways potentially affecting subclinical ketosis in North American Holstein dairy cattle.ResultsSeveral significant regions were identified associated with MIR-predicted milk BHB concentrations (indicator of subclinical ketosis) in the first lactation (SCK1) and second and later lactations (SCK2) in Holstein dairy cows. The strongest association was located on BTA6 for SCK1 and BTA14 on SCK2. Several SNPs on BTA6 were identified in regions and variants reported previously to be associated with susceptibility to ketosis and clinical mastitis in Jersey and Holstein dairy cattle, respectively. One highly significant SNP on BTA14 was found within the DGAT1 gene with known functions on fat metabolism and inflammatory response in dairy cattle. A region on BTA6 and three SNPs on BTA20 were found to overlap between SCK1 and SCK2. However, a novel region on BTA20 (55-63 Mb) for SCK2 was also identified, which was not reported in previous association studies. Enrichment analysis of the list of candidate genes within the identified regions for MIR-predicted milk BHB concentrations yielded molecular functions and biological processes that may be involved in the inflammatory response and lipid metabolism in dairy cattle.ConclusionsThe results of this study confirmed several SNPs and genes identified in previous studies as associated with ketosis susceptibility and immune response, and also found a novel region that can be used for further analysis to identify causal variations and key regulatory genes that affect clinical/ subclinical ketosis.

Dataset Information

RNA-Seq reveals 10 novel promising candidate genes affecting milk protein concentration in the Chinese Holstein population.

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RNA-Seq reveals 10 novel promising candidate genes affecting milk protein concentration in the Chinese Holstein population.

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