Gene co-expression networks from RNA sequencing of dairy cattle identifies genes and pathways affecting feed efficiency

Abstract Background Selection for feed efficiency is crucial for overall profitability and sustainability in dairy cattle production. Key regulator genes and genetic markers derived from co-expression networks underlying feed efficiency could be included in the genomic selection of the best cows. The present study identified co-expression networks associated with high and low feed efficiency and their regulator genes in Danish Holstein and Jersey cows. RNA-sequencing data from Holstein and Jersey cows with high and low residual feed intake (RFI) and treated with two diets (low and high concentrate) were used. Approximately 26 million and 25 million pair reads were mapped to bovine reference genome for Jersey and Holstein breed, respectively. Subsequently, the gene count expressions data were analysed using a Weighted Gene Co-expression Network Analysis (WGCNA) approach. Functional enrichment analysis from Ingenuity® Pathway Analysis (IPA®), ClueGO application and STRING of these modules was performed to identify relevant biological pathways and regulatory genes. Results WGCNA identified two groups of co-expressed genes (modules) significantly associated with RFI and one module significantly associated with diet. In Holstein cows, the salmon module with module trait relationship (MTR) = 0.7 and the top upstream regulators ATP7B were involved in cholesterol biosynthesis, steroid biosynthesis, lipid biosynthesis and fatty acid metabolism. The magenta module has been significantly associated (MTR = 0.51) with the treatment diet involved in the triglyceride homeostasis. In Jersey cows, the lightsteelblue1 (MTR = − 0.57) module controlled by IFNG and IL10RA was involved in the positive regulation of interferon-gamma production, lymphocyte differentiation, natural killer cell-mediated cytotoxicity and primary immunodeficiency. Conclusion The present study provides new information on the biological functions in liver that are potentially involved in controlling feed efficiency. The hub genes and upstream regulators (ATP7b, IFNG and IL10RA) involved in these functions are potential candidate genes for the development of new biomarkers. However, the hub genes, upstream regulators and pathways involved in the co-expressed networks were different in both breeds. Hence, additional studies are required to investigate and confirm these findings prior to their use as candidate genes

RNA-Seq transcriptomics and pathway analyses reveal potential regulatory genes and molecular mechanisms in high- and low-residual feed intake in Nordic dairy cattle

BACKGROUND: The selective breeding of cattle with high-feed efficiencies (FE) is an important goal of beef and dairy cattle producers. Global gene expression patterns in relevant tissues can be used to study the functions of genes that are potentially involved in regulating FE. In the present study, high-throughput RNA sequencing data of liver biopsies from 19 dairy cows were used to identify differentially expressed genes (DEGs) between high- and low-FE groups of cows (based on Residual Feed Intake or RFI). Subsequently, a profile of the pathways connecting the DEGs to FE was generated, and a list of candidate genes and biomarkers was derived for their potential inclusion in breeding programmes to improve FE. RESULTS: The bovine RNA-Seq gene expression data from the liver was analysed to identify DEGs and, subsequently, identify the molecular mechanisms, pathways and possible candidate biomarkers of feed efficiency. On average, 57 million reads (short reads or short mRNA sequences < ~200 bases) were sequenced, 52 million reads were mapped, and 24,616 known transcripts were quantified according to the bovine reference genome. A comparison of the high- and low-RFI groups revealed 70 and 19 significantly DEGs in Holstein and Jersey cows, respectively. The interaction analysis (high vs. low RFI x control vs. high concentrate diet) showed no interaction effects in the Holstein cows, while two genes showed interaction effects in the Jersey cows. The analyses showed that DEGs act through certain pathways to affect or regulate FE, including steroid hormone biosynthesis, retinol metabolism, starch and sucrose metabolism, ether lipid metabolism, arachidonic acid metabolism and drug metabolism cytochrome P450. CONCLUSION: We used RNA-Seq-based liver transcriptomic profiling of high- and low-RFI dairy cows in two breeds and identified significantly DEGs, their molecular mechanisms, their interactions with other genes and functional enrichments of different molecular pathways. The DEGs that were identified were the CYP’s and GIMAP genes for the Holstein and Jersey cows, respectively, which are related to the primary immunodeficiency pathway and play a major role in feed utilization and the metabolism of lipids, sugars and proteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-3622-9) contains supplementary material, which is available to authorized users

Association of respiratory symptoms and lung function with occupation in the multinational Burden of Obstructive Lung Disease (BOLD) study

Background Chronic obstructive pulmonary disease has been associated with exposures in the workplace. We aimed to assess the association of respiratory symptoms and lung function with occupation in the Burden of Obstructive Lung Disease study. Methods We analysed cross-sectional data from 28 823 adults (≥40 years) in 34 countries. We considered 11 occupations and grouped them by likelihood of exposure to organic dusts, inorganic dusts and fumes. The association of chronic cough, chronic phlegm, wheeze, dyspnoea, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)/FVC with occupation was assessed, per study site, using multivariable regression. These estimates were then meta-analysed. Sensitivity analyses explored differences between sexes and gross national income. Results Overall, working in settings with potentially high exposure to dusts or fumes was associated with respiratory symptoms but not lung function differences. The most common occupation was farming. Compared to people not working in any of the 11 considered occupations, those who were farmers for ≥20 years were more likely to have chronic cough (OR 1.52, 95% CI 1.19–1.94), wheeze (OR 1.37, 95% CI 1.16–1.63) and dyspnoea (OR 1.83, 95% CI 1.53–2.20), but not lower FVC (β=0.02 L, 95% CI −0.02–0.06 L) or lower FEV1/FVC (β=0.04%, 95% CI −0.49–0.58%). Some findings differed by sex and gross national income. Conclusion At a population level, the occupational exposures considered in this study do not appear to be major determinants of differences in lung function, although they are associated with more respiratory symptoms. Because not all work settings were included in this study, respiratory surveillance should still be encouraged among high-risk dusty and fume job workers, especially in low- and middle-income countries.publishedVersio

Interchangeability between methane measurements in dairy cows assessed by comparing precision and agreement of two non-invasive infrared methods

In this study we assess the interchangeability and statistical agreement of two prevalent instruments from the non-invasive "sniffer" method and compare their precision. Furthermore, we develop and validate an effective algorithm for aligning time series data from multiple instruments to remove the effects of variable and fixed time shifts from the instrument comparison. The CH4 and CO2 gas concentrations for both instruments were found to differ for population means (P < 0.05) and intra-cow variation (precision) (P < 0.05) and for inter-cow variation (P < 0.05). The CH4 and CO2 gas concentrations from both instruments can be used interchangeably to increase statistical power for example, in genetic evaluations, provided sources of disagreement are corrected through calibration and standardisation. Additionally, averaging readings of cows over a longer period of time (one week) is an effective noise reduction technique which provides phenotypes with considerable inter-cow variation