Genome-wide association analysis identify candidate genes for feed efficiency and growth traits in Wenchang chickens.

BACKGROUND: Wenchang chickens are one of the most popular local chicken breeds in the Chinese chicken industry. However, the low feed efficiency is the main shortcoming of this breed. Therefore, there is a need to find a more precise breeding method to improve the feed efficiency of Wenchang chickens. In this study, we explored important candidate genes and variants for feed efficiency and growth traits through genome-wide association study (GWAS) analysis. RESULTS: Estimates of genomic heritability for growth and feed efficiency traits, including residual feed intake (RFI) of 0.05, average daily food intake (ADFI) of 0.21, average daily weight gain (ADG) of 0.24, body weight (BW) at 87, 95, 104, 113 days of age (BW87, BW95, BW104 and BW113) ranged from 0.30 to 0.44. Important candidate genes related to feed efficiency and growth traits were identified, such as PLCE1, LAP3, MED28, QDPR, LDB2 and SEL1L3 genes. CONCLUSION: The results identified important candidate genes for feed efficiency and growth traits in Wenchang chickens and provide a theoretical basis for the development of new molecular breeding technology.

Endoscopic application of magnetic compression anastomosis: a review.

Magnetic compression anastomosis (MCA) is a new method that provides sutureless passage construction for tubular organs. Due to the high recurrence rate of conventional endoscopic treatment and the high morbidity and mortality of surgical procedures, the MCA technique shows promise. The aim of this review is to comprehensively examine the literature related to the use of MCA in different gastrointestinal diseases over the past few years, categorizing them according to the anastomotic site and describing in detail the various methods of magnet delivery and the clinical outcomes of MCA. MCA is an innovative technique, and its use represents an advancement in the field of minimally invasive interventions. Comparison studies have shown that the anastomosis formed by MCA is comparable to or better than surgical sutures in terms of general appearance and histology. Although most of the current research has involved animal studies or studies with small populations, the safety and feasibility of MCA have been preliminarily demonstrated. Large prospective studies involving populations are still needed to guarantee the security of MCA. For technologies that have been initially used in clinical settings, effective measures should also be implemented to identify, even prevent, complications. Furthermore, specific commercial magnets must be created and optimized in this emerging area.

Understanding metabolic alterations after SARS-CoV-2 infection: insights from the patients' oral microenvironmental metabolites.

BACKGROUND: Coronavirus disease 2019 is a type of acute infectious pneumonia and frequently confused with influenza since the initial symptoms. When the virus colonized the patient's mouth, it will cause changes of the oral microenvironment. However, few studies on the alterations of metabolism of the oral microenvironment affected by SARS-CoV-2 infection have been reported. In this study, we explored metabolic alterations of oral microenvironment after SARS-CoV-2 infection. METHODS: Untargeted metabolomics (UPLC-MS) was used to investigate the metabolic changes between oral secretion samples of 25 COVID-19 and 30 control participants. To obtain the specific metabolic changes of COVID-19, we selected 25 influenza patients to exclude the metabolic changes caused by the stress response of the immune system to the virus. Multivariate analysis (PCA and PLS-DA plots) and univariate analysis (students' t-test) were used to compare the differences between COVID-19 patients and the controls. Online hiplot tool was used to perform heatmap analysis. Metabolic pathway analysis was conducted by using the MetaboAnalyst 5.0 web application. RESULTS: PLS-DA plots showed significant separation of COVID-19 patients and the controls. A total of 45 differential metabolites between COVID-19 and control group were identified. Among them, 35 metabolites were defined as SARS-CoV-2 specific differential metabolites. Especially, the levels of cis-5,8,11,14,17-eicosapentaenoic acid and hexanoic acid changed dramatically based on the FC values. Pathway enrichment found the most significant pathways were tyrosine-related metabolism. Further, we found 10 differential metabolites caused by the virus indicating the body's metabolism changes after viral stimulation. Moreover, adenine and adenosine were defined as influenza virus-specific differential metabolites. CONCLUSIONS: This study revealed that 35 metabolites and tyrosine-related metabolism pathways were significantly changed after SARS-CoV-2 infection. The metabolic alterations of oral microenvironment in COVID-19 provided new insights into its molecular mechanisms for research and prognostic treatment.

Identification of potential matrix metalloproteinase-2 inhibitors from natural products through advanced machine learning-based cheminformatics approaches.

Matrix metalloproteinase-2 (MMP-2) is capable of degrading Collage TypeIV in the vascular basement membrane and extracellular matrix. Studies have shown that MMP-2 is tightly associated with the biological behavior of malignant tumors. Therefore, the identification of inhibitors targeting MMP-2 could be effective in treating the disease by maintaining extracellular matrix homeostasis. In the pharmaceutical and biomedical fields, many computational tools are widely used, which improve the efficiency of the whole process to some extent. Apart from the conventional cheminformatics approaches (e.g., pharmacophore model and molecular docking), virtual screening strategies based on machine learning also have promising applications. In this study, we collected 2871 compound activity data against MMP-2 from the ChEMBL database and divided the training and test sets in a 3:1 ratio. Four machine learning algorithms were then selected to construct the classification models, and the best-performing model, i.e., the stacking-based fusion model with the highest AUC value in both training and test datasets, was used for the virtual screening of ZINC database. Next, we screened 17 potential MMP-2 inhibitors from the results predicted by the machine learning model via ADME/T analysis. The interactions between these compounds and the target protein were explored through molecular docking calculations, and the results showed that ZINC712249, ZINC4270723, and ZINC15858504 had lower binding free energies than the co-crystal ligand. To further examine the binding stability of the complexes, we performed molecular dynamics simulations and finally identified these three hits as the most promising natural products for MMP-2 inhibitors.

Estimates of genomic inbreeding and identification of candidate regions in Beijing-You chicken populations.

Runs of homozygosity (ROHs) has become an effective method for analysing inbreeding in livestock populations. Moreover, ROHs is well-suited to detect signatures of selection via ROH islands. This study aimed to investigate the occurrence and distribution of ROHs, compare the genomic inbreeding coefficients and identify the genomic regions with high ROH frequencies in different Beijing-You chicken (BY) populations, including a random conservation population (BY_R), a pedigree conservation population (BY_P), and a commercial population obtained from the market (BY_C). Among them, BY_R in 2010 and 2019 were BY_R1 and BY_R2 respectively. A total of 27 916 ROHs were identified. The average number of ROHs per individual across the three BY populations ranged from 213 (BY_P) to 161 (BY_C), and the average length of ROHs ranged from 0.432 Mb (BY_R2) to 0.451 Mb (BY_P). The highest inbreeding coefficient calculated based on ROHs (FROH ) was 0.1 in BY_P, whereas the lowest FROH was 0.0743 in BY_C. In addition, the inbreeding coefficient of BY_R2 (FROH  = 0.0798) was higher than that of BY_R1 (FROH  = 0.0579). Furthermore, the highest proportion of long ROH fragments (>4 Mb) was observed in BY_P and BY_C. This study showed the top 10 ROH islands of each population, and these ROH islands harboured 53 genes, some of which were related to limb development, body size and immune response. These findings contribute to the understanding of genetic diversity and population demography, and might help improve breeding and conservation strategies for BY populations.

Gene Co-Expression Network Analysis Reveals the Hub Genes and Key Pathways Associated with Resistance to Salmonella Enteritidis Colonization in Chicken.

Salmonella negatively impacts the poultry industry and threatens animals' and humans' health. The gastrointestinal microbiota and its metabolites can modulate the host's physiology and immune system. Recent research demonstrated the role of commensal bacteria and short-chain fatty acids (SCFAs) in developing resistance to Salmonella infection and colonization. However, the complex interactions among chicken, Salmonella, host-microbiome, and microbial metabolites remain unelucidated. Therefore, this study aimed to explore these complex interactions by identifying the driver and hub genes highly correlated with factors that confer resistance to Salmonella. Differential gene expression (DEGs) and dynamic developmental genes (DDGs) analyses and weighted gene co-expression network analysis (WGCNA) were performed using transcriptome data from the cecum of Salmonella Enteritidis-infected chicken at 7 and 21 days after infection. Furthermore, we identified the driver and hub genes associated with important traits such as the heterophil/lymphocyte (H/L) ratio, body weight post-infection, bacterial load, propionate and valerate cecal contents, and Firmicutes, Bacteroidetes, and Proteobacteria cecal relative abundance. Among the multiple genes detected in this study, EXFABP, S100A9/12, CEMIP, FKBP5, MAVS, FAM168B, HESX1, EMC6, and others were found as potential candidate gene and transcript (co-) factors for resistance to Salmonella infection. In addition, we found that the PPAR and oxidative phosphorylation (OXPHOS) metabolic pathways were also involved in the host's immune response/defense against Salmonella colonization at the earlier and later stage post-infection, respectively. This study provides a valuable resource of transcriptome profiles from chicken cecum at the earlier and later stage post-infection and mechanistic understanding of the complex interactions among chicken, Salmonella, host-microbiome, and associated metabolites.

Differential regulation of intramuscular fat and abdominal fat deposition in chickens.

BACKGROUND: Chicken intramuscular fat (IMF) content is closely related to meat quality and performance, such as tenderness and flavor. Abdominal fat (AF) in chickens is one of the main waste products at slaughter. Excessive AF reduces feed efficiency and carcass quality. RESULTS: To analyze the differential deposition of IMF and AF in chickens, gene expression profiles in the breast muscle (BM) and AF tissues of 18 animals were analyzed by differential expression analysis and weighted co-expression network analysis. The results showed that IMF deposition in BM was associated with pyruvate and citric acid metabolism through GAPDH, LDHA, GPX1, GBE1, and other genes. In contrast, AF deposition was related to acetyl CoA and glycerol metabolism through FABP1, ELOVL6, SCD, ADIPOQ, and other genes. Carbohydrate metabolism plays an essential role in IMF deposition, and fatty acid and glycerol metabolism regulate AF deposition. CONCLUSION: This study elucidated the molecular mechanism governing IMF and AF deposition through crucial genes and signaling pathways and provided a theoretical basis for producing high-quality broilers.

Integrative analysis of transcriptomics and metabolomics to reveal the melanogenesis pathway of muscle and related meat characters in Wuliangshan black-boned chickens.

BACKGROUND: Melanin is an important antioxidant in food and has been used in medicine and cosmetology. Chicken meat with high melanin content from black-boned chickens have been considered a high nutritious food with potential medicinal properties. The molecular mechanism of melanogenesis of skeletal muscle in black-boned chickens remain poorly understood. This study investigated the biological gene-metabolite associations regulating the muscle melanogenesis pathways in Wuliangshan black-boned chickens with two normal boned chicken breeds as control. RESULTS: We identified 25 differentially expressed genes and 11 transcription factors in the melanogenesis pathways. High levels of the meat flavor compounds inosine monophosphate, hypoxanthine, lysophospholipid, hydroxyoctadecadienoic acid, and nicotinamide mononucleotide were found in Wuliangshan black-boned chickens. CONCLUSION: Integrative analysis of transcriptomics and metabolomics revealed the dual physiological functions of the PDZK1 gene, involved in pigmentation and/or melanogenesis and regulating the phospholipid signaling processes in muscle of black boned chickens.

SPOP promotes ubiquitination and degradation of MyD88 to suppress the innate immune response.

As a canonical adaptor for the Toll-like receptor (TLR) family, myeloid differentiation primary response protein 88 (MyD88) has crucial roles in host defense against infection by microbial pathogens, and its dysregulation might induce autoimmune diseases. Here, we demonstrate that the chicken Cullin 3-based ubiquitin ligase adaptor Speckle-type BTB-POZ protein (chSPOP) recognizes the intermediate domain of chicken MyD88 (chMyD88) and degrades it through the proteasome pathway. Knockdown or genetic ablation of chSPOP leads to aberrant elevation of chMyD88 protein. Through this interaction, chSPOP negatively regulates NF-κB pathway activity and thus the production of IL-1ß upon LPS challenge in chicken macrophages. Furthermore, Spop-deficient mice are more susceptible to infection with Salmonella typhimurium. Collectively, these findings demonstrate MyD88 as a bona fide substrate of SPOP and uncover a mechanism by which SPOP regulates MyD88 abundance and disease susceptibility.

Comparison of genomic prediction methods for residual feed intake in broilers.

Residual feed intake (RFI) is a measure of the feed efficiency of animals. Previous studies have identified SNPs associated with RFI. The objective of this study was to compare the GBLUP model with the GA-BLUP model including previously identified associated SNPs. The nine associated SNPs were obtained from the genome-wide association study on a discovery population as preselection information. These models were analysed using ASREML software using a 5-fold cross-validation method on a validation population. With the genetic architecture (GA) matrix used, which was conducted with the nine RFI-associated SNPs, the prediction accuracy of RFI was improved compared with the original GBLUP model. The calculated optimal ω was 0.981 for RFI, which is in line with the optimal range from 0.9 to 1.0 in the gradient test. The prediction accuracy increased by 2% in the GA-BLUP model with ω being 0.981 compared with the GBLUP model. In conclusion, the GA-BLUP with the nine RFI-associated SNPs and an optimal ω can improve the prediction accuracy for a specific trait compared with GBLUP.

Discovery of Novel c-Jun N-Terminal Kinase 1 Inhibitors from Natural Products: Integrating Artificial Intelligence with Structure-Based Virtual Screening and Biological Evaluation.

c-Jun N-terminal kinase 1 (JNK1) is currently considered a critical therapeutic target for type-2 diabetes. In recent years, there has been a great interest in naturopathic molecules, and the discovery of active ingredients from natural products for specific targets has received increasing attention. Based on the above background, this research aims to combine emerging Artificial Intelligence technologies with traditional Computer-Aided Drug Design methods to find natural products with JNK1 inhibitory activity. First, we constructed three machine learning models (Support Vector Machine, Random Forest, and Artificial Neural Network) and performed model fusion based on Voting and Stacking strategies. The integrated models with better performance (AUC of 0.906 and 0.908, respectively) were then employed for the virtual screening of 4112 natural products in the ZINC database. After further drug-likeness filtering, we calculated the binding free energy of 22 screened compounds using molecular docking and performed a consensus analysis of the two methodologies. Subsequently, we identified the three most promising candidates (Lariciresinol, Tricin, and 4'-Demethylepipodophyllotoxin) according to the obtained probability values and relevant reports, while their binding characteristics were preliminarily explored by molecular dynamics simulations. Finally, we performed in vitro biological validation of these three compounds, and the results showed that Tricin exhibited an acceptable inhibitory activity against JNK1 (IC50 = 17.68 µM). This natural product can be used as a template molecule for the design of novel JNK1 inhibitors.

Integrated analysis of the methylome and transcriptome of chickens with fatty liver hemorrhagic syndrome.

BACKGROUND: DNA methylation, a biochemical modification of cytosine, has an important role in lipid metabolism. Fatty liver hemorrhagic syndrome (FLHS) is a serious disease and is tightly linked to lipid homeostasis. Herein, we compared the methylome and transcriptome of chickens with and without FLHS. RESULTS: We found genome-wide dysregulated DNA methylation pattern in which regions up- and down-stream of gene body were hypo-methylated in chickens with FLHS. A total of 4155 differentially methylated genes and 1389 differentially expressed genes were identified. Genes were focused when a negative relationship between mRNA expression and DNA methylation in promoter and gene body were detected. Based on pathway enrichment analysis, we found expression of genes related to lipogenesis and oxygenolysis (e.g., PPAR signaling pathway, fatty acid biosynthesis, and fatty acid elongation) to be up-regulated with associated down-regulated DNA methylation. In contrast, genes related to cellular junction and communication pathways (e.g., vascular smooth muscle contraction, phosphatidylinositol signaling system, and gap junction) were inhibited and with associated up-regulation of DNA methylation. CONCLUSIONS: In the current study, we provide a genome-wide scale landscape of DNA methylation and gene expression. The hepatic hypo-methylation feature has been identified with FLHS chickens. By integrated analysis, the results strongly suggest that increased lipid accumulation and hepatocyte rupture are central pathways that are regulated by DNA methylation in chickens with FLHS.

Identification of the molecular regulation of differences in lipid deposition in dedifferentiated preadipocytes from different chicken tissues.

BACKGROUND: A body distribution with high intramuscular fat and low abdominal fat is the ideal goal for broiler breeding. Preadipocytes with different origins have differences in terms of metabolism and gene expression. The transcriptome analysis performed in this study of intramuscular preadipocytes (DIMFPs) and adipose tissue-derived preadipocytes (DAFPs) aimed to explore the characteristics of lipid deposition in different chicken preadipocytes by dedifferentiation in vitro. RESULTS: Compared with DAFPs, the total lipid content in DIMFPs was reduced (P < 0.05). Moreover, 72 DEGs related to lipid metabolism were screened, which were involved in adipocyte differentiation, fatty acid transport and fatty acid synthesis, lipid stabilization, and lipolysis. Among the 72 DEGs, 19 DEGs were enriched in the PPAR signaling pathway, indicating its main contribution to the regulation of the difference in lipid deposition between DAFPs and DIMFPs. Among these 19 genes, the representative APOA1, ADIPOQ, FABP3, FABP4, FABP7, HMGCS2, LPL and RXRG genes were downregulated, but the ACSL1, FABP5, PCK2, PDPK1, PPARG, SCD, SCD5, and SLC27A6 genes were upregulated (P < 0.05 or P < 0.01) in the DIMFPs. In addition, the well-known pathways affecting lipid metabolism (MAPK, TGF-beta and calcium) and the pathways related to cell communication were enriched, which may also contribute to the regulation of lipid deposition. Finally, the regulatory network for the difference in lipid deposition between chicken DAFPs and DIMFPs was proposed based on the above information. CONCLUSIONS: Our data suggested a difference in lipid deposition between DIMFPs and DAFPs of chickens in vitro and proposed a molecular regulatory network for the difference in lipid deposition between chicken DAFPs and DIMFPs. The lipid content was significantly increased in DAFPs by the direct mediation of PPAR signaling pathways. These findings provide new insights into the regulation of tissue-specific fat deposition and the optimization of body fat distribution in broilers.

The significance of exosomal RNAs in the development, diagnosis, and treatment of pancreatic cancer.

Exosomes are single-membrane, secreted organelles with a diameter of 30-200 nm, containing diverse bioactive constituents, including DNAs, RNAs, proteins, and lipids, with prominent molecular heterogeneity. Extensive studies indicate that exosomal RNAs (e.g., microRNAs, long non-coding RNAs, and circular RNAs) can interact with many types of cancers, associated with several hallmark features like tumor growth, metastasis, and resistance to therapy. Pancreatic cancer (PaCa) is among the most lethal cancers worldwide, emerging as the seventh foremost cause of cancer-related death in both sexes. Hence, revealing the specific pathogenesis and improving the clinical diagnosis and treatment process are urgently required. As the study of exosomes has become an active area of research, the functional connections between exosomes and PaCa have been deeply investigated. Among these, exosomal RNAs seem to play a significant role in the development, diagnosis, and treatment of PaCa. Exosomal RNAs delivery ultimately modulates the various features of PaCa, and many scholars have interpreted how exosomal RNAs contribute to the proliferation, angiogenesis, migration, invasion, metastasis, immune escape, and drug resistance in PaCa. Besides, recent studies emphasize that exosomal RNAs may serve as diagnostic and prognostic biomarkers or therapeutic targets for PaCa. In this review, we will introduce these recent insights focusing on the discoveries of the relationship between exosomal RNAs and PaCa, and the potentially diagnostic and therapeutic applications of exosomes in PaCa.

Large-scale transcriptome sequencing in broiler chickens to identify candidate genes for breast muscle weight and intramuscular fat content.

BACKGROUND: In broiler production, breast muscle weight and intramuscular fat (IMF) content are important economic traits. Understanding the genetic mechanisms that underlie these traits is essential to implement effective genetic improvement programs. To date, genome-wide association studies (GWAS) and gene expression analyses have been performed to identify candidate genes for these traits. However, GWAS mainly detect associations at the DNA level, while differential expression analyses usually have low power because they are typically based on small sample sizes. To detect candidate genes for breast muscle weight and IMF contents (intramuscular fat percentage and relative content of triglycerides, cholesterol, and phospholipids), we performed association analyses based on breast muscle transcriptomic data on approximately 400 Tiannong partridge chickens at slaughter age. RESULTS: First, by performing an extensive simulation study, we evaluated the statistical properties of association analyses of gene expression levels and traits based on the linear mixed model (LMM) and three regularized linear regression models, i.e., least absolute shrinkage and selection operator (LASSO), ridge regression (RR), and elastic net (EN). The results show that LMM, LASSO and EN with tuning parameters that are determined based on the one standard error rule exhibited the lowest type I error rates. Using results from all three models, we detected 43 candidate genes with expression levels that were associated with breast muscle weight. In addition, candidate genes were detected for intramuscular fat percentage (1), triglyceride content (2), cholesterol content (1), and phospholipid content (1). Many of the identified genes have been demonstrated to play roles in the development and metabolism of skeletal muscle or adipocyte. Moreover, weighted gene co-expression network analyses revealed that many candidate genes were harbored by gene co-expression modules, which were also significantly correlated with the traits of interest. The results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that these modules are involved in muscle development and contraction, and in lipid metabolism. CONCLUSIONS: Our study provides valuable insight into the transcriptomic bases of breast muscle weight and IMF contents in Chinese indigenous yellow broilers. Our findings could be useful for the genetic improvement of these traits in broiler chickens.

Identification of QTL regions and candidate genes for growth and feed efficiency in broilers.

BACKGROUND: Feed accounts for about 70% of the total cost of poultry meat production. Residual feed intake (RFI) has become the preferred measure of feed efficiency because it is phenotypically independent of growth rate and body weight. In this study, our aim was to estimate genetic parameters and identify quantitative trait loci (QTL) for feed efficiency in 3314 purebred broilers using a genome-wide association study. Broilers were genotyped using a custom 55 K single nucleotide polymorphism (SNP) array. RESULTS: Estimates of genomic heritability for seven growth and feed efficiency traits, including body weight at 28 days of age (BW28), BW42, average daily feed intake (ADFI), RFI, and RFI adjusted for weight of abdominal fat (RFIa), ranged from 0.12 to 0.26. Eleven genome-wide significant SNPs and 15 suggestively significant SNPs were detected, of which 19 clustered around two genomic regions. A region on chromosome 16 (2.34-2.66 Mb) was associated with both BW28 and BW42, and the most significant SNP in this region, AX_101003762, accounted for 7.6% of the genetic variance of BW28. The other region, on chromosome 1 (91.27-92.43 Mb) was associated with RFI and ADFI, and contains the NSUN3 and EPHA6 as candidate genes. The most significant SNP in this region, AX_172588157, accounted for 4.4% of the genetic variance of RFI. In addition, a genomic region containing the gene AGK on chromosome 1 was found to be associated with RFIa. The NSUN3 and AGK genes were found to be differentially expressed in breast muscle, thigh muscle, and abdominal fat between male broilers with high and low RFI. CONCLUSIONS: We identified QTL regions for BW28 and BW42 (spanning 0.32 Mb) and RFI (spanning 1.16 Mb). The NSUN3, EPHA6, and AGK were identified as the most likely candidate genes for these QTL. These genes are involved in mitochondrial function and behavioral regulation. These results contribute to the identification of candidate genes and variants for growth and feed efficiency in poultry.

Identification of diverse cell populations in skeletal muscles and biomarkers for intramuscular fat of chicken by single-cell RNA sequencing.

BACKGROUND: The development of skeletal muscle is closely related to the efficiency of meat production and meat quality. Chicken skeletal muscle development depends on myogenesis and adipogenesis and occurs in two phases-hyperplasia and hypertrophy. However, cell profiles corresponding to the two-phase muscle development have yet to be determined. Single-cell RNA-sequencing (scRNA-seq) can elucidate the cell subpopulations in tissue and capture the gene expression of individual cells, which can provide new insights into the myogenesis and intramuscular adipogenesis. RESULTS: Ten cell clusters at the post-hatching developmental stage at Day 5 and seven cell clusters at the late developmental stage at Day 100 were identified in chicken breast muscles by scRNA-seq. Five myocyte-related clusters and two adipocyte clusters were identified at Day 5, and one myocyte cluster and one adipocyte cluster were identified at Day 100. The pattern of cell clustering varied between the two stages. The cell clusters showed clear boundaries at the terminal differentiation stage at Day 100; by contrast, cell differentiation was not complete at Day 5. APOA1 and COL1A1 were selected from up-regulated genes in the adipocyte cluster and found to be co-expressed with the ADIPOQ adipocyte marker gene in breast muscles by RNA in situ hybridization. CONCLUSIONS: This study is the first to describe the heterogeneity of chicken skeletal muscle at two developmental stages. The genes APOA1 and COL1A1 were identified as biomarkers for chicken intramuscular fat cells.

Genome-Wide Detection of Key Genes and Epigenetic Markers for Chicken Fatty Liver.

Chickens are one of the most important sources of meat worldwide, and the occurrence of fatty liver syndrome (FLS) is closely related to production efficiency. However, the potential mechanism of FLS remains poorly understood. An integrated analysis of data from whole-genome bisulfite sequencing and long noncoding RNA (lncRNA) sequencing was conducted. A total of 1177 differentially expressed genes (DEGs) and 1442 differentially methylated genes (DMGs) were found. There were 72% of 83 lipid- and glucose-related genes upregulated; 81% of 150 immune-related genes were downregulated in fatty livers. Part of those genes was within differentially methylated regions (DMRs). Besides, sixty-seven lncRNAs were identified differentially expressed and divided into 13 clusters based on their expression pattern. Some lipid- and glucose-related lncRNAs (e.g., LNC_006756, LNC_012355, and LNC_005024) and immune-related lncRNAs (e.g., LNC_010111, LNC_010862, and LNC_001272) were found through a co-expression network and functional annotation. From the expression and epigenetic profiles, 23 target genes (e.g., HAO1, ABCD3, and BLMH) were found to be hub genes that were regulated by both methylation and lncRNAs. We have provided comprehensive epigenetic and transcriptomic profiles on FLS in chicken, and the identification of key genes and epigenetic markers will expand our understanding of the molecular mechanism of chicken FLS.

Transcriptional insights into key genes and pathways controlling muscle lipid metabolism in broiler chickens.

BACKGROUND: Intramuscular fat (IMF) is one of the most important factors positively associated with meat quality. Triglycerides (TGs), as the main component of IMF, play an essential role in muscle lipid metabolism. This transcriptome analysis of pectoralis muscle tissue aimed to identify functional genes and biological pathways likely contributing to the extreme differences in the TG content of broiler chickens. RESULTS: The study included Jingxing-Huang broilers that were significantly different in TG content (5.81 mg/g and 2.26 mg/g, p < 0.01) and deposition of cholesterol also showed the same trend. This RNA sequencing analysis was performed on pectoralis muscle samples from the higher TG content group (HTG) and the lower TG content group (LTG) chickens. A total of 1200 differentially expressed genes (DEGs) were identified between two groups, of which 59 DEGs were related to TG and steroid metabolism. The HTG chickens overexpressed numerous genes related to adipogenesis and lipogenesis in pectoralis muscle tissue, including the key genes ADIPOQ, CD36, FABP4, FABP5, LPL, SCD, PLIN1, CIDEC and PPARG, as well as genes related to steroid biosynthesis (DHCR24, LSS, MSMO1, NSDHL and CH25H). Additionally, key pathways related to lipid storage and metabolism (the steroid biosynthesis and peroxisome proliferator activated receptor (PPAR) signaling pathway) may be the key pathways regulating differential lipid deposition between HTG group and LTG group. CONCLUSIONS: This study showed that increased TG deposition accompanying an increase in steroid synthesis in pectoralis muscle tissue. Our findings of changes in gene expression of steroid biosynthesis and PPAR signaling pathway in HTG and LTG chickens provide insight into genetic mechanisms involved in different lipid deposition patterns in pectoralis muscle tissue.

A new chicken 55K SNP genotyping array.

BACKGROUND: China has the richest local chicken breeding resources in the world and is the world's second largest producer of meat-type chickens. Development of a moderate-density SNP array for genetic analysis of chickens and breeding of meat-type chickens taking utility of those resources is urgently needed for conventional farms, breeding industry, and research areas. RESULTS: Eight representative local breeds or commercial broiler lines with 3 pools of 48 individuals within each breed/line were sequenced and supplied the major SNPs resource. There were 7.09 million - 9.41 million SNPs detected in each breed/line. After filtering using multiple criteria such as preferred incorporation of trait-related SNPs and uniformity of distribution across the genome, 52.18 K SNPs were selected in the final array. It consists of: (i) 19.22 K SNPs from the genomes of yellow-feathered, cyan-shank partridge and white-feathered chickens; (ii) 5.98 K SNPs related to economic traits from the Illumina 60 K SNP Bead Chip, which were found as significant associated SNPs with 15 traits in a Beijing-You crossed Cobb F2 resource population by genome-wide association study analysis; (iii) 7.63 K SNPs from 861 candidate genes of economic traits; (iv) the 0.94 K SNPs related to residual feed intake; and (v) 18.41 K from chicken SNPdb. The polymorphisms of 9 extra local breeds and 3 commercial lines were examined with this array, and 40 K - 47 K SNPs were polymorphic (with minor allele frequency > 0.05) in those breeds. The MDS result showed that those breeds can be clearly distinguished by this newly developed genotyping array. CONCLUSIONS: We successfully developed a 55K genotyping array by using SNPs segregated from typical local breeds and commercial lines. Compared to the existing Affy 600 K and Illumina 60 K arrays, there were 21,41 K new SNPs included on our Affy 55K array. The results of the 55K genotyping data can therefore be imputed to high-density SNPs genotyping data. The array offers a wide range of potential applications such as genomic selection breeding, GWAS of interested traits, and investigation of diversity of different chicken breeds.