Transcriptional atlas analysis from multiple tissues reveals the expression specificity patterns in beef cattle.

BACKGROUND: A comprehensive analysis of gene expression profiling across tissues can provide necessary information for an in-depth understanding of their biological functions. We performed a large-scale gene expression analysis and generated a high-resolution atlas of the transcriptome in beef cattle. RESULTS: Our transcriptome atlas was generated from 135 bovine tissues in adult beef cattle, covering 51 tissue types of major organ systems (e.g., muscular system, digestive system, immune system, reproductive system). Approximately 94.76% of sequencing reads were successfully mapped to the reference genome assembly ARS-UCD1.2. We detected a total of 60,488 transcripts, and 32% of them were not reported before. We identified 2654 housekeeping genes (HKGs) and 477 tissue-specific genes (TSGs) across tissues. Using weighted gene co-expression network analysis, we obtained 24 modules with 237 hub genes (HUBGs). Functional enrichment analysis showed that HKGs mainly maintain the basic biological activities of cells, while TSGs were involved in tissue differentiation and specific physiological processes. HKGs in bovine tissues were more conserved in terms of expression pattern as compared to TSGs and HUBGs among multiple species. Finally, we obtained a subset of tissue-specific differentially expressed genes (DEGs) between beef and dairy cattle and several functional pathways, which may be involved in production and health traits. CONCLUSIONS: We generated a large-scale gene expression atlas across the major tissues in beef cattle, providing valuable information for enhancing genome assembly and annotation. HKGs, TSGs, and HUBGs further contribute to better understanding the biology and evolution of multiple tissues in cattle. DEGs between beef and dairy cattle also fill in the knowledge gaps about differential transcriptome regulation of bovine tissues underlying economically important traits.

Comparative transcriptomic analysis reveals region-specific expression patterns in different beef cuts.

BACKGROUND: Beef cuts in different regions of the carcass have different meat quality due to their distinct physiological function. The objective of this study was to characterize the region-specific expression differences using comparative transcriptomics analysis among five representative beef cuts (tenderloin, longissimus lumborum, rump, neck, chuck). RESULTS: We obtained 15,701 expressed genes in 30 muscle samples across five regions from carcass meat. We identified a total of 80 region-specific genes (RSGs), ranging from three (identified in the rump cut) to thirty (identified in the longissimus lumborum cut), and detected 25 transcription factors (TFs) for RSGs. Using a co-expression network analysis, we detected seven region-specific modules, including three positively correlated modules and four negatively correlated modules. We finally obtained 91 candidate genes related to meat quality, and the functional enrichment analyses showed that these genes were mainly involved in muscle fiber structure (e.g., TNNI1, TNNT1), fatty acids (e.g., SCD, LPL), amino acids (ALDH2, IVD, ACADS), ion channel binding (PHPT1, SNTA1, SUMO1, CNBP), protein processing (e.g., CDC37, GAPDH, NRBP1), as well as energy production and conversion (e.g., ATP8, COX8B, NDUFB6). Moreover, four candidate genes (ALDH2, CANX, IVD, PHPT1) were validated using RT-qPCR analyses which further supported our RNA-seq results. CONCLUSIONS: Our results provide valuable insights into understanding the transcriptome regulation of meat quality in different beef cuts, and these findings may further help to improve the selection for health-beneficial meat in beef cattle.

Integration of selection signatures and multi-trait GWAS reveals polygenic genetic architecture of carcass traits in beef cattle.

Carcass merits are widely considered as economically important traits affecting beef production in the beef cattle industry. However, the genetic basis of carcass traits remains to be well understood. Here, we applied multiple methods, including the Composite of Likelihood Ratio (CLR) and Genome-wide Association Study (GWAS), to explore the selection signatures and candidate variants affecting carcass traits. We identified 11,600 selected regions overlapping with 2214 candidate genes, and most of those were enriched in binding and gene regulation. Notably, we identified 66 and 110 potential variants significantly associated with carcass traits using single-trait and multi-traits analyses, respectively. By integrating selection signatures with single and multi-traits associations, we identified 12 and 27 putative genes, respectively. Several highly conserved missense variants were identified in OR5M13D, NCAPG, and TEX2. Our study supported polygenic genetic architecture of carcass traits and provided novel insights into the genetic basis of complex traits in beef cattle.

Genomic sequencing analysis reveals copy number variations and their associations with economically important traits in beef cattle.

Copy number variation (CNV) represents a major source of genetic variation, which may have potentially large effects, including alternating gene regulation and dosage, as well as contributing to gene expression and risk for normal phenotypic variability. We carried out a comprehensive analysis of CNV based on whole genome sequencing in Chinese Simmental beef cattle. Totally, we found 9313 deletion and 234 duplication events, covering 147.5 Mb autosomal regions. Within them, 257 deletion events of high frequency overlapped with 193 known RefGenes. Among these genes, we observed several genes were related to economically important traits, like residual feed intake, immune responding, pregnancy rate and muscle differentiation. Using a locus-based analysis, we identified 11 deletions and 1 duplication, which were significantly associated with three traits including carcass weight, tenderloin and longissimus muscle area. Our sequencing-based study provided important insights into investigating the association of CNVs with important traits in beef cattle.

Cis-eQTL Analysis and Functional Validation of Candidate Genes for Carcass Yield Traits in Beef Cattle.

Carcass yield traits are of considerable economic importance for farm animals, which act as a major contributor to the world's food supply. Genome-wide association studies (GWASs) have identified many genetic variants associated with carcass yield traits in beef cattle. However, their functions are not effectively illustrated. In this study, we performed an integrative analysis of gene-based GWAS with expression quantitative trait locus (eQTL) analysis to detect candidate genes for carcass yield traits and validate their effects on bovine skeletal muscle satellite cells (BSCs). The gene-based GWAS and cis-eQTL analysis revealed 1780 GWAS and 1538 cis-expression genes. Among them, we identified 153 shared genes that may play important roles in carcass yield traits. Notably, the identified cis-eQTLs of PON3 and PRIM2 were significantly (p < 0.001) enriched in previous GWAS loci for carcass traits. Furthermore, overexpression of PON3 and PRIM2 promoted the BSCs' proliferation, increased the expression of MYOD and downregulated the expression of MYOG, which indicated that these genes may inhibit myogenic differentiation. In contrast, PON3 and PRIM2 were significantly downregulated during the differentiation of BSCs. These findings suggested that PON3 and PRIM2 may promote the proliferation of BSCs and inhibit them in the pre-differentiation stage. Our results further contribute to the understanding of the molecular mechanisms of carcass yield traits in beef cattle.

Runs of homozygosity analysis reveals consensus homozygous regions affecting production traits in Chinese Simmental beef cattle.

BACKGROUND: Genomic regions with a high frequency of runs of homozygosity (ROH) are related to important traits in farm animals. We carried out a comprehensive analysis of ROH and evaluated their association with production traits using the BovineHD (770 K) SNP array in Chinese Simmental beef cattle. RESULTS: We detected a total of 116,953 homozygous segments with 2.47Gb across the genome in the studied population. The average number of ROH per individual was 99.03 and the average length was 117.29 Mb. Notably, we detected 42 regions with a frequency of more than 0.2. We obtained 17 candidate genes related to body size, meat quality, and reproductive traits. Furthermore, using Fisher's exact test, we found 101 regions were associated with production traits by comparing high groups with low groups in terms of production traits. Of those, we identified several significant regions for production traits (P < 0.05) by association analysis, within which candidate genes including ECT2, GABRA4, and GABRB1 have been previously reported for those traits in beef cattle. CONCLUSIONS: Our study explored ROH patterns and their potential associations with production traits in beef cattle. These results may help to better understand the association between production traits and genome homozygosity and offer valuable insights into managing inbreeding by designing reasonable breeding programs in farm animals.

Research Progress and Applications of Bovine Genome in the Tribe Bovini.

Various bovine species have been domesticated and bred for thousands of years, and they provide adequate animal-derived products, including meat, milk, and leather, to meet human requirements. Despite the review studies on economic traits in cattle, the genetic basis of traits has only been partially explained by phenotype and pedigree breeding methods, due to the complexity of genomic regulation during animal development and growth. With the advent of next-generation sequencing technology, genomics projects, such as the 1000 Bull Genomes Project, Functional Annotation of Animal Genomes project, and Bovine Pangenome Consortium, have advanced bovine genomic research. These large-scale genomics projects gave us a comprehensive concept, technology, and public resources. In this review, we summarize the genomics research progress of the main bovine species during the past decade, including cattle (Bos taurus), yak (Bos grunniens), water buffalo (Bubalus bubalis), zebu (Bos indicus), and gayal (Bos frontalis). We mainly discuss the development of genome sequencing and functional annotation, focusing on how genomic analysis reveals genetic variation and its impact on phenotypes in several bovine species.

Population Structure and Selection Signal Analysis of Nanyang Cattle Based on Whole-Genome Sequencing Data.

With a rich breeding history, Nanyang cattle (NY cattle) have undergone extensive natural and artificial selection, resulting in distinctive traits such as high fertility, excellent meat quality, and disease resistance. This makes them an ideal model for studying the mechanisms of environmental adaptability. To assess the population structure and genetic diversity of NY cattle, we performed whole-genome resequencing on 30 individuals. These data were then compared with published whole-genome resequencing data from 432 cattle globally. The results indicate that the genetic structure of NY cattle is significantly different from European commercial breeds and is more similar to North-Central Chinese breeds. Furthermore, among all breeds, NY cattle exhibit the highest genetic diversity and the lowest population inbreeding levels. A genome-wide selection signal analysis of NY cattle and European commercial breeds using Fst, θπ-ratio, and θπ methods revealed significant selection signals in genes associated with reproductive performance and immunity. Our functional annotation analysis suggests that these genes may be responsible for reproduction (MAP2K2, PGR, and GSE1), immune response (NCOA2, HSF1, and PAX5), and olfaction (TAS1R3). We provide a comprehensive overview of sequence variations in the NY cattle genome, revealing insights into the population structure and genetic diversity of NY cattle. Additionally, we identify candidate genes associated with important economic traits, offering valuable references for future conservation and breeding efforts of NY cattle.

Comparative Transcriptomic Analysis Reveals Diverse Expression Pattern Underlying Fatty Acid Composition among Different Beef Cuts.

Beef is an important dietary source of quality animal proteins and amino acids in human nutrition. The fatty acid composition is one of the indispensable indicators affecting nutritional value of beef. However, a comprehensive understanding of the expression changes underlying fatty acid composition in representative beef cuts is needed in cattle. This study aimed to characterize the dynamics of fatty acid composition using comparative transcriptomic analysis in five different type of beef cuts. We identified 7545 differentially expressed genes (DEGs) among 10 pair-wise comparisons. Co-expression gene network analysis identified two modules, which were significantly correlated with 2 and 20 fatty acid composition, respectively. We also identified 38 candidate genes, and functional enrichment showed that these genes were involved in fatty acid biosynthetic process and degradation, PPAR, and AMPK signaling pathway. Moreover, we observed a cluster of DEGs (e.g., SCD, LPL, FABP3, and PPARD) which were involved in the regulation of lipid metabolism and adipocyte differentiation. Our results provide some valuable insights into understanding the transcriptome regulation of candidate genes on fatty acid composition of beef cuts, and our findings may facilitate the designs of genetic selection program for beneficial fatty acid composition in beef cattle.

A draft genome of Drung cattle reveals clues to its chromosomal fusion and environmental adaptation.

Drung cattle (Bos frontalis) have 58 chromosomes, differing from the Bos taurus 2n = 60 karyotype. To date, its origin and evolution history have not been proven conclusively, and the mechanisms of chromosome fusion and environmental adaptation have not been clearly elucidated. Here, we assembled a high integrity and good contiguity genome of Drung cattle with 13.7-fold contig N50 and 4.1-fold scaffold N50 improvements over the recently published Indian mithun assembly, respectively. Speciation time estimation and phylogenetic analysis showed that Drung cattle diverged from Bos taurus into an independent evolutionary clade. Sequence evidence of centromere regions provides clues to the breakpoints in BTA2 and BTA28 centromere satellites. We furthermore integrated a circulation and contraction-related biological process involving 43 evolutionary genes that participated in pathways associated with the evolution of the cardiovascular system. These findings may have important implications for understanding the molecular mechanisms of chromosome fusion, alpine valleys adaptability and cardiovascular function.

Comparative Transcriptome Analysis of Gayal (Bos frontalis), Yak (Bos grunniens), and Cattle (Bos taurus) Reveal the High-Altitude Adaptation.

Gayal and yak are well adapted to the local high-altitude environments, yet the transcriptional regulation difference of the plateau environment among them remains obscure. Herein, cross-tissue and cross-species comparative transcriptome analysis were performed for the six hypoxia-sensitive tissues from gayal, yak, and cattle. Gene expression profiles for all single-copy orthologous genes showed tissue-specific expression patterns. By differential expression analysis, we identified 3020 and 1995 differentially expressed genes (DEGs) in at least one tissue of gayal vs. cattle and yak vs. cattle, respectively. Notably, we found that the adaptability of the gayal to the alpine canyon environment is highly similar to the yak living in the Qinghai-Tibet Plateau, such as promoting red blood cell development, angiogenesis, reducing blood coagulation, immune system activation, and energy metabolism shifts from fatty acid ß-oxidation to glycolysis. By further analyzing the common and unique DEGs in the six tissues, we also found that numerous expression regulatory genes related to these functions are unique in the gayal and yak, which may play important roles in adapting to the corresponding high-altitude environment. Combined with WGCNA analysis, we found UQCRC1, COX5A are the shared differentially expression hub genes related to the energy supply of myocardial contraction in the heart-related modules of gayal and yak, and CAPS is a shared differentially hub gene among the hub genes of the lung-related module, which is related to pulmonary artery smooth muscle contraction. Additionally, EDN3 is the unique differentially expression hub gene related to the tracheal epithelium and pulmonary vasoconstriction in the lung of gayal. CHRM2 is a unique differentially expression hub gene that was identified in the heart of yak, which has an important role in the autonomous regulation of the heart. These results provide a basis for further understanding the complex transcriptome expression pattern and the regulatory mechanism of high-altitude domestication of gayal and yak.

Identification of Candidate Variants Associated With Bone Weight Using Whole Genome Sequence in Beef Cattle.

Bone weight is critical to affect body conformation and stature in cattle. In this study, we conducted a genome-wide association study for bone weight in Chinese Simmental beef cattle based on the imputed sequence variants. We identified 364 variants associated with bone weight, while 350 of them were not included in the Illumina BovineHD SNP array, and several candidate genes and GO terms were captured to be associated with bone weight. Remarkably, we identified four potential variants in a candidate region on BTA6 using Bayesian fine-mapping. Several important candidate genes were captured, including LAP3, MED28, NCAPG, LCORL, SLIT2, and IBSP, which have been previously reported to be associated with carcass traits, body measurements, and growth traits. Notably, we found that the transcription factors related to MED28 and LCORL showed high conservation across multiple species. Our findings provide some valuable information for understanding the genetic basis of body stature in beef cattle.

Genome-Wide Assessment of Runs of Homozygosity in Chinese Wagyu Beef Cattle.

Runs of homozygosity (ROH) are continuous homozygous regions that generally exist in the DNA sequence of diploid organisms. Identifications of ROH leading to reduction in performance can provide valuable insight into the genetic architecture of complex traits. Here, we evaluated genome-wide patterns of homozygosity and their association with important traits in Chinese Wagyu beef cattle. We identified a total of 29,271 ROH segments from 462 animals. Within each animal, an average number of ROH was 63.36 while an average length was 62.19 Mb. To evaluate the enrichment of ROH across genomes, we initially identified 280 ROH regions by merging ROH events across all individuals. Of these, nine regions containing 154 candidate genes, were significantly associated with six traits (body height, chest circumference, fat coverage, backfat thickness, ribeye area, and carcass length; p < 0.01). Moreover, we found 26 consensus ROH regions with frequencies exceeding 10%, and several regions overlapped with QTLs, which are associated with body weight, calving ease, and stillbirth. Among them, we observed 41 candidate genes, including BCKDHB, MAB21L1, SLC2A13, FGFR3, FGFRL1, CPLX1, CTNNA1, CORT, CTNNBIP1, and NMNAT1, which have been previously reported to be related to body conformation, meat quality, susceptibility, and reproductive traits. In summary, we assessed genome-wide autozygosity patterns and inbreeding levels in Chinese Wagyu beef cattle. Our study identified many candidate regions and genes overlapped with ROH for several important traits, which could be unitized to assist the design of a selection mating strategy in beef cattle.

Selection and effectiveness of informative SNPs for paternity in Chinese Simmental cattle based on a high-density SNP array.

Incorrect paternity assignment in cattle can significantly influence the accuracy of genetic evaluation. Recent advances in high-throughput technology have facilitated the identification of single nucleotide polymorphism (SNP) markers and their applications for filiation and individual identification. We genotyped 1074 bulls from a reference population of Chinese Simmental cattle for genomic selection using a BovineSNP770K BeadChip. Among them, a total of 136 bulls were randomly selected to design a suitable low-density SNP panel for paternity testing in Simmental cattle. Our results showed that 50 SNPs were determined to be the most informative markers in parental testing, with an accuracy of 99.89% for CPE (cumulative probability of exclusion) in the unknown female parent case. The 50 highly informative SNP markers were distributed across 25 chromosomes, and the mean intermarker distance per chromosome was 26.72 Mb. The average minor allele frequency (MAF), expected heterozygosity (HE), and polymorphic information content (PIC) values were 0.3748, 0.4998, and 0.4818, respectively. Finally, the 50 identified SNPs were used to estimate paternity for the remaining 938 of 1074 bulls from 23 farms. Our results revealed that 76.75% of the 938 bulls were assigned parentage to the pedigree sires with 95% confidence, and the rate of pedigree record mistakes ranged from 9.52%-39.29% in different herds. Our study is the first attempt to provide valuable insights into the extraction of informative markers through the application of high-density SNP chips for paternity testing in Chinese Simmental cattle.