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1.
Sci Rep ; 14(1): 13682, 2024 06 13.
Article in English | MEDLINE | ID: mdl-38871745

ABSTRACT

Feed cost represents a major economic determinant within cattle production, amounting to an estimated 75% of the total variable costs. Consequently, comprehensive approaches such as optimizing feed utilization through alternative feed sources, alongside the selection of feed-efficient animals, are of great significance. Here, we investigate the effect of two diets, traditional corn-grain fed and alternative by-product based, on 14 phenotypes related to feed, methane emission and production efficiency and on multi-tissue transcriptomics data from liver, muscle, and rumen wall, derived from 52 Nellore bulls, 26 on each diet. To this end, diets were contrasted at the level of phenotype, gene expression, and gene-phenotype network connectivity. As regards the phenotypic level, at a P value < 0.05, significant differences were found in favour of the alternative diet for average daily weight gain at finishing, dry matter intake at finishing, methane emission, carcass yield and subcutaneous fat thickness at the rib-eye muscle area. In terms of the transcriptional level of the 14,776 genes expressed across the examined tissues, we found 487, 484, and 499 genes differentially expressed due to diet in liver, muscle, and rumen, respectively (P value < 0.01). To explore differentially connected phenotypes across both diet-based networks, we focused on the phenotypes with the largest change in average number of connections within diets and tissues, namely methane emission and carcass yield, highlighting, in particular, gene expression changes involving SREBF2, and revealing the largest differential connectivity in rumen and muscle, respectively. Similarly, from examination of differentially connected genes across diets, the top-ranked most differentially connected regulators within each tissue were MEOX1, PTTG1, and BASP1 in liver, muscle, and rumen, respectively. Changes in gene co-expression patterns suggest activation or suppression of specific biological processes and pathways in response to dietary interventions, consequently impacting the phenotype. The identification of genes that respond differently to diets and their associated phenotypic effects serves as a crucial stepping stone for further investigations, aiming to build upon our discoveries. Ultimately, such advancements hold the promise of improving animal welfare, productivity, and sustainability in livestock farming.


Subject(s)
Animal Feed , Diet , Liver , Rumen , Animals , Cattle/genetics , Liver/metabolism , Rumen/metabolism , Animal Feed/analysis , Diet/veterinary , Transcriptome , Male , Muscle, Skeletal/metabolism , Phenotype , Gene Regulatory Networks , Gene Expression Profiling
2.
Sci Rep ; 14(1): 10094, 2024 05 02.
Article in English | MEDLINE | ID: mdl-38698200

ABSTRACT

Intramuscular fat (IMF) and backfat thickness (BFT) are critical economic traits impacting meat quality. However, the genetic variants controlling these traits need to be better understood. To advance knowledge in this area, we integrated RNA-seq and single nucleotide polymorphisms (SNPs) identified in genomic and transcriptomic data to generate a linkage disequilibrium filtered panel of 553,581 variants. Expression quantitative trait loci (eQTL) analysis revealed 36,916 cis-eQTLs and 14,408 trans-eQTLs. Association analysis resulted in three eQTLs associated with BFT and 24 with IMF. Functional enrichment analysis of genes regulated by these 27 eQTLs revealed noteworthy pathways that can play a fundamental role in lipid metabolism and fat deposition, such as immune response, cytoskeleton remodeling, iron transport, and phospholipid metabolism. We next used ATAC-Seq assay to identify and overlap eQTL and open chromatin regions. Six eQTLs were in regulatory regions, four in predicted insulators and possible CCCTC-binding factor DNA binding sites, one in an active enhancer region, and the last in a low signal region. Our results provided novel insights into the transcriptional regulation of IMF and BFT, unraveling putative regulatory variants.


Subject(s)
Chromatin , Polymorphism, Single Nucleotide , Quantitative Trait Loci , Animals , Cattle , Chromatin/genetics , Chromatin/metabolism , Adipose Tissue/metabolism , Mutation , Linkage Disequilibrium , Genome-Wide Association Study , Gene Expression Regulation , Lipid Metabolism/genetics
3.
Parasit Vectors ; 17(1): 102, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38429820

ABSTRACT

BACKGROUND: The integration of molecular data from hosts, parasites, and microbiota can enhance our understanding of the complex biological interactions underlying the resistance of hosts to parasites. Haemonchus contortus, the predominant sheep gastrointestinal parasite species in the tropics, causes significant production and economic losses, which are further compounded by the diminishing efficiency of chemical control owing to anthelmintic resistance. Knowledge of how the host responds to infection and how the parasite, in combination with microbiota, modulates host immunity can guide selection decisions to breed animals with improved parasite resistance. This understanding will help refine management practices and advance the development of new therapeutics for long-term helminth control. METHODS: Eggs per gram (EPG) of feces were obtained from Morada Nova sheep subjected to two artificial infections with H. contortus and used as a proxy to select animals with high resistance or susceptibility for transcriptome sequencing (RNA-seq) of the abomasum and 50 K single-nucleotide genotyping. Additionally, RNA-seq data for H. contortus were generated, and amplicon sequence variants (ASV) were obtained using polymerase chain reaction amplification and sequencing of bacterial and archaeal 16S ribosomal RNA genes from sheep feces and rumen content. RESULTS: The heritability estimate for EPG was 0.12. GAST, GNLY, IL13, MGRN1, FGF14, and RORC genes and transcripts were differentially expressed between resistant and susceptible animals. A genome-wide association study identified regions on chromosomes 2 and 11 that harbor candidate genes for resistance, immune response, body weight, and adaptation. Trans-expression quantitative trait loci were found between significant variants and differentially expressed transcripts. Functional co-expression modules based on sheep genes and ASVs correlated with resistance to H. contortus, showing enrichment in pathways of response to bacteria, immune and inflammatory responses, and hub features of the Christensenellaceae, Bacteroides, and Methanobrevibacter genera; Prevotellaceae family; and Verrucomicrobiota phylum. In H. contortus, some mitochondrial, collagen-, and cuticle-related genes were expressed only in parasites isolated from susceptible sheep. CONCLUSIONS: The present study identified chromosome regions, genes, transcripts, and pathways involved in the elaborate interactions between the sheep host, its gastrointestinal microbiota, and the H. contortus parasite. These findings will assist in the development of animal selection strategies for parasite resistance and interdisciplinary approaches to control H. contortus infection in sheep.


Subject(s)
Haemonchiasis , Haemonchus , Microbiota , Parasites , Sheep Diseases , Sheep/genetics , Animals , Parasites/genetics , Genome-Wide Association Study , Multiomics , Feces/parasitology , Sheep Diseases/parasitology , Haemonchiasis/parasitology , Parasite Egg Count
4.
Mamm Genome ; 35(2): 186-200, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38480585

ABSTRACT

Approximately 80% of the world's cattle are raised in regions with a high risk of tick-borne diseases, resulting in significant economic losses due to parasitism by Rhipicephalus (Boophilus) microplus. However, the lack of a systemic biology approach hampers a comprehensive understanding of tick-host interactions that mediate tick resistance phenotypes. Here, we conducted a genome-wide association study (GWAS) of 2933 Braford cattle and found 340 single-nucleotide polymorphisms (SNPs) associated with tick counts. Gene expression analyses were performed on skin samples obtained from previously tick-exposed heifers with extremely high or low estimated breeding values for R. microplus counts. Evaluations were performed both before and after artificial infestation with ticks. Differentially expressed genes were found within 1-Mb windows centered at significant SNPs from GWAS. A total of 330 genes were related to the breakdown of homeostasis that was induced by larval attachment to bovine skin. Enrichment analysis pointed to a key role of proteolysis and signal transduction via JAK/STAT, NFKB and WNT/beta catenin signaling pathways. Integrative analysis on matrixEQTL revealed two cis-eQTLs and four significant SNPs in the genes peptidyl arginine deiminase type IV (PADI4) and LOC11449251. The integration of genomic data from QTL maps and transcriptome analyses has identified a set of twelve key genes that show significant associations with tick loads. These genes could be key candidates to improve the accuracy of genomic predictions for tick resistance in Braford cattle.


Subject(s)
Disease Resistance , Genome-Wide Association Study , Polymorphism, Single Nucleotide , Rhipicephalus , Tick Infestations , Animals , Cattle , Rhipicephalus/genetics , Rhipicephalus/physiology , Tick Infestations/veterinary , Tick Infestations/genetics , Tick Infestations/parasitology , Tick Infestations/immunology , Disease Resistance/genetics , Systems Biology , Cattle Diseases/genetics , Cattle Diseases/immunology , Cattle Diseases/parasitology , Quantitative Trait Loci , Female , Host-Parasite Interactions/genetics , Host-Parasite Interactions/immunology
5.
Sci Rep ; 13(1): 18001, 2023 10 21.
Article in English | MEDLINE | ID: mdl-37865691

ABSTRACT

The objectives of this study were twofold: (1) to identify potential differences in the ruminal and fecal metabolite profiles of Nelore bulls under different nutritional interventions; and (2) to identify metabolites associated with cattle sustainability related-traits. We used different nutritional interventions in the feedlot: conventional (Conv; n = 26), and by-product (ByPr, n = 26). Thirty-eight ruminal fluid and 27 fecal metabolites were significantly different (P < 0.05) between the ByPr and Conv groups. Individual dry matter intake (DMI), residual feed intake (RFI), observed water intake (OWI), predicted water intake (WI), and residual water intake (RWI) phenotypes were lower (P < 0.05) in the Conv group, while the ByPr group exhibited lower methane emission (ME) (P < 0.05). Ruminal fluid dimethylamine was significantly associated (P < 0.05) with DMI, RFI, FE (feed efficiency), OWI and WI. Aspartate was associated (P < 0.05) with DMI, RFI, FE and WI. Fecal C22:1n9 was significantly associated with OWI and RWI (P < 0.05). Fatty acid C14:0 and hypoxanthine were significantly associated with DMI and RFI (P < 0.05). The results demonstrated that different nutritional interventions alter ruminal and fecal metabolites and provided new insights into the relationship of these metabolites with feed efficiency and water intake traits in Nelore bulls.


Subject(s)
Drinking , Feeding Behavior , Cattle , Animals , Male , Methane/metabolism , Diet/veterinary , Animal Feed/analysis , Eating , Feces
6.
Trop Anim Health Prod ; 55(5): 302, 2023 Sep 19.
Article in English | MEDLINE | ID: mdl-37726409

ABSTRACT

The study was conducted with the objective of estimating genetic and phenotypic parameters for tick (CRM) and Babesia bigemina (IBBi), Babesia bovis (IBBo), and Anaplasma marginale (IAM) burden in Angus female breed in Brazil. The sample group was composed of Angus females raised in herds located in a region of endemic instability for cattle tick fever in the state of Rio Grande Sul (RS), Brazil. The variance components were estimated using Bayesian inference and Gibbs sampling algorithm, considering a multi-trait animal model. Heritability estimates showed values of low magnitude, ranging from 0.03 (IBBo) to 0.16 (CRM), while repeatability estimates ranged between 0.07 (IBBo) and 0.21 (CRM). Regarding the genetic correlation estimates, the values showed low (-0.01 for IBBo × IAM) to moderate (0.55 between IBBi × IAM) magnitudes. The results indicate that it is possible to use tick count and hemoparasite infection levels as selection criteria, with small genetic gains.


Subject(s)
Anaplasma marginale , Babesia , Babesiosis , Female , Animals , Bayes Theorem , Algorithms , Babesia/genetics , Babesiosis/epidemiology
7.
Funct Integr Genomics ; 23(1): 73, 2023 Mar 03.
Article in English | MEDLINE | ID: mdl-36867299

ABSTRACT

Pork is of great importance in world trade and represents the largest source of fatty acids in the human diet. Lipid sources such as soybean oil (SOY), canola (CO), and fish oil (FO) are used in pig diets and influence blood parameters and the ratio of deposited fatty acids. In this study, the main objective was to evaluate changes in gene expression in porcine skeletal muscle tissue resulting from the dietary oil sources and to identify metabolic pathways and biological process networks through RNA-Seq. The addition of FO in the diet of pigs led to intramuscular lipid with a higher FA profile composition of C20:5 n-3, C22:6 n-3, and SFA (C16:0 and C18:0). Blood parameters for the FO group showed lower cholesterol and HDL content compared with CO and SOY groups. Skeletal muscle transcriptome analyses revealed 65 differentially expressed genes (DEG, FDR 10%) between CO vs SOY, and 32 DEG for CO vs FO, and 531 DEG for SOY vs FO comparison. Several genes, including AZGP1, PDE3B, APOE, PLIN1, and LIPS, were found to be down-regulated in the diet of the SOY group compared to the FO group. The enrichment analysis revealed DEG involved in lipid metabolism, metabolic diseases, and inflammation between the oil groups, with specific gene functions in each group and altered blood parameters. The results provide mechanisms to help us understand the behavior of genes according to fatty acids.


Subject(s)
Gene Expression Profiling , Transcriptome , Humans , Animals , Male , Swine , Fatty Acids , Inflammation , Muscle, Skeletal , Soybean Oil
8.
BMC Genomics ; 24(1): 91, 2023 Feb 28.
Article in English | MEDLINE | ID: mdl-36855067

ABSTRACT

BACKGROUND: The high similarity in anatomical and neurophysiological processes between pigs and humans make pigs an excellent model for metabolic diseases and neurological disorders. Lipids are essential for brain structure and function, and the polyunsaturated fatty acids (PUFA) have anti-inflammatory and positive effects against cognitive dysfunction in neurodegenerative diseases. Nutrigenomics studies involving pigs and fatty acids (FA) may help us in better understanding important biological processes. In this study, the main goal was to evaluate the effect of different levels of dietary soybean oil on the lipid profile and transcriptome in pigs' brain tissue. RESULTS: Thirty-six male Large White pigs were used in a 98-day study using two experimental diets corn-soybean meal diet containing 1.5% soybean oil (SOY1.5) and corn-soybean meal diet containing 3.0% soybean oil (SOY3.0). No differences were found for the brain total lipid content and FA profile between the different levels of soybean oil. For differential expression analysis, using the DESeq2 statistical package, a total of 34 differentially expressed genes (DEG, FDR-corrected p-value < 0.05) were identified. Of these 34 DEG, 25 are known-genes, of which 11 were up-regulated (log2 fold change ranging from + 0.25 to + 2.93) and 14 were down-regulated (log2 fold change ranging from - 3.43 to -0.36) for the SOY1.5 group compared to SOY3.0. For the functional enrichment analysis performed using MetaCore with the 34 DEG, four pathway maps were identified (p-value < 0.05), related to the ALOX15B (log2 fold change - 1.489), CALB1 (log2 fold change - 3.431) and CAST (log2 fold change + 0.421) genes. A "calcium transport" network (p-value = 2.303e-2), related to the CAST and CALB1 genes, was also identified. CONCLUSION: The results found in this study contribute to understanding the pathways and networks associated with processes involved in intracellular calcium, lipid metabolism, and oxidative processes in the brain tissue. Moreover, these results may help a better comprehension of the modulating effects of soybean oil and its FA composition on processes and diseases affecting the brain tissue.


Subject(s)
Soybean Oil , Transcriptome , Animals , Male , Brain , Calcium , Diet/veterinary , Fatty Acids , Soybean Oil/pharmacology , Swine
9.
Front Genet ; 14: 1053021, 2023.
Article in English | MEDLINE | ID: mdl-36816031

ABSTRACT

Pigs (Sus scrofa) are an animal model for metabolic diseases in humans. Pork is an important source of fatty acids (FAs) in the human diet, as it is one of the most consumed meats worldwide. The effects of dietary inclusion of oils such as canola, fish, and soybean oils on pig gene expression are mostly unknown. Our objective was to evaluate FA composition, identify changes in gene expression in the liver of male pigs fed diets enriched with different FA profiles, and identify impacted metabolic pathways and gene networks to enlighten the biological mechanisms' variation. Large White male pigs were randomly allocated to one of three diets with 18 pigs in each; all diets comprised a base of corn and soybean meal to which either 3% of soybean oil (SOY), 3% canola oil (CO), or 3% fish oil (FO) was added for a 98-day trial during the growing and finishing phases. RNA sequencing was performed on the liver samples of each animal by Illumina technology for differential gene expression analyses, using the R package DESeq2. The diets modified the FA profile, mainly in relation to polyunsaturated and saturated FAs. Comparing SOY vs. FO, 143 differentially expressed genes (DEGs) were identified as being associated with metabolism, metabolic and neurodegenerative disease pathways, inflammatory processes, and immune response networks. Comparing CO vs. SOY, 148 DEGs were identified, with pathways related to FA oxidation, regulation of lipid metabolism, and metabolic and neurodegenerative diseases. Our results help explain the behavior of genes with differential expression in metabolic pathways resulting from feeding different types of oils in pig diets.

10.
Biochem Biophys Rep ; 33: 101420, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36654922

ABSTRACT

Epigenetic repression has been linked to the regulation of different cell states. In this study, we focus on the influence of this repression, mainly by H3K27me3, over gene expression in muscle cells, which may affect mineral content, a phenotype that is relevant to muscle function and beef quality. Based on the inverse relationship between H3K27me3 and gene expression (i.e., epigenetic repression) and on contrasting sample groups, we computationally predicted regulatory genes that affect muscle mineral content. To this end, we applied the TRIAGE predictive method followed by a rank product analysis. This methodology can predict regulatory genes that might be affected by repressive epigenetic regulation related to mineral concentration. Annotation of orthologous genes, between human and bovine, enabled our investigation of gene expression in the Longissimus thoracis muscle of Bos indicus cattle. The animals under study had a contrasting mineral content in their muscle cells. We identified candidate regulatory genes influenced by repressive epigenetic mechanisms, linking histone modification to mineral content in beef samples. The discovered candidate genes take part in multiple biological pathways, i.e., impulse transmission, cell signalling, immunological, and developmental pathways. Some of these genes were previously associated with mineral content or regulatory mechanisms. Our findings indicate that epigenetic repression can partially explain the gene expression profiles observed in muscle samples with contrasting mineral content through the candidate regulators here identified.

11.
Mamm Genome ; 34(1): 90-103, 2023 03.
Article in English | MEDLINE | ID: mdl-36463529

ABSTRACT

Feed-efficient cattle selection is among the most leading solutions to reduce cost for beef cattle production. However, technical difficulties in measuring feed efficiency traits had limited the application in livestock. Here, we performed a Bivariate Genome-Wide Association Study (Bi-GWAS) and presented candidate biological mechanisms underlying the association between feed efficiency and meat quality traits in a half-sibling design with 353 Nelore steers derived from 34 unrelated sires. A total of 13 Quantitative Trait Loci (QTL) were found explaining part of the phenotypic variations. An important transcription factor of adipogenesis in cattle, the TAL1 (rs133408775) gene located on BTA3 was associated with intramuscular fat and average daily gain (IMF-ADG), and a region located on BTA20, close to CD180 and MAST4 genes, both related to fat accumulation. We observed a low positive genetic correlation between IMF-ADG (r = 0.30 ± 0.0686), indicating that it may respond to selection in the same direction. Our findings contributed to clarifying the pleiotropic modulation of the complex traits, indicating new QTLs for bovine genetic improvement.


Subject(s)
Genome-Wide Association Study , Quantitative Trait Loci , Cattle , Animals , Genome-Wide Association Study/veterinary , Phenotype , Gene Expression Regulation , Meat , Polymorphism, Single Nucleotide
12.
Front Microbiol ; 14: 1282851, 2023.
Article in English | MEDLINE | ID: mdl-38163076

ABSTRACT

Background: Ruminants harbor a complex microbial community within their gastrointestinal tract, which plays major roles in their health and physiology. Brazil is one of the largest producers of beef in the world and more than 90% of the beef cattle herds are composed of pure and crossbred Nelore (Bos indicus). Despite its importance to the Brazilian economy and human feeding, few studies have characterized the Nelore microbiome. Therefore, using shotgun metagenomics, we investigated the impact of diet on the composition and functionality of the Nelore microbiome, and explored the associations between specific microbial taxa and their functionality with feed efficiency and methane emission. Results: The ruminal microbiome exhibited significantly higher microbial diversity, distinctive taxonomic profile and variations in microbial functionality compared to the fecal microbiome, highlighting the distinct contributions of the microbiomes of these environments. Animals subjected to different dietary treatments exhibited significant differences in their microbiomes' archaeal diversity and in the abundance of 89 genera, as well as in the functions associated with the metabolism of components of each diet. Moreover, depending on the diet, feed-efficient animals and low methane emitters displayed higher microbial diversity in their fecal microbiome. Multiple genera were associated with an increase or decrease of the phenotypes. Upon analyzing the functions attributed to these taxa, we observed significant differences on the ruminal taxa associated with feed efficient and inefficient cattle. The ruminal taxa that characterized feed efficient cattle stood out for having significantly more functions related to carbohydrate metabolism, such as monosaccharides, di-/oligosaccharides and amino acids. The taxa associated with methane emission had functions associated with methanogenesis and the production of substrates that may influence methane production, such as hydrogen and formate. Conclusion: Our findings highlight the significant role of diet in shaping Nelore microbiomes and how its composition and functionality may affect production traits such as feed efficiency and methane emission. These insights provide valuable support for the implementation of novel feeding and biotechnological strategies.

13.
Genes (Basel) ; 13(12)2022 12 11.
Article in English | MEDLINE | ID: mdl-36553605

ABSTRACT

Traditional transcriptomics approaches have been used to identify candidate genes affecting economically important livestock traits. Regulatory variants affecting these traits, however, remain under covered. Genomic regions showing allele-specific expression (ASE) are under the effect of cis-regulatory variants, being useful for improving the accuracy of genomic selection models. Taking advantage of the better of these two methods, we investigated single nucleotide polymorphisms (SNPs) in regions showing differential ASE (DASE SNPs) between contrasting groups for beef quality traits. For these analyses, we used RNA sequencing data, imputed genotypes and genomic estimated breeding values of muscle-related traits from 190 Nelore (Bos indicus) steers. We selected 40 contrasting unrelated samples for the analysis (N = 20 animals per contrasting group) and used a beta-binomial model to identify ASE SNPs in only one group (i.e., DASE SNPs). We found 1479 DASE SNPs (FDR ≤ 0.05) associated with 55 beef-quality traits. Most DASE genes were involved with tenderness and muscle homeostasis, presenting a co-expression module enriched for the protein ubiquitination process. The results overlapped with epigenetics and phenotype-associated data, suggesting that DASE SNPs are potentially linked to cis-regulatory variants affecting simultaneously the transcription and phenotype through chromatin state modulation.


Subject(s)
Meat , Muscle, Skeletal , Cattle/genetics , Animals , Alleles , Phenotype , Genotype , Muscle, Skeletal/metabolism
14.
PLoS One ; 17(12): e0279091, 2022.
Article in English | MEDLINE | ID: mdl-36548260

ABSTRACT

Evolutionary history leads to genome changes over time, especially for species that have experienced intense selective pressures over a short period. Here, we investigated the genomic evolution of Bos species by searching for potential selection signatures, focusing on Nelore, an economically relevant cattle breed in Brazil. We assessed the genomic processes determining the molecular evolution across Nelore and thirteen other related taxa by evaluating (i) amino acid sequence conservation, (ii) the dN/dS ratio, and (iii) gene families' turnover rate (λ). Low conserved regions potentially associated with fatty acid metabolism seem to reflect differences in meat fat content in taxa with different evolutionary histories. All Bos species presented genes under positive selection, especially B. indicus and Nelore, which include transport protein cobalamin, glycolipid metabolism, and hormone signaling. These findings could be explained by constant selective pressures to obtain higher immune resistance and efficient metabolism. The gene contraction rate across the Nelore + B. indicus branch was almost nine times higher than that in other lineages (λ = 0.01043 vs. 0.00121), indicating gene losses during the domestication process. Amino acid biosynthesis, reproductive and innate immune system-related pathways were associated with genes recognized within the most frequent rapidly evolving gene families and in genes under positive selection, supporting the substantial relevance of such traits from a domestication perspective. Our data provide new insights into how the genome may respond to intense artificial selection in distinct taxa, and reinforces the presence of selective pressures on traits potentially relevant for future animal breeding investments.


Subject(s)
Genome , Genomics , Animals , Cattle , Phenotype , Evolution, Molecular , Brazil
15.
Front Genet ; 13: 948240, 2022.
Article in English | MEDLINE | ID: mdl-36338989

ABSTRACT

Data integration using hierarchical analysis based on the central dogma or common pathway enrichment analysis may not reveal non-obvious relationships among omic data. Here, we applied factor analysis (FA) and Bayesian network (BN) modeling to integrate different omic data and complex traits by latent variables (production, carcass, and meat quality traits). A total of 14 latent variables were identified: five for phenotype, three for miRNA, four for protein, and two for mRNA data. Pearson correlation coefficients showed negative correlations between latent variables miRNA 1 (mirna1) and miRNA 2 (mirna2) (-0.47), ribeye area (REA) and protein 4 (prot4) (-0.33), REA and protein 2 (prot2) (-0.3), carcass and prot4 (-0.31), carcass and prot2 (-0.28), and backfat thickness (BFT) and miRNA 3 (mirna3) (-0.25). Positive correlations were observed among the four protein factors (0.45-0.83): between meat quality and fat content (0.71), fat content and carcass (0.74), fat content and REA (0.76), and REA and carcass (0.99). BN presented arcs from the carcass, meat quality, prot2, and prot4 latent variables to REA; from meat quality, REA, mirna2, and gene expression mRNA1 to fat content; from protein 1 (prot1) and mirna2 to protein 5 (prot5); and from prot5 and carcass to prot2. The relations of protein latent variables suggest new hypotheses about the impact of these proteins on REA. The network also showed relationships among miRNAs and nebulin proteins. REA seems to be the central node in the network, influencing carcass, prot2, prot4, mRNA1, and meat quality, suggesting that REA is a good indicator of meat quality. The connection among miRNA latent variables, BFT, and fat content relates to the influence of miRNAs on lipid metabolism. The relationship between mirna1 and prot5 composed of isoforms of nebulin needs further investigation. The FA identified latent variables, decreasing the dimensionality and complexity of the data. The BN was capable of generating interrelationships among latent variables from different types of data, allowing the integration of omics and complex traits and identifying conditional independencies. Our framework based on FA and BN is capable of generating new hypotheses for molecular research, by integrating different types of data and exploring non-obvious relationships.

16.
Biochim Biophys Acta Gene Regul Mech ; 1865(8): 194886, 2022 11.
Article in English | MEDLINE | ID: mdl-36265837

ABSTRACT

Single nucleotide polymorphisms showing allele-specific expression (ASE SNPs) are useful for cis-regulatory variants discovery. Despite this potential, there are expensive costs involved in genome-level ASE analysis for large sample sizes. If different data resolutions are available, genotype imputation can be used to mitigate this limitation. Aiming to increase the power to detect regulatory variants, we used a large dataset (>4 million) of imputed SNP genotypes and RNA-Seq data from 190 Nelore steers. Differences between major and minor allele expressions in muscle were tested with a Binomial Test. We identified 38,177 ASE SNPs (FDR ≤ 0.05) within 7304 linkage disequilibrium blocks. After that, we searched for aseQTLs (i.e., neighboring SNPs potentially regulating the ASE SNPs' allelic expression) by comparing the ASE of heterozygous to homozygous sample groups under a Wilcoxon Rank Sum test. We identified 21,543 aseQTLs potentially regulating 430 ASE SNPs (FDR ≤ 0.05). A total of 3333 cis-eQTLs (being 2098 ASE SNPs and 1075 aseQTLs) were associated with the expression of 758 transcripts (FDR ≤ 0.05), demonstrating the cis-regulatory effect of these ASE SNPs and aseQTLs. Data integration showed reproducibility with previous studies in bovine ASE and genomic imprinting. Furthermore, we identified 36,756 novel ASE regions due to the imputation approach. Comparisons with epigenetics data from Functional Annotation of Animal Genomes (FAANG) suggest a regulatory potential of the ASE-related SNPs. The affected genes were enriched in metabolic pathways essential for muscle homeostasis. These findings reinforce the potential of using ASE for discovering cis-regulatory SNPs that may affect muscle-related traits.


Subject(s)
Polymorphism, Single Nucleotide , Quantitative Trait Loci , Cattle/genetics , Animals , Alleles , Reproducibility of Results , Muscles
18.
Front Genet ; 13: 935238, 2022.
Article in English | MEDLINE | ID: mdl-35991540

ABSTRACT

Understanding the architecture of gene expression is fundamental to unravel the molecular mechanisms regulating complex traits in bovine, such as intramuscular fat content (IMF) and backfat thickness (BFT). These traits are economically important for the beef industry since they affect carcass and meat quality. Our main goal was to identify gene expression regulatory polymorphisms within genomic regions (QTL) associated with IMF and BFT in Nellore cattle. For that, we used RNA-Seq data from 193 Nellore steers to perform SNP calling analysis. Then, we combined the RNA-Seq SNP and a high-density SNP panel to obtain a new dataset for further genome-wide association analysis (GWAS), totaling 534,928 SNPs. GWAS was performed using the Bayes B model. Twenty-one relevant QTL were associated with our target traits. The expression quantitative trait loci (eQTL) analysis was performed using Matrix eQTL with the complete SNP dataset and 12,991 genes, revealing a total of 71,033 cis and 36,497 trans-eQTL (FDR < 0.05). Intersecting with QTL for IMF, we found 231 eQTL regulating the expression levels of 117 genes. Within those eQTL, three predicted deleterious SNPs were identified. We also identified 109 eQTL associated with BFT and affecting the expression of 54 genes. This study revealed genomic regions and regulatory SNPs associated with fat deposition in Nellore cattle. We highlight the transcription factors FOXP4, FOXO3, ZSCAN2, and EBF4, involved in lipid metabolism-related pathways. These results helped us to improve our knowledge about the genetic architecture behind important traits in cattle.

19.
Animals (Basel) ; 12(13)2022 Jun 25.
Article in English | MEDLINE | ID: mdl-35804531

ABSTRACT

The aim of this study was to identify the differentially expressed genes (DEG) from the skeletal muscle and liver samples of animal models for metabolic diseases in humans. To perform the study, the fatty acid (FA) profile and RNA sequencing (RNA-Seq) data of 35 samples of liver tissue (SOY1.5, n = 17 and SOY3.0, n = 18) and 36 samples of skeletal muscle (SOY1.5, n = 18 and SOY3.0, n = 18) of Large White pigs were analyzed. The FA profile of the tissues was modified by the diet, mainly those related to monounsaturated (MUFA) and polyunsaturated (PUFA) FA. The skeletal muscle transcriptome analysis revealed 45 DEG (FDR 10%), and the functional enrichment analysis identified network maps related to inflammation, immune processes, and pathways associated with oxidative stress, type 2 diabetes, and metabolic dysfunction. For the liver tissue, the transcriptome profile analysis revealed 281 DEG, which participate in network maps related to neurodegenerative diseases. With this nutrigenomics study, we verified that different levels of soybean oil in the pig diet, an animal model for metabolic diseases in humans, affected the transcriptome profile of skeletal muscle and liver tissue. These findings may help to better understand the biological mechanisms that can be modulated by the diet.

20.
Mamm Genome ; 33(4): 629-641, 2022 12.
Article in English | MEDLINE | ID: mdl-35840822

ABSTRACT

Animal feeding is a critical factor in increasing producer profitability. Improving feed efficiency can help reduce feeding costs and reduce the environmental impact of beef production. Candidate genes previously identified for this trait in differential gene expression studies (e.g., case-control studies) have not examined continuous gene-phenotype variation, which is a limitation. The aim of this study was to investigate the association between the expression of five candidate genes in the liver, measured by quantitative real-time PCR and feed-related traits. We adopted a linear mixed model to associate liver gene expression from 52 Nelore steers with the following production traits: average daily gain (ADG), body weight (BW), dry matter intake (DMI), feed conversion ratio (FCR), feed efficiency (FE), Kleiber index (KI), metabolic body weight (MBW), residual feed intake (RFI), and relative growth ratio (RGR). The total expression of the prune homolog 2 (PRUNE2) gene was significantly associated with DMI, FCR, FE, and RFI (P < 0.05). Furthermore, we have identified a new transcript of PRUNE2 (TCONS_00027692, GenBank MZ041267) that was inversely correlated with FCR and FE (P < 0.05), in contrast to the originally identified PRUNE2 transcript. The cytochrome P450 subfamily 2B (CYP2B6), early growth response protein 1 (EGR1), collagen type I alpha 1 chain (COL1A1), and connective tissue growth factor (CTGF) genes were not associated with any feed efficiency-related traits (P > 0.05). The findings reported herein suggest that PRUNE2 expression levels affects feed efficiency-related traits variation in Nelore steers.


Subject(s)
Animal Feed , Eating , Cattle/genetics , Animals , Eating/genetics , Phenotype , Animal Feed/analysis , Body Weight/genetics , Gene Expression
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