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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. Made available in DSpace on 2022-08-31T17:19:21Z (GMT). No. of bitstreams: 1 IntegrativeAnalysisGenome.pdf: 2535243 bytes, checksum: 35d58fc8ea8d23d9de8f88c60d2e1959 (MD5) Previous issue date: 2022

Dietary fatty acids (FA) are components of the lipids, which contribute to membrane structure, energy input, and biological functions related to cellular signaling and transcriptome regulation. However, the consumers still associate dietary FA with fat deposition and increased occurrence of metabolic diseases such as obesity and atherosclerosis. Previous studies already demonstrated that some fatty acids are linked with inflammatory response, preventing metabolic diseases. To better understand the role of dietary FA on metabolic diseases, for the first time, a study to identify key transcription factors (TF) involved in lipid metabolism and inflammatory response by transcriptome analysis from liver samples of animal models was performed. The key TF were identified by functional enrichment analysis from the list of differentially expressed genes identified in liver samples between 35 pigs fed with 1.5% or 3.0% soybean oil. The functional enrichment analysis detected TF linked to lipid homeostasis and inflammatory response, such as RXRA, EGFR, and SREBP2 precursor. These findings demonstrated that key TF related to lipid metabolism could be modulated by dietary inclusion of soybean oil. It could contribute to nutrigenomics research field that aims to elucidate dietary interventions in animal and human health, as well as to drive food technology and science. Made available in DSpace on 2022-09-01T12:19:51Z (GMT). No. of bitstreams: 1 EffectDietarySoybean.pdf: 2026003 bytes, checksum: 71bbe130056faedb79fc4fbe820d4371 (MD5) Previous issue date: 2022

Background Beef tenderness is a complex trait of economic importance for the beef industry. Understanding the epigenetic mechanisms underlying this trait may help improve the accuracy of breeding programs. However, little is known about epigenetic effects on Bos taurus muscle and their implications in tenderness, and no studies have been conducted in Bos indicus. Results Comparing methylation profile of Bos indicus skeletal muscle with contrasting beef tenderness at 14 days after slaughter, we identified differentially methylated cytosines and regions associated with this trait. Interestingly, muscle that became tender beef had higher levels of hypermethylation compared to the tough group. Enrichment analysis of predicted target genes suggested that differences in methylation between tender and tough beef may affect signal transduction pathways, among which G protein signaling was a key pathway. In addition, different methylation levels were found associated with expression levels of GNAS, PDE4B, EPCAM and EBF3 genes. The differentially methylated elements correlated with EBF3 and GNAS genes overlapped CpG islands and regulatory elements. GNAS, a complex imprinted gene, has a key role on G protein signaling pathways. Moreover, both G protein signaling pathway and the EBF3 gene regulate muscle homeostasis, relaxation, and muscle cell-specificity. Conclusions We present differentially methylated loci that may be of interest to decipher the epigenetic mechanisms affecting tenderness. Supported by the previous knowledge about regulatory elements and gene function, the methylation data suggests EBF3 and GNAS as potential candidate genes and G protein signaling as potential candidate pathway associated with beef tenderness via methylation.

Background: The impact of extreme changes in weather patterns on the economy and human welfare is one of the biggest challenges our civilization faces. From anthropogenic contributions to climate change, reducing the impact of farming activities is a priority since it is responsible for up to 18% of global greenhouse gas emissions. To this end, we tested whether ruminal and stool microbiome components could be used as biomarkers for methane emission and feed efficiency in bovine by studying 52 Brazilian Nelore bulls belonging to two feed intervention treatment groups, that is, conventional and by-product-based diets.Results: We identified a total of 5,693 amplicon sequence variants (ASVs) in the Nelore bulls’ microbiomes. A Differential abundance analysis with the ANCOM approach identified 30 bacterial and 15 archaeal ASVs as differentially abundant (DA) among treatment groups. An association analysis using Maaslin2 software and a linear mixed model indicated that bacterial ASVs are linked to the host’s residual methane emission (RCH4) and residual feed intake (RFI) phenotype variation, suggesting their potential as targets for interventions or biomarkers.Conclusion: The feed composition induced significant differences in both abundance and richness of ruminal and stool microbial populations in ruminants of the Nelore breed. The industrial by-product-based dietary treatment applied to our experimental groups influenced the microbiome diversity of bacteria and archaea but not of protozoa. ASVs were associated with RCH4 emission and RFI in ruminal and stool microbiomes. While ruminal ASVs were expected to influence CH4 emission and RFI, the relationship of stool taxa, such as Alistipes and Rikenellaceae (gut group RC9), with these traits was not reported before and might be associated with host health due to their link to anti-inflammatory compounds. Overall, the ASVs associated here have the potential to be used as biomarkers for these complex phenotypes.

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. Made available in DSpace on 2022-09-01T17:22:23Z (GMT). No. of bitstreams: 1 DifferentialGeneExpression.pdf: 874144 bytes, checksum: ee5fff9b1b4001d34b97ada9c0192841 (MD5) Previous issue date: 2022

Made available in DSpace on 2022-04-29T08:41:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-04-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Analyses of livestock genomes have been used to detect selection signatures, which are genomic regions associated with traits under selection leading to a change in allele frequency. The objective of the present study was to characterize selection signatures in Canchim composite beef cattle using cross-population analyses with the founder Nelore and Charolais breeds. High-density single nucleotide polymorphism genotypes were available on 395 Canchim representing the target population, along with genotypes from 809 Nelore and 897 Charolais animals representing the reference populations. Most of the selection signatures were co-located with genes whose functions agree with the expectations of the breeding programs; these genes have previously been reported to associate with meat quality, as well as reproductive traits. Identified genes were related to immunity, adaptation, morphology, as well as behavior, could give new perspectives for understanding the genetic architecture of Canchim. Some selection signatures identified genes that were recently introduced in Canchim, such as the loci related to the polled trait. Departamento de Zootecnia Universidade Federal da Paraíba, Areia, Paraíba Embrapa Southeast Livestock, São Carlos Departamento de Engenharia e Ciências Exatas Universidade Estadual Paulista, Jaboticabal Teagasc Animal & Grassland Research and Innovation Centre, Moorepark Fermoy Co. Cork Departamento de Engenharia e Ciências Exatas Universidade Estadual Paulista, Jaboticabal CNPq: 430379/2018-8

Cattle population history, breeding systems, and geographic subdivision may be reflected in runs of homozygosity (ROH), effective population size (Ne), and linkage disequilibrium (LD) patterns. Thus, the assessment of this information has become essential to the implementation of genomic selection on purebred and crossbred cattle breeding programs. In this way, we assessed the genotype of 19 cattle breeds raised in Brazil belonging to taurine, indicine, synthetic crossbreds, and Iberian-derived locally adapted ancestries to evaluate the overall LD decay patterns, Ne, ROH, and breed composition. We were able to obtain a general overview of the genomic architecture of cattle breeds currently raised in Brazil and other tropical countries. We found that, among the evaluated breeds, different marker densities should be used to improve the genomic prediction accuracy and power of genome-wide association studies. Breeds showing low Ne values indicate a recent inbreeding, also reflected by the occurrence of longer ROH, which demand special attention in the matting schemes to avoid extensive inbreeding. Candidate genes (e.g., ABCA7, PENK, SPP1, IFNAR1, IFNAR2, SPEF2, PRLR, LRRTM1, and LRRTM4) located in the identified ROH islands were evaluated, highlighting biological processes involved with milk production, behavior, rusticity, and fertility. Furthermore, we were successful in obtaining the breed composition regarding the taurine and indicine composition using single-nucleotide polymorphism (SNP) data. Our results were able to observe in detail the genomic backgrounds that are present in each breed and allowed to better understand the various contributions of ancestor breeds to the modern breed composition to the Brazilian cattle.

We conducted a study to identify the fecal metabolite profle and its proximity to the ruminal metabolism of Nelore steers based on an untargeted metabolomic approach. Twenty-six Nelore were feedlot with same diet during 105 d. Feces and rumen fuid were collected before and at slaughter, respectively. The metabolomics analysis indicated 49 common polar metabolites in the rumen and feces. Acetate, propionate, and butyrate were the most abundant polar metabolites in both bio-samples. The rumen presented signifcantly higher concentrations of the polar compounds when compared to feces (P< 0.05); even though, fecal metabolites presented an accentuated representability of the ruminal fuid metabolites. All fatty acids present in the ruminal fuid were also observed in the feces, except for C20:2n6 and C20:4n6. The identifed metabolites ofer information on the main metabolic pathways (higher impact factor and P< 0.05), as synthesis and degradation of ketone bodies; the alanine, aspartate and glutamate metabolisms, the glycine, serine; and threonine metabolism and the pyruvate metabolism. The fndings reported herein on the close relationship between the ruminal fuid and feces metabolic profles may ofer new metabolic information, in addition to facilitating the sampling for metabolism investigation in animal production and health routines. Made available in DSpace on 2021-12-13T15:00:43Z (GMT). No. of bitstreams: 1 ComparativeUntargetedMetabolome.pdf: 1971534 bytes, checksum: 04cf77d8b820aee368be3ff254d22a28 (MD5) Previous issue date: 2021

Single nucleotide polymorphisms (SNPs) located in transcript sequences showing allele-specific expression (ASE SNPs) were previously identified in the Longissimus thoracis muscle of a Nelore (Bos indicus) population consisting of 190 steers. Given that the allele-specific expression pattern may result from cis-regulatory SNPs, called allele-specific expression quantitative trait loci (aseQTLs), in this study, we searched for aseQTLs in a window of 1 Mb upstream and downstream from each ASE SNP. After this initial analysis, aiming to investigate variants with a potential regulatory role, we further screened our aseQTL data for sequence similarity with transcription factor binding sites and microRNA (miRNA) binding sites. These aseQTLs were overlapped with methylation data from reduced representation bisulfite sequencing (RRBS) obtained from 12 animals of the same population. We identified 1134 aseQTLs associated with 126 different ASE SNPs. For 215 aseQTLs, one allele potentially affected the affinity of a muscle-expressed transcription factor to its binding site. 162 aseQTLs were predicted to affect 149 miRNA binding sites, from which 114 miRNAs were expressed in muscle. Also, 16 aseQTLs were methylated in our population. Integration of aseQTL with GWAS data revealed enrichment for traits such as meat tenderness, ribeye area, and intramuscular fat . To our knowledge, this is the first report of aseQTLs identification in bovine muscle. Our findings indicate that various cis-regulatory and epigenetic mechanisms can affect multiple variants to modulate the allelic expression. Some of the potential regulatory variants described here were associated with the expression pattern of genes related to interesting phenotypes for livestock. Thus, these variants might be useful for the comprehension of the genetic control of these phenotypes. Made available in DSpace on 2021-08-17T12:02:54Z (GMT). No. of bitstreams: 1 MuscleAlleleSpecific.pdf: 13183203 bytes, checksum: a634e71a998500cd0f7dd0ad1e644846 (MD5) Previous issue date: 2021 Article number: 7321.

Background: SARS-CoV-2 is an RNA virus causing COVID-19. The clinical characteristics and epidemiology of COVID-19 have been extensively investigated, however, only one study so far focused on the patient?s nasopharynx microbiota. In this study we investigated the nasopharynx microbial community of patients that developed different severity levels of COVID-19. We performed 16S ribosomal DNA sequencing from nasopharyngeal swab samples obtained from SARS-CoV-2 positive (56) and negative (18) patients in the province of Alicante (Spain) in their first visit to the hospital. Positive SARS-CoV-2 patients were observed and later categorized in mild (symptomatic without hospitalization), moderate (hospitalization), and severe (admission to ICU). We compared the microbiota diversity and OTU composition among severity groups and built bacterial co-abundance networks for each group. Results: Statistical analysis indicated differences in the nasopharyngeal microbiome of COVID19 patients. 62 OTUs were found exclusively in SARS-CoV-2 positive patients, mostly classified as members of the phylum Bacteroidota (18) and Firmicutes (25). OTUs classified as Prevotella were found to be significantly more abundant in patients that developed more severe COVID-19. Furthermore, co-abundance analysis indicated a loss of network complexity among samples from patients that later developed more severe symptoms. Conclusion: Our study shows that the nasopharyngeal microbiome of COVID-19 patients showed differences in the composition of specific OTUs and complexity of co-abundance networks. Taxa with differential abundances among groups could serve as biomarkers for COVID-19 severity. Nevertheless, further studies with larger sample sizes should be conducted to validate these results. Made available in DSpace on 2021-07-04T02:17:32Z (GMT). No. of bitstreams: 1 NasopharyngealMicrobialCommunities.pdf: 5123252 bytes, checksum: 132be8c592f0639000487b505f01db6d (MD5) Previous issue date: 2021

Differences between the expression of the two alleles of a gene are known as allele-specific expression (ASE), a common event in the transcriptome of mammals. Despite ASE being a source of phenotypic variation, its occurrence and effects on genetic prediction of economically relevant traits are still unexplored in bovines. Furthermore, as ASE events are likely driven by cis-regulatory mutations, scanning them throughout the bovine genome represents a significant step to elucidate the mechanisms underlying gene expression regulation. To address this question in a Bos indicus population, we built the ASE profile of the skeletal muscle tissue of 190 Nelore steers, using RNA sequencing data and SNPs genotypes from the Illumina BovineHD BeadChip (770 K bp). After quality control, 820 SNPs showed at least one sample with ASE. These SNPs were widespread among all autosomal chromosomes, being 32.01% found in 3'UTR and 31.41% in coding regions. We observed a considerable variation of ASE profile among individuals, which highlighted the need for biological replicates in ASE studies. Functional analysis revealed that ASE genes play critical biological functions in the development and maintenance of muscle tissue. Additionally, some of these genes were previously reported as associated with beef production and quality traits in livestock, thus indicating a possible source of bias on genomic predictions for these traits. Made available in DSpace on 2020-10-10T09:14:31Z (GMT). No. of bitstreams: 1 AP-Allele-specific-2020.pdf: 1969866 bytes, checksum: 3b858fd65a6e059a02cd3b893d37b41c (MD5) Previous issue date: 2020 Na publicação: Adhemar Zerlotini. Article number: 10204.

Background The success of different species of ruminants in the colonization of a diverse range of environments is due to their ability to digest and absorb nutrients from cellulose, a complex polysaccharide found in leaves and grass. Ruminants rely on a complex and diverse microbial community, or microbiota, in a unique compartment known as the rumen to break down this polysaccharide. Changes in microbial populations of the rumen can affect the host’s development, health, and productivity. However, accessing the rumen is stressful for the animal. Therefore, the development and use of alternative sampling methods are needed if this technique is to be routinely used in cattle breeding. To this end, we tested if the fecal microbiome could be used as a proxy for the rumen microbiome due to its accessibility. We investigated the taxonomic composition, diversity and inter-relations of two different GIT compartments, rumen and feces, of 26 Nelore (Bos indicus) bulls, using Next Generation Sequencing (NGS) metabarcoding of bacteria, archaea and ciliate protozoa. Results We identified 4265 Amplicon Sequence Variants (ASVs) from bacteria, 571 from archaea, and 107 from protozoa, of which 143 (96 bacteria and 47 archaea) were found common between both microbiomes. The most prominent bacterial phyla identified were Bacteroidetes (41.48%) and Firmicutes (56.86%) in the ruminal and fecal microbiomes, respectively, with Prevotella and Ruminococcaceae UCG-005 the most relatively abundant genera identified in each microbiome. The most abundant archaeal phylum identified was Euryarchaeota, of which Methanobrevibacter gottschalkii, a methanogen, was the prevalent archaeal species identified in both microbiomes. Protozoa were found exclusively identified in the rumen with Bozasella/Triplumaria being the most frequent genus identified. Co-occurrence among ruminal and fecal ASVs reinforces the relationship of microorganisms within a biological niche. Furthermore, the co-occurrence of shared archaeal ASVs between microbiomes indicates a dependency of the predominant fecal methanogen population on the rumen population. Conclusions Co-occurring microorganisms were identified within the rumen and fecal microbiomes, which revealed a strong association and inter-dependency between bacterial, archaeal and protozoan populations of the same microbiome. The archaeal ASVs identified as co-occurring between GIT compartments corresponded to the methanogenic genera Methanobrevibacter and Methanosphaera and represented 26.34% of the overall archaeal sequencesdiversity in the rumen and 42.73% in feces. Considering that these archaeal ASVs corresponded to a significant part of the overall diversity of both microbiomes, which is much higher if one includes the interactions of these co-occurring with other rumen archaea ASVs, we suggest that fecal methanogens could be used as a proxy of ruminal methanogens.

Made available in DSpace on 2022-04-29T08:28:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-03-01 Improving the efficiency of production to reduce the environmental footprints is pivotal to the sustainability of livestock systems. Despite the advances in cattle feed efficiency (FE) measurement and identification of potential mechanisms involved, much is still unclear regarding the genetic and biological basis of this trait. Nevertheless, lipid and carbohydrate metabolism have been outlined as important in determining efficient and inefficient animals. To address the role of genes partaking in these processes and previously involved with residual feed intake (RFI), we carried out a liver expression profile in Nelore steers (n = 83). Six target genes (FABP1, FADS2, PPP1R26, RGS2, SLC2A5, and UCP2) were measured by qPCR analysis. A general linear mixed model approach was applied to associate them with dry matter intake (DMI), body weight (BW), metabolic BW (MBW, kg), DMI as a percentage of BW (DMI%BW), and average daily gain (ADG, kg/d). Residual feed intake (RFI), feed conversion ratio (FCR), feed efficiency (FE), Kleiber index (KI), and relative growth rate (RGR) were also evaluated. Our results support that increased expression of FABP1 gene was associated with enhanced values for RFI and DMI. Likewise, higher expression level of SLC2A5 was related to higher KI and RGR. There was no phenotypic correlation between RFI and ADG, BW, and MBW. The positive correlations between FABP1 and SLC2A5, and between FABP1 and FADS2 gene expression suggest a putative co-regulation affecting feed efficiency phenotypes. Center for Biological and Health Sciences (CCBS) Federal University of São Carlos, São Carlos Department of Animal Science São Paulo State University Julio de Mesquita Filho, Jaboticabal NGS Soluções Genômicas, Piracicaba Department of Animal Science University of São Paulo/ESALQ, Piracicaba Embrapa Pecuária Sudeste, São Carlos Department of Animal Science Iowa State University Department of Animal Science São Paulo State University Julio de Mesquita Filho, Jaboticabal

Feed efficiency helps to reduce environmental impacts from livestock production, improving beef cattle profitability. We identified potential biomarkers (hub genes) for feed efficiency, by applying co-expression analysis in Longissimus thoracis RNA-Seq data from 180 Nelore steers. Six co-expression modules were associated with six feed efficiency-related traits (p-value ≤ 0.05). Within these modules, 391 hub genes were enriched for pathways as protein synthesis, muscle growth, and immune response. Trait-associated transcription factors (TFs) ELF1, ELK3, ETS1, FLI1, and TCF4, were identified with binding sites in at least one hub gene. Gene expression of CCDC80, FBLN5, SERPINF1, and OGN was associated with multiple feed efficiency-related traits (FDR ≤ 0.05) and were previously related to glucose homeostasis, oxidative stress, fat mass, and osteoblastogenesis, respectively. Potential regulatory elements were identified, integrating the hub genes with previous studies from our research group, such as the putative cis-regulatory elements (eQTLs) inferred as affecting the PCDH18 and SPARCL1 hub genes related to immune system and adipogenesis, respectively. Therefore, our analyses contribute to a better understanding of the biological mechanisms underlying feed efficiency in bovine and the hub genes disclosed can be used as biomarkers for feed efficiency-related traits in Nelore cattle. Made available in DSpace on 2020-08-15T04:11:44Z (GMT). No. of bitstreams: 1 AP-Potential-biomarkers-2020.pdf: 6772400 bytes, checksum: b6d50a8237cd649b3e08ecc7fb04b44e (MD5) Previous issue date: 2020 Article 189. Na publicação: Luciana C. A. Regitano.

Residual Feed Intake (RFI) is an economically relevant trait in beef cattle. Among the molecular regulatory mechanisms, microRNAs (miRNAs) are an important dimension in post-transcriptional regulation and have been associated with different biological pathways. Here, we performed differential miRNAs expression and weighted gene co-expression network analyses (WGCNA) to better understand the complex interactions between miRNAs and mRNAs expressed in bovine skeletal muscle and liver. MiRNA and mRNA expression data were obtained from Nelore steers that were genetically divergent for RFI (N = 10 [low RFI or feed efficient]; N = 10 [high RFI or feed inefficient]). Differentially expressed and hub miRNAs such as bta-miR-486, bta-miR-7, bta-miR15a, bta-miR-21, bta-miR 29, btamiR-30b, bta-miR-106b, bta-miR-199a-3p, bta-miR-204, and bta-miR 296 may have a potential role in variation of RFI. Functional enrichment analysis of differentially expressed (DE) miRNA?s target genes and miRNA?mRNA correlated modules revealed that insulin, lipid, immune system, oxidative stress and muscle development signaling pathways might potentially be involved in RFI in this population. Our study identified DE miRNAs, miRNA - mRNA regulatory networks and hub miRNAs related to RFI. These findings suggest a possible role of miRNAs in regulation of RFI, providing new insights into the potential molecular mechanisms that control feed efficiency in Nelore cattle. Made available in DSpace on 2018-12-22T23:31:58Z (GMT). No. of bitstreams: 1 APIntegrativeAdhemaretal.pdf: 1483055 bytes, checksum: 14efe405fca6e8d91642f5067590314b (MD5) Previous issue date: 2018-12-20 Article number: 17072. Na publicação: Adhemar Zerlotini, Luciana C. A. Regitano.

Background Commercial cuts yield is an important trait for beef production, which affects the final value of the products, but its direct determination is a challenging procedure to be implemented in practice. The measurement of ribeye area (REA) and backfat thickness (BFT) can be used as indirect measures of meat yield. REA and BFT are important traits studied in beef cattle due to their strong implication in technological (carcass yield) and nutritional characteristics of meat products, like the degree of muscularity and total body fat. Thus, the aim of this work was to study the Longissimus dorsi muscle transcriptome of Nellore cattle, associated with REA and BFT, to find differentially expressed (DE) genes, metabolic pathways, and biological processes that may regulate these traits. Results By comparing the gene expression level between groups with extreme genomic estimated breeding values (GEBV), 101 DE genes for REA and 18 for BFT (false discovery rate, FDR 10%) were identified. Functional enrichment analysis for REA identified two KEGG pathways, MAPK (Mitogen-Activated Protein Kinase) signaling pathway and endocytosis pathway, and three biological processes, response to endoplasmic reticulum stress, cellular protein modification process, and macromolecule modification. The MAPK pathway is responsible for fundamental cellular processes, such as growth, differentiation, and hypertrophy. For BFT, 18 biological processes were found to be altered and grouped into 8 clusters of semantically similar terms. The DE genes identified in the biological processes for BFT were ACHE, SRD5A1, RSAD2 and RSPO3. RSAD2 has been previously shown to be associated with lipid droplet content and lipid biosynthesis. Conclusion In this study, we identified genes, metabolic pathways, and biological processes, involved in differentiation, proliferation, protein turnover, hypertrophy, as well as adipogenesis and lipid biosynthesis related to REA and BFT. These results enlighten some of the molecular processes involved in muscle and fat deposition, which are economically important carcass traits for beef production. Electronic supplementary material The online version of this article (doi:10.1186/s12864-017-3897-x) contains supplementary material, which is available to authorized users.

Mineral contents in bovine muscle can affect meat quality, growth, health, and reproductive traits. To better understand the genetic basis of this phenotype in Nelore (Bos indicus) cattle, we analysed genome-wide mRNA and miRNA expression data from 114 muscle samples. The analysis implemented a new application for two complementary algorithms: the partial correlation and information theory (PCIT) and the regulatory impact factor (RIF), in which we included the estimated genomic breeding values (GEBVs) for the phenotypes additionally to the expression levels, originally proposed for these methods. We used PCIT to determine putative regulatory relationships based on significant associations between gene expression and GEBVs for each mineral amount. Then, RIF was adopted to determine the regulatory impact of genes and miRNAs expression over the GEBVs for the mineral amounts. We also investigated over-represented pathways, as well as pieces of evidences from previous studies carried in the same population and in the literature, to determine regulatory genes for the mineral amounts. For example, NOX1 expression level was positively correlated to Zinc and has been described as Zinc-regulated in humans. Based on our approach, we were able to identify genes, miRNAs and pathways not yet described as underlying mineral amount. The results support the hypothesis that extracellular matrix interactions are the core regulator of mineral amount in muscle cells. Putative regulators described here add information to this hypothesis, expanding the knowledge on molecular relationships between gene expression and minerals. Made available in DSpace on 2020-09-09T04:37:14Z (GMT). No. of bitstreams: 1 AP-Genetic-regulators-2020.pdf: 3953162 bytes, checksum: f7f057405a94ac732a64d0f4b4788219 (MD5) Previous issue date: 2020 Article: 8436.

Fatty acid (FA) content affects the sensorial and nutritional value of meat and plays a significant role in biological processes such as adipogenesis and immune response. It is well known that, in beef, the main FAs associated with these biological processes are oleic acid (C18:1 cis9, OA) and conjugated linoleic acid (CLA-c9t11), which may have beneficial effects on metabolic diseases such as type 2 diabetes and obesity. Here, we performed differential expression and co-expression analyses, weighted gene co-expression network analysis (WGCNA) and partial correlation with information theory (PCIT), to uncover the complex interactions between miRNAs and mRNAs expressed in skeletal muscle associated with FA content. miRNA and mRNA expression data were obtained from skeletal muscle of Nelore cattle that had extreme genomic breeding values for OA and CLA. Insulin and MAPK signaling pathways were identified by WGCNA as central pathways associated with both of these fatty acids. Co-expression network analysis identified bta-miR-33a/b, bta-miR-100, bta-miR-204, bta-miR-365-5p, btamiR-660, bta-miR-411a, bta-miR-136, bta-miR-30-5p, bta-miR-146b, bta-let-7a-5p, bta-let-7f, bta-let-7, bta-miR 339, bta-miR-10b, bta-miR 486, and the genes ACTA1 and ALDOA as potential regulators of fatty acid synthesis. This study provides evidence and insights into the molecular mechanisms and potential target genes involved in fatty acid content differences in Nelore beef cattle, revealing new candidate pathways of phenotype modulation that could positively benefit beef production and human consumption. Made available in DSpace on 2019-07-25T01:02:05Z (GMT). No. of bitstreams: 1 APCoexpressionnetworks.pdf: 1517209 bytes, checksum: c6c99bbfd9721e2c08e0d765e8b03b88 (MD5) Previous issue date: 2019 Article 651. Na publicação: Adhemar Zerlotini, Luciana C.A. Regitano.

Summary Copy number variation (CNV) is a major type of structural genomic variation that is increasingly studied across different species for association with diseases and production traits. Established protocols for experimental detection and computational inference of CNVs from SNP array and next-generation sequencing data are available. We present the CNVRanger R/Bioconductor package which implements a comprehensive toolbox for structured downstream analysis of CNVs. This includes functionality for summarizing individual CNV calls across a population, assessing overlap with functional genomic regions, and genome-wide association analysis with gene expression and quantitative phenotypes. Availability and implementation http://bioconductor.org/packages/CNVRanger.

Background Positively correlated with carcass weight and animal growth, the ribeye area (REA) and the backfat thickness (BFT) are economic important carcass traits, which impact directly on producer’s payment. The selection of these traits has not been satisfactory since they are expressed later in the animal’s life and multigene regulated. So, next-generation technologies have been applied in this area to improve animal’s selection and better understand the molecular mechanisms involved in the development of these traits. Correlation network analysis, performed by tools like WGCNA (Weighted Correlation Network Analysis), has been used to explore gene-gene interactions and gene-phenotype correlations. Thus, this study aimed to identify putative candidate genes and metabolic pathways that regulate REA and BFT by constructing a gene co-expression network using WGCNA and RNA sequencing data, to better understand genetic and molecular variations behind these complex traits in Nelore cattle. Results The gene co-expression network analysis, using WGCNA, were built using RNA-sequencing data normalized by transcript per million (TPM) from 43 Nelore steers. Forty-six gene clusters were constructed, between them, three were positively correlated (p-value

Meat quality is a complex trait that is influenced by genetic and environmental factors, which includes mineral concentration. However, the association between mineral concentration and meat quality, and the specific molecular pathways underlying this association, are not well explored. We therefore analyzed gene expression as measured with RNA-seq in Longissimus thoracis muscle of 194 Nelore steers for association with three meat quality traits (intramuscular fat, meat pH, and tenderness) and the concentration of 13 minerals (Ca, Cr, Co, Cu, Fe, K, Mg, Mn, Na, P, S, Se, and Zn). We identified seven sets of co-expressed genes (modules) associated with at least two traits, which indicates that common pathways influence these traits. From pathway analysis of module hub genes, we further found an over-representation for energy and protein metabolism (AMPK and mTOR signaling pathways) in addition to muscle growth, and protein turnover pathways. Among the identified hub genes FASN, ELOV5, and PDE3B are involved with lipid metabolism and were affected by previously identified eQTLs associated to fat deposition. The reported hub genes and over-represented pathways provide evidence of interplay among gene expression, mineral concentration, and meat quality traits. Future studies investigating the effect of different levels of mineral supplementation in the gene expression and meat quality traits could help us to elucidate the regulatory mechanism by which the genes/pathways are affected. Made available in DSpace on 2019-03-15T18:12:26Z (GMT). No. of bitstreams: 1 fgene1000210.pdf: 8667327 bytes, checksum: 681e0f6d74f2497f0e43c36f4565a155 (MD5) Previous issue date: 2019

Analysis of a large number of markers is crucial in both genome-wide association studies (GWAS) and genome-wide selection (GWS). However there are two methodological issues that restrict statistical analysis: high dimensionality (p>>n) and multicollinearity. Although there are methodologies that can be used to fit models for data with high dimensionality (eg,the Bayesian Lasso), a big problem that can occurs in this cases is that the predictive ability of the model should perform well for the individuals used to fit the model, but should not perform well for other individuals, restricting the applicability of the model. This problem can be circumvent by applying some selection methodology to reduce the number of markers (but keeping the markers associated with the phenotypic trait) before adjusting a model to predict GBVs. We revisit a tournament-based strategy between marker samples, where each sample has good statistical properties for estimation: n>p and low collinearity. Such tournaments are elaborated using multiple linear regression to eliminate markers. This method is adapted from previous works found in the literature. We used simulated data as well as real data derived from a study with SNPs in beef cattle. Tournament strategies not only circumvent the p>>n issue, but also minimize spurious associations. For real data, when we selected a few more than 20 markers, we obtained correlations greater than 0.70 between predicted Genomic Breeding Values (GBVs) and phenotypes in validation groups of a cross-validation scheme; and when we selected a larger number of markers (more than 100), the correlations exceeded 0.90, showing the efficiency in identifying relevant SNPs (or segregations) for both GWAS and GWS. In the simulation study, we obtained similar results. Made available in DSpace on 2021-01-29T00:53:03Z (GMT). No. of bitstreams: 1 Tournaments-between-markers-as-a-strategy-correcao.pdf: 2768124 bytes, checksum: bb59f42f06963378be169c7844f995ff (MD5) Previous issue date: 2019

Background MicroRNAs (miRNAs) are small noncoding RNAs of approximately 22 nucleotides, highly conserved among species, which modulate gene expression by cleaving messenger RNA target or inhibiting translation. MiRNAs are involved in the regulation of many processes including cell proliferation, differentiation, neurogenesis, angiogenesis, and apoptosis. Beef tenderness is an organoleptic characteristic of great influence in the acceptance of meat by consumers. Previous studies have shown that collagen level, marbling, apoptosis and proteolysis are among the many factors that affect beef tenderness. Considering that miRNAs can modulate gene expression, this study was designed to identify differentially expressed miRNAs that could be modulating biological processes involved with beef tenderness. Results Deep sequence analysis of miRNA libraries from longissimus thoracis muscle allowed the identification of 42 novel and 308 known miRNAs. Among the known miRNAs, seven were specifically expressed in skeletal muscle. Differential expression analysis between animals with high (H) and low (L) estimated breeding values for shear force (EBVSF) revealed bta-mir-182 and bta-mir-183 are up-regulated (q value

Background Genetic resistance in cattle is considered a suitable way to control tick burden and its consequent losses for livestock production. Exploring tick-resistant (R) and tick-susceptible (S) hosts, we investigated the genetic mechanisms underlying the variation of Braford resistance to tick infestation. Skin biopsies from four-times-artificially infested R (n = 20) and S (n = 19) hosts, obtained before the first and 24 h after the fourth tick infestation were submitted to RNA-Sequencing. Differential gene expression, functional enrichment, and network analysis were performed to identify genetic pathways and transcription factors (TFs) affecting host resistance. Results Intergroup comparisons of hosts before (Rpre vs. Spre) and after (Rpost vs. Spost) tick infestation found 51 differentially expressed genes (DEGs), of which almost all presented high variation (TopDEGs), and 38 were redundant genes. Gene expression was consistently different between R and S hosts, suggesting the existence of specific anti-tick mechanisms. In the intragroup comparisons, Rpost vs. Rpre and Spost vs. Spre, we found more than two thousand DEGs in response to tick infestation in both resistance groups. Redundant and non-redundant TopDEGs with potential anti-tick functions suggested a role in the development of different levels of resistance within the same breed. Leukocyte chemotaxis was over-represented in both hosts, whereas skin degradation and remodeling were only found in TopDEGs from R hosts. Also, these genes indicated the participation of cytokines, such as IL6 and IL22, and the activation of Wingless (WNT)-signaling pathway. A central gene of this pathway, WNT7A, was consistently modulated when hosts were compared. Moreover, the findings based on a genome-wide association study (GWAS) corroborate the prediction of the WNT-signaling pathway as a candidate mechanism of resistance. The regulation of immune response was the most relevant pathway predicted for S hosts. Members of Ap1 and NF-kB families were the most relevant TFs predicted for R and S, respectively. Conclusion This work provides indications of genetic mechanisms presented by Braford cattle with different levels of resistance in response to tick infestation, contributing to the search of candidate genes for tick resistance in bovine.

this study compared imputation from lower-density commercial and customized panels to high-density panels and a combined panel (Illumina and Affymetrix) in Nelore beef cattle. Additionally, linkage disequilibrium and haplotype block conformation were estimated in individual high-density panels and compared with corresponding values in the combined panel after imputation. Overall, 814 animals were genotyped using BovineHD BeadChip (IllumHD), and 93 of these animals were also genotyped using the Axion Genome-Wide BOS 1 Array Plate (AffyHD). In general, customization considering linkage disequilibrium and minor allele frequency had the highest accuracies. The IllumHD panel had higher values of linkage disequilibrium for short distances between SNPs than AffyHD and the combined panel. The combined panel had an increased number of small haplotype blocks. The use of a combined panel is recommended due to its increased density and number of haplotype blocks, which in turn increase the probability of a marker being close to a quantitative trait locus of interest. Considering common SNPs between IllumHD and AffyHD for the customization of a low-density panel increases the imputation accuracy for IllumHD, AffyHD and the combined panel. Made available in DSpace on 2019-11-30T00:36:19Z (GMT). No. of bitstreams: 1 Arriguccietal2019EvaluationOfImputationAccuracy.pdf: 2103912 bytes, checksum: 643253e90289a23a33dca7f8b774eefa (MD5) Previous issue date: 2019 On-line first.

In many beef and some dairy production systems, cross breedingis used to take advan-tage of breed complementarity and heterosis. Admixed animals are frequently identified by their coat color and body conformation phenotypes, however, without pedigree informa-tionit is not possible to identify the expected breed composition of an admixed animal and in the presence of selection, the actual composition may differ from expectation. Made available in DSpace on 2019-11-29T18:09:04Z (GMT). No. of bitstreams: 1 CRUMBLERAtoolfortheprediction.pdf: 6008582 bytes, checksum: f4276ab4ce5ee73aecce16c9c1e3415c (MD5) Previous issue date: 2019 On-line first.

In eukaryotes, DNA is organized along with histones in nucleoprotein complexes known as chromatin, which has nucleosomes as their fundamental unit. Chromatin Downloaded from https://academic.oup.com/jas/article-abstract/96/suppl_3/233/5235047 by Macquarie University user on 13 February 2019 234 J. Anim. Sci Vol. 96, Suppl. S3 exists in two forms: euchromatin, corresponding to a lightly condensed structure and an easily transcribed region, and heterochromatin, a highly condensed and transcriptionally silent region. Made available in DSpace on 2019-12-17T18:07:56Z (GMT). No. of bitstreams: 1 IdentificationCharacterizationEuchromatic.pdf: 137173 bytes, checksum: bd499862036962f64fc67a0488ce9e29 (MD5) Previous issue date: 2019

Made available in DSpace on 2019-10-04T12:15:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-09-03 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Mineral content affects the biological processes underlying beef quality. Muscle mineral concentration depends not only on intake-outtake balance and muscle type, but also on age, environment, breed, and genetic factors. To unveil the genetic factors involved in muscle mineral concentration, we applied a pairwise differential gene expression analysis in groups of Nelore steers genetically divergent for nine different mineral concentrations. Here, based on significant expression differences between contrasting groups, we presented candidate genes for the genetic regulation of mineral concentration in muscle. Functional enrichment and protein-protein interaction network analyses were carried out to search for gene regulatory processes concerning each mineral. The core genetic regulation for all minerals studied, except Zn, seems to rest on interactions between components of the extracellular matrix. Regulation of adipogenesis-related pathways was also significant in our results. Antagonistic patterns of gene expression for fatty acid metabolism-related genes may explain the Cu and Zn antagonistic effect on fatty acid accumulation. Our results shed light on the role of these minerals on cell function. Univ Fed Sao Carlos, Dept Evolutionary Genet & Mol Biol, Sao Carlos, SP, Brazil Univ Sao Paulo, Dept Anim Sci, ESALQ, Piracicaba, Brazil Embrapa Pecuaria Sudeste, Sao Carlos, SP, Brazil Univ Sao Paulo, Phys Inst Sao Carlos, Sao Carlos, SP, Brazil Sao Paulo State Univ, Anim Sci Dept, Lab Mol Genet, Jaboticabal, Brazil Bahia Fed Inst Educ Sci & Technol, Ilheus, Brazil Univ Queensland, Fac Sci, Sch Chem & Mol Biosci, Brisbane, Qld, Australia NGS Solucoes Genom, Rua Ajudante Albano 847, Piracicaba, SP, Brazil Sao Paulo State Univ, Anim Sci Dept, Lab Mol Genet, Jaboticabal, Brazil FAPESP: 2012/23638-8

Genetic variations in genes involved in lipid storage, which also may interfere with important phenotypic traits such as intramuscular fat deposition in cattle, can represent useful markers in marker assisted selection programs. An important candidate gene is perilipin 2 (PLIN2) that plays a role in the capture of long chain fatty acids and in the formation and stabilization of lipid droplets in different tissues including muscle. As reported by our group, PLIN2 expression level was associated with trans-eQTL (expression quantitative loci distant of gene associated) at chr3: 87, 253, 086 in Nellore cattle, where animals with different genotypes showed different expression level of PLIN2 among the 193 animals and the co-expression analysis detected correlation with intramuscular fat, palmitoleic, oleic and linoleic acids. Then, the objective of this study was to identify and characterize polymorphisms present in the PLIN2 gene of Nellore cattle. To date, there is not much information on mutations in the PLIN2 gene in Bos indicus animals. A total of 134 single nucleotide polymorphisms (SNPs) were identified in the genomic region of PLIN2 gene and five of those are novel with a moderate impact. These SNPs may change the protein effectiveness and, after further association studies and functional validation, could be used as genomic markers in animal breeding program. Made available in DSpace on 2020-01-28T18:11:29Z (GMT). No. of bitstreams: 1 NovelPolymorphismsPLIN2.pdf: 433440 bytes, checksum: 6cc16bdaa51a68669c745c6c5bc70198 (MD5) Previous issue date: 2019 Na publicação: Luciana CA Regitano, Adhemar Zerlotini. gmr16039963.

MicroRNAs (miRNAs) are key regulators of gene expression, potentially affecting several biological processes, whose function can be altered by sequence variation. Hence, the integration of single nucleotide polymorphisms (SNP) and miRNAs can explain individual differences in economic traits. To provide new insights into the effects of SNPs on miRNAs and their related target genes, we carried out a multi-omic analysis to identify SNPs in miRNA mature sequences (miR-SNPs) associated with fatty acid (FA) composition in the Nelore cattle. As a result, we identified 3 miR-SNPs in different miRNAs (bta-miR-2419-3p, bta-miR-193a-2, and bta-miR-1291) significantly associated with FA traits (p-value &lt, 0.02, Bonferroni corrected). Among these, the rs110817643C&gt, T, located in the seed sequence of the bta-miR-1291, was associated with different &omega, 6 FAs, polyunsaturated FA, and polyunsaturated:saturated FA ratios. Concerning the other two miR-SNPs, the rs43400521T&gt, C (located in the bta-miR-2419-3p) was associated with C12:0 and C18:1 cis-11 FA, whereas the rs516857374A&gt, G (located in the bta-miR-193a-2) was associated with C18:3 &omega, 6 and ratio of &omega, 6/&omega, 3 traits. Additionally, to identify potential biomarkers for FA composition, we described target genes affected by these miR-SNPs at the mRNA or protein level. Our multi-omics analysis outlines the effects of genetic polymorphism on miRNA, and it highlights miR-SNPs and target candidate genes that control beef fatty acid composition.

Transcription factors (TFs) are pivotal regulatory proteins that control gene expression in a contextdependent and tissue-specific manner. In contrast to human, where comprehensive curated TF collections exist, bovine TFs are only rudimentary recorded and characterized. In this article, we present a manually-curated compendium of 865 sequence-specific DNA-binding bovines TFs, which we analyzed for domain family distribution, evolutionary conservation, and tissue-specific expression. In addition, we provide a list of putative transcription cofactors derived from known interactions with the identified TFs. Since there is a general lack of knowledge concerning the regulation of gene expression in cattle, the curated list of TF should provide a basis for an improved comprehension of regulatory mechanisms that are specific to the species. Made available in DSpace on 2018-12-22T23:33:30Z (GMT). No. of bitstreams: 1 APComprehensiveAdhemaretal.pdf: 3419308 bytes, checksum: b20163b62c242be3c928de00df200e8f (MD5) Previous issue date: 2018-12-20 Article number: 13747. Na publicação: Adhemar Zerlotini, Luciana C. A. Regitano.

Background: Integration of high throughput DNA genotyping and RNA-sequencing data allows for the identification of genomic regions that control gene expression, known as expression quantitative trait loci (eQTL), on a whole genome scale. Intramuscular fat (IMF) content and carcass composition play important roles in metabolic and physiological processes in mammals because they influence insulin sensitivity and consequently prevalence of metabolic diseases such as obesity and type 2 diabetes. However, limited information is available on the genetic variants and mechanisms associated with IMF deposition in mammals. Thus, our hypothesis was that eQTL analyses could identify putative regulatory regions and transcription factors (TFs) associated with intramuscular fat (IMF) content traits. Results: We performed an integrative eQTL study in skeletal muscle to identify putative regulatory regions and factors associated with intramuscular fat content traits. Data obtained from skeletal muscle samples of 192 animals was used for association analysis between 461,466 SNPs and the transcription level of 11,808 genes. This yielded 1268 cis- and 10,334 trans-eQTLs, among which we identified nine hotspot regions that each affected the expression of > 119 genes. These putative regulatory regions overlapped with previously identified QTLs for IMF content. Three of the hotspots respectively harbored the transcription factors USF1, EGR4 and RUNX1T1, which are known to play important roles in lipid metabolism. From co-expression network analysis, we further identified modules significantly correlated with IMF content and associated with relevant processes such as fatty acid metabolism, carbohydrate metabolism and lipid metabolism. Conclusion: This study provides novel insights into the link between genotype and IMF content as evident from the expression level. It thereby identifies genomic regions of particular importance and associated regulatory factors. These new findings provide new knowledge about the biological processes associated with genetic variants and mechanisms associated with IMF deposition in mammals. Made available in DSpace on 2018-12-22T23:35:36Z (GMT). No. of bitstreams: 1 APIdentificationCesaretal.pdf: 9576475 bytes, checksum: 54bfa0c637b06996ccf50a3c023171bd (MD5) Previous issue date: 2018-12-20 Article number: 499. Na publicação: Luciana C. A. Regitano, Maurício A. Mudadu, Adhemar Zerlotini.

The purpose of this study was to access and characterize single nucleotide polymorphisms (SNP) located within the HSF1 and HSPA6 candidate genes for adaptability in Angus breed raised in subtropical climate. Samples of DNA from 20 animals representing extreme phenotypes for adaptability traits were obtained. Sequence variations in the candidate genes were described by sequencing target regions. We identified 12 SNP located in the HSF1 gene. Moreover, four of the six SNP found in the HSPA6 gene cause amino acid substitutions in protein-coding regions. We also identified a representative SNP (called tag SNP) in a region of the HSF1 gene with high linkage disequilibrium (r2 = 0.87) that may represent 11 SNP located in this gene. Minor allele frequency observed for the SNP ranged from 0.10 to 0.50 and 0.02 to 0.21 for the HSF1 and the HSPA6 genes, respectively. Overall, almost all SNP analyzed showed significant deviation from the Hardy-Weinberg Equilibrium and half of the loci had heterozygosity greater than 0.50. The data suggest that there is sequence variability in these genes that could be exploited by breeding programs. There is genetic variation in HSF1 and HSPA6 genes in this populations of Angus breed, which is fundamental to obtain response to selection. Made available in DSpace on 2019-02-20T00:36:33Z (GMT). No. of bitstreams: 1 10HSF1HSPA60functionalcandidate.pdf: 437465 bytes, checksum: 593fb679a2d5d89ae36fe912252e7655 (MD5) Previous issue date: 2019-02-19

Beef tenderness, a complex trait affected by many factors, is economically important to beef quality, industry, and consumer?s palatability. In this study, RNA-Seq was used in network analysis to better understand the biological processes that lead to differences in beef tenderness. Skeletal muscle transcriptional profiles from 24 Nellore steers, selected by extreme estimated breeding values (EBVs) for shear force after 14 days of aging, were analyzed and 22 differentially expressed transcripts were identified. Among these were genes encoding ribosomal proteins, glutathione transporter ATP-binding cassette, sub-family C (CFTR/MRP), member 4 (ABCC4), and synaptotagmin IV (SYT4). Complementary co-expression analyses using Partial Correlation with Information Theory (PCIT), Phenotypic Impact Factor (PIF) and the Regulatory Impact Factor (RIF) methods identified candidate regulators and related pathways. The PCIT analysis identified ubiquitin specific peptidase 2 (USP2), growth factor receptor-bound protein 10 (GBR10), anoctamin 1 (ANO1), and transmembrane BAX inhibitor motif containing 4 (TMBIM4) as the most differentially hubbed (DH) transcripts. The transcripts that had a significant correlation with USP2, GBR10, ANO1, and TMBIM4 enriched for proteasome KEGG pathway. RIF analysis identified microRNAs as candidate regulators of variation in tenderness, including bta-mir-133a-2 and bta-mir-22. Both microRNAs have target genes present in the calcium signaling pathway and apoptosis. PIF analysis identified myoglobin (MB), enolase 3 (ENO3), and carbonic anhydrase 3 (CA3) as potentially having fundamental roles in tenderness. Pathways identified in our study impacted in beef tenderness included: calcium signaling, apoptosis, and proteolysis. These findings underscore some of the complex molecular mechanisms that control beef tenderness in Nellore cattle. Made available in DSpace on 2019-02-20T00:35:57Z (GMT). No. of bitstreams: 1 8GeneCoexpressionAnalysis.pdf: 9628281 bytes, checksum: e29e4cd73ae532b854633fb4d1d788c8 (MD5) Previous issue date: 2019-02-19

Made available in DSpace on 2018-12-11T17:17:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-12-01 Bovine respiratory disease (BRD) is the most common infectious disease of beef and dairy cattle and is characterized by a complex infectious etiology that includes a variety of viral and bacterial pathogens. We examined the global changes in mRNA abundance in healthy lung and lung lesions and in the lymphoid tissues bronchial lymph node, retropharyngeal lymph node, nasopharyngeal lymph node and pharyngeal tonsil collected at the peak of clinical disease from beef cattle experimentally challenged with either bovine respiratory syncytial virus, infectious bovine rhinotracheitis, bovine viral diarrhea virus, Mannheimia haemolytica or Mycoplasma bovis. We identified signatures of tissue-specific transcriptional responses indicative of tropism in the coordination of host's immune tissue responses to infection by viral or bacterial infections. Furthermore, our study shows that this tissue tropism in host transcriptional response to BRD pathogens results in the activation of different networks of response genes. The differential crosstalk among genes expressed in lymphoid tissues was predicted to be orchestrated by specific immune genes that act as 'key players' within expression networks. The results of this study serve as a basis for the development of innovative therapeutic strategies and for the selection of cattle with enhanced resistance to BRD. Division of Animal Sciences University of Missouri Embrapa Southeast Livestock Departamento de Ciencias Exatas UNESP Univ Estadual Paulista Faculdade de Ciencias Agrarias e Veterinarias Department of Veterinary Pathobiology College of Veterinary Medicine Texas AandM University Informatics Institute University of Missouri Department of Pathology Microbiology and Immunology School of Veterinary Medicine University of California Department of Animal Science College of Agriculture University of California Department of Animal Sciences College of Agriculture Natural Resource Sciences Washington State University Departamento de Ciencias Exatas UNESP Univ Estadual Paulista Faculdade de Ciencias Agrarias e Veterinarias

Made available in DSpace on 2018-11-26T15:44:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-06-01 EMBRAPA Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Nelore is the most economically important cattle breed in Brazil, and the use of genetically improved animals has contributed to increased beef production efficiency. The Brazilian beef feedlot industry has grown considerably in the last decade, so the selection of animals with higher growth rates on feedlot has become quite important. Genomic selection (GS) could be used to reduce generation intervals and improve the rate of genetic gains. The aim of this study was to evaluate the prediction of genomic-estimated breeding values (GEBV) for average daily weight gain (ADG) in 718 feedlot-finished Nelore steers. Analyses of three Bayesian model specifications [Bayesian GBLUP (BGBLUP), BayesA, and BayesC pi] were performed with four genotype panels [Illumina BovineHD BeadChip, TagSNPs, and GeneSeek High-and Low-density indicus (HDi and LDi, respectively)]. Estimates of Pearson correlations, regression coefficients, and mean squared errors were used to assess accuracy and bias of predictions. Overall, the BayesC pi model resulted in less biased predictions. Accuracies ranged from 0.18 to 0.27, which are reasonable values given the heritability estimates (from 0.40 to 0.44) and sample size (568 animals in the training population). Furthermore, results from Bos taurus indicus panels were as informative as those from Illumina BovineHD, indicating that they could be used to implement GS at lower costs. Univ Estadual Paulista, Fac Ciencias Agr & Vet, Via Acesso Prof Paulo Donato Castellane, BR-14884900 Jaboticabal, Brazil Embrapa Pecuaria Sudeste, BR-13560970 Sao Carlos, SP, Brazil Univ Wisconsin, Dept Anim Sci, Madison, WI 53706 USA Univ Fed Sao Carlos, Dept Genet & Evolucao, BR-13565905 Sao Carlos, SP, Brazil Univ Sao Paulo, Dept Zootecnia, BR-13418900 Piracicaba, Brazil Univ Estadual Paulista, Fac Ciencias Agr & Vet, Via Acesso Prof Paulo Donato Castellane, BR-14884900 Jaboticabal, Brazil FAPESP: 2012/23702-8 FAPESP: 2013/21644-3 FAPESP: 2012/23638-8

Made available in DSpace on 2018-12-11T17:14:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-08-23 Background: Beef cattle breeding programs in Brazil have placed greater emphasis on the genomic study of reproductive traits of males and females due to their economic importance. In this study, genome-wide associations were assessed for scrotal circumference at 210d of age, scrotal circumference at 420d of age, age at first calving, and age at second calving, in Canchim beef cattle. Data quality control was conducted resulting in 672,778 SNPs and 392 animals. Results: Associated SNPs were observed for scrotal circumference at 420d of age (435 SNPs), followed by scrotal circumference at 210d of age (12 SNPs), age at first calving (six SNPs), and age at second calving (four SNPs). We investigated whether significant SNPs were within genic or surrounding regions. Biological processes of genes were associated with immune system, multicellular organismal process, response to stimulus, apoptotic process, cellular component organization or biogenesis, biological adhesion, and reproduction. Conclusions: Few associations were observed for scrotal circumference at 210d of age, age at first calving, and age at second calving, reinforcing their polygenic inheritance and the complexity of understanding the genetic architecture of reproductive traits. Finding many associations for scrotal circumference at 420d of age in various regions of the Canchim genome also reveals the difficulty of targeting specific candidate genes that could act on fertility; nonetheless, the high linkage disequilibrium between loci herein estimated could aid to overcome this issue. Therefore, all relevant information about genomic regions influencing reproductive traits may contribute to target candidate genes for further investigation of causal mutations and aid in future genomic studies in Canchim cattle to improve the breeding program. Universidade Federal da Paraíba (UFPB) Departamento de Zootecnia Fast Genetics Beef Improvement Opportunities (BIO) University of Guelph Centre for Genetic Improvement of Livestock (CGIL) Department of Animal and Poultry Science Universidade Estadual Paulista (Unesp) Departamento de Ciências Exatas Faculdade de Ciências Agrárias e Veterinárias Universidade Estadual Paulista (Unesp) Departamento de Zootecnia Núcleo de Pesquisa e Conservação de Cervídeos Faculdade de Ciências Agrárias e Veterinárias Federal University of Lavras (UFLA) Department of Animal Science Federal University of São Carlos (UFSCar) Department of Genetics and Evolution Embrapa Agricultural Informatics Embrapa Dairy Cattle Embrapa Southeast Livestock Universidade Estadual Paulista (Unesp) Departamento de Ciências Exatas Faculdade de Ciências Agrárias e Veterinárias Universidade Estadual Paulista (Unesp) Departamento de Zootecnia Núcleo de Pesquisa e Conservação de Cervídeos Faculdade de Ciências Agrárias e Veterinárias

The objectives of this study were to characterize the allelic and genotypic frequencies of polymorphisms in the μ-calpain and calpastatin genes, and to assess their association with meat tenderness and animal growth in Nellore cattle. We evaluated 605 Nellore animals at 24 months of age, on average, at slaughter. The polymorphisms were determined for the molecular markers CAPN316, CAPN530, CAPN4751, CAPN4753, and UOGACAST1. Analyses of meat tenderness at 7, 14, and 21 days of maturation were performed in samples of longissimus thoracis obtained between the 12th and 13th rib and sheared using a Warner Bratzler Shear Force. Significant effects were observed for meat tenderness at days 7, 14, and 21 of maturation for the marker CAPN4751, at day 21 for the marker CAPN4753, and at days 14 and 21 for the marker UOGCAST1. For genotypic combinations of markers, the results were significant for the combination CAPN4751/UOGCAST1 in the three maturation periods and CAPN4753/UOGCAST1 at days 14 and 21 of maturation. Made available in DSpace on 2019-05-22T01:09:01Z (GMT). No. of bitstreams: 1 gmr1601gmr.16018957.pdf: 419991 bytes, checksum: 0bc3a0a4a9b15ddc7a15ed42441370d9 (MD5) Previous issue date: 2017

Numerical approaches to high-density single nucleotide polymorphism (SNP) data are often employed independently to address individual questions. We linked independent approaches in a bioinformatics pipeline for further insight. The pipeline driven by heterozygosity and Hardy-Weinberg equilibrium (HWE) analyses was applied to characterize Bos taurus and Bos indicus ancestry. We infer a gene co-heterozygosity network that regulates bovine fertility, from data on 18,363 cattle with genotypes for 729,068 SNP. Hierarchical clustering separated populations according to Bos taurus and Bos indicus ancestry. The weights of the first principal component were subjected to Normal mixture modelling allowing the estimation of a gene's contribution to the Bos taurus-Bos indicus axis. We used deviation from HWE, contribution to Bos indicus content and association to fertility traits to select 1,284 genes. With this set, we developed a co-heterozygosity network where the group of genes annotated as fertility-related had significantly higher Bos indicus content compared to other functional classes of genes, while the group of genes associated with milk production had significantly higher Bos taurus content. The network analysis resulted in capturing novel gene associations of relevance to bovine domestication events. We report transcription factors that are likely to regulate genes associated with cattle domestication and tropical adaptation. Our pipeline can be generalized to any scenarios where population structure requires scrutiny at the molecular level, particularly in the presence of a priori set of genes known to impact a phenotype of evolutionary interest such as fertility. Made available in DSpace on 2018-02-01T23:36:44Z (GMT). No. of bitstreams: 1 APBostaurusPlosOne.pdf: 4208873 bytes, checksum: cc037124470b280aaa27de1136e41635 (MD5) Previous issue date: 2018-02-01 Artigo e0181930. Na publicação: Mauricio A. Mudadu, Luciana Regitano.

Residual feed intake (RFI), a measure of feed efficiency (FE), is defined as the difference between the observed and the predictable feed intake considering size and growth of the animal. It is extremely important to beef production systems due to its impact on the allocation of land areas to alternative agricultural production, animal methane emissions, food demand and cost of production. Global differential gene expression analysis between high and low RFI groups (HRFI and LRFI: less and more efficient, respectively) revealed 73 differentially expressed (DE) annotated genes in Longissimus thoracis (LT) muscle of Nelore steers. These genes are involved in the overrepresented pathways Metabolism of Xenobiotics by Cytochrome P450 and Butanoate and Tryptophan Metabolism. Among the DE transcripts were several proteins related to mitochondrial function and the metabolism of lipids. Our findings indicate that observed gene expression differences are primarily related to metabolic processes underlying oxidative stress. Genes involved in the metabolism of xenobiotics and antioxidant mechanisms were primarily down-regulated, while genes responsible for lipid oxidation and ketogenesis were up-regulated in HRFI group. By using LT muscle, this study reinforces our previous findings using liver tissue and reveals new genes and likely tissue-specific regulators playing key-roles in these processes. Made available in DSpace on 2019-06-15T00:40:16Z (GMT). No. of bitstreams: 1 srep39493.pdf: 952515 bytes, checksum: 9755372b27a1436f18494890258e8707 (MD5) Previous issue date: 2016

Made available in DSpace on 2018-12-11T17:31:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-02-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The aim of this study was to evaluate the level of introgression of breeds in the Canchim (CA: 62.5% Charolais-37.5% Zebu) and MA genetic group (MA: 65.6% Charolais-34.4% Zebu) cattle using genomic information on Charolais (CH), Nelore (NE), and Indubrasil (IB) breeds. The number of animals used was 395 (CA and MA), 763 (NE), 338 (CH), and 37 (IB). The Bovine 50SNP BeadChip from Illumina panel was used to estimate the levels of introgression of breeds considering the Maximum likelihood, Bayesian, and Single Regression method. After genotype quality control, 32,308 SNPs were considered in the analysis. Furthermore, three thresholds to prune out SNPs in linkage disequilibrium higher than 0.10, 0.05, and 0.01 were considered, resulting in 15,286, 7,652, and 1,582 SNPs, respectively. For k = 2, the proportion of taurine and indicine varied from the expected proportion based on pedigree for all methods studied. For k = 3, the Regression method was able to differentiate the animals in three main clusters assigned to each purebred breed, showing more reasonable according to its biological viewpoint. Analyzing the data considering k = 2 seems to be more appropriate for Canchim-MA animals due to its biological interpretation. The usage of 32,308 SNPs in the analyses resulted in similar findings between the estimated and expected breed proportions. Using the Regression approach, a contribution of Indubrasil was observed in Canchim-MA when k = 3 was considered. Genetic parameter estimation could account for this breed composition information as a source of variation in order to improve the accuracy of genetic models. Our findings may help assemble appropriate reference populations for genomic prediction for Canchim-MA in order to improve prediction accuracy. Using the information on the level of introgression in each individual could also be useful in breeding or crossing design to improve individual heterosis in crossbred cattle. Departamento de Ci�ncias Exatas Universidade Estadual Paulista (Unesp) Faculdade de Ci�ncias Agrarias e Veterinarias Beef Improvement Opportunities (BIO) Departamento de Ci�ncias Basicas Universidade de S�o Paulo (USP) Faculdade de Zootecnia e Engenharia de Alimentos (FZEA) Departamento de Zootecnia Universidade Estadual Paulista (Unesp) Faculdade de Ci�ncias Agrarias e Veterinarias Embrapa Southeast Livestock Embrapa Agricultural Informatics Faculdade de Agronomia e Medicina Veterin�ria Universidade de Passo Fundo Embrapa Dairy Cattle Department of Agricultural Food and Nutritional Science University of Alberta Lacombe Research and Development Centre Agriculture and Agri-Food Canada, 6000 C and E Trail Department of Animal and Poultry Science University of Guelph Centre for Genetic Improvement of Livestock (CGIL) Departamento de Ci�ncias Exatas Universidade Estadual Paulista (Unesp) Faculdade de Ci�ncias Agrarias e Veterinarias Departamento de Zootecnia Universidade Estadual Paulista (Unesp) Faculdade de Ci�ncias Agrarias e Veterinarias CAPES: 02663/09-0 CNPq: 449564/2014-2

Iron (Fe) is an essential mineral for metabolism and plays a central role in a range of biochemical processes. Therefore, this study aimed to identify differentially expressed (DE) genes and metabolic pathways in Longissimus dorsi (LD) muscle from cattle with divergent iron content, as well as to investigate the likely role of these DE genes in biological processes underlying beef quality parameters. Samples for RNA extraction for sequencing and iron, copper, manganese, and zinc determination were collected from LD muscles at slaughter. Eight Nelore steers, with extreme genomic estimated breeding values for iron content (Fe-GEBV), were selected from a reference population of 373 animals. From the 49 annotated DE genes (FDR

Feed efficiency and carcass characteristics are late-measured traits. The detection of molecular markers associated with them can help breeding programs to select animals early in life, and to predict breeding values with high accuracy. The objective of this study was to identify polymorphisms in the functional and positional candidate gene NEUROD1 (neurogenic differentiation 1), and investigate their associations with production traits in reference families of Nelore cattle. A total of 585 steers were used, from 34 sires chosen to represent the variability of this breed. By sequencing 14 animals with extreme residual feed intake (RFI) values, seven single nucleotide polymorphisms (SNPs) in NEUROD1 were identified. The investigation of marker effects on the target traits RFI, backfat thickness (BFT), ribeye area (REA), average body weight (ABW), and metabolic body weight (MBW) was performed with a mixed model using the restricted maximum likelihood method. SNP1062, which changes cytosine for guanine, had no significant association with RFI or REA. However, we found an additive effect on ABW (P ≤ 0.05) and MBW (P ≤ 0.05), with an estimated allele substitution effect of -1.59 and -0.93 kg0.75, respectively. A dominant effect of this SNP for BFT was also found (P ≤ 0.010). Our results are the first that identify NEUROD1 as a candidate that affects BFT, ABW, and MBW. Once confirmed, the inclusion of this SNP in dense panels may improve the accuracy of genomic selection for these traits in Nelore beef cattle as this SNP is not currently represented on SNP chips. Made available in DSpace on 2019-03-29T00:30:01Z (GMT). No. of bitstreams: 1 mudadugmr2016.pdf: 362528 bytes, checksum: c9a8442e6945b6e351679c59fe28aa38 (MD5) Previous issue date: 2016

Brazil is one of the largest beef producers and exporters in the world with the Nelore breed representing the vast majority of Brazilian cattle (Bos taurus indicus). Despite the great adaptability of the Nelore breed to tropical climate, meat tenderness (MT) remains to be improved. Several factors including genetic composition can influence MT. In this article, we report a genome-wide analysis of copy number variation (CNV) inferred from Illumina1 High Density SNP-chip data for a Nelore population of 723 males. We detected >2,600 CNV regions (CNVRs) representing 6.5% of the genome. Comparing our results with previous studies revealed an overlap in 1400 CNVRs (>50%). A total of 1,155 CNVRs (43.6%) overlapped 2,750 genes. They were enriched for processes involving guanosine triphosphate (GTP), previously reported to influence skeletal muscle physiology and morphology. Nelore CNVRs also overlapped QTLs for MT reported in other breeds (8.9%, 236 CNVRs) and from a previous study with this population (4.1%, 109 CNVRs). Two CNVRs were also proximal to glutathione metabolism genes that were previously associated with MT. Genome-wide association study of CN state with estimated breeding values derived from meat shear force identified 6 regions, including a region on BTA3 that contains genes of the cAMP and cGMP pathway. Ten CNVRs that overlapped regions associated with MT were successfully validated by qPCR. Our results represent the first comprehensive CNV study in Bos taurus indicus cattle and identify regions in which copy number changes are potentially of importance for the MT phenotype. Made available in DSpace on 2019-04-02T00:31:48Z (GMT). No. of bitstreams: 1 pone.0157711.pdf: 1881794 bytes, checksum: 295c01f8a4b9690dd3bf6d9a3eff9c5f (MD5) Previous issue date: 2016

Made available in DSpace on 2019-04-10T00:39:26Z (GMT). No. of bitstreams: 1 GENESDIFERENCIALMENTEEXPRESSOSEMMUSCULODENOVILHOSNELOREDIVERGENTESPARAEFICIENCIAPARCIALDECRESCIMENTO.pdf: 392032 bytes, checksum: 040cb26c1f45b894cb4a670fc93a7ece (MD5) Previous issue date: 2016

Background Lipids are a class of molecules that play an important role in cellular structure and metabolism in all cell types. In the last few decades, it has been reported that long-chain fatty acids (FAs) are involved in several biological functions from transcriptional regulation to physiological processes. Several fatty acids have been both positively and negatively implicated in different biological processes in skeletal muscle and other tissues. To gain insight into biological processes associated with fatty acid content in skeletal muscle, the aim of the present study was to identify differentially expressed genes (DEGs) and functional pathways related to gene expression regulation associated with FA content in cattle. Results Skeletal muscle transcriptome analysis of 164 Nellore steers revealed no differentially expressed genes (DEGs, FDR 10%) for samples with extreme values for linoleic acid (LA) or stearic acid (SA), and only a few DEGs for eicosapentaenoic acid (EPA, 5 DEGs), docosahexaenoic acid (DHA, 4 DEGs) and palmitic acid (PA, 123 DEGs), while large numbers of DEGs were associated with oleic acid (OA, 1134 DEGs) and conjugated linoleic acid cis9 trans11 (CLA-c9t11, 872 DEGs). Functional annotation and functional enrichment from OA DEGs identified important genes, canonical pathways and upstream regulators such as SCD, PLIN5, UCP3, CPT1, CPT1B, oxidative phosphorylation mitochondrial dysfunction, PPARGC1A, and FOXO1. Two important genes associated with lipid metabolism, gene expression and cancer were identified as DEGs between animals with high and low CLA-c9t11, specifically, epidermal growth factor receptor (EGFR) and RNPS. Conclusion Only two out of seven classes of molecules of FA studied were associated with large changes in the expression profile of skeletal muscle. OA and CLA-c9t11 content had significant effects on the expression level of genes related to important biological processes associated with oxidative phosphorylation, and cell growth, survival, and migration. These results contribute to our understanding of how some FAs modulate metabolism and may have protective health function. Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-3306-x) contains supplementary material, which is available to authorized users.

In contrast to the Mendelian inheritance model, parental alleles can contribute unequally to gene expression, which may result in phenotypic variance among individuals and bias in the predicted additive effect of molecular markers associated with production traits. Given the need to understand the effects of allelic variation and parent-of-origin effects on the expression of genes with a commercial interest in cattle, we analyzed the expression of KCNJ11 (potassium inwardly rectifying channel, subfamily J, member 11), which was previously described as a functional candidate gene for meat tenderness. Allele-specific and parent-of-origin-dependent expression of this gene were assessed in bovine muscle using the rs379610823 single nucleotide polymorphism as a reference. Biallelic expression was observed; however, the T allele was expressed at significantly higher levels than the C allele. Furthermore, increased expression of KCNJ11 was found in animals harboring the maternal T allele. This study is the first to describe the differential allelic expression of bovine KCNJ11. Our findings are important for understanding the mechanisms that underlie the pattern of KCNJ11 expression and its potential impact on the phenotypic variation of meat tenderness in Nelore beef cattle. This reinforces the need for further investigation of allelic- and parent-of-origin expression deviation in genetic markers eligible for the selection of target traits.

Investigation of molecular marker effects on production traits is essential to define marker assisted selection strategies in beef cattle. We looked for a possible association of molecular markers and backfat thickness (BFT) and rib eye area (REA) in Canchim (5/8 Charolais + 3/8 Zebu) and MA (offspring of Charolais bulls and 1/2 Canchim + 1/2 Zebu cows) animals raised exclusively on pasture. Traits were measured on 987 individuals from seven herds from two Brazilian States (São Paulo and Goiás), in March and April from 2005 to 2007, when animals were, on average, 19 months of age. Five microsatellite markers lying in QTL regions for BFT and REA (BMS490 and ETH10 on chromosome 5, INRA133 and ILSTS090 on chromosome 6, and BMS2142 on chromosome 19) were genotyped and association analyses were performed under an animal model using the restricted Candidate gene region for control of rib eye area maximum likelihood method. After correction for multiple tests, a significant effect of microsatellite BMS490 on REA was observed, suggesting that at least one QTL affecting carcass traits in this region of the BTA5. No significant effect on BFT was observed for these markers. Made available in DSpace on 2022-07-28T18:35:59Z (GMT). No. of bitstreams: 1 gmr1175.pdf: 387982 bytes, checksum: 01ffb00d40063ac120206b31ab919f13 (MD5) Previous issue date: 2011

Made available in DSpace on 2018-12-11T17:02:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-05-05 Background: Recent technological advances in genomics have allowed the genotyping of cattle through single nucleotide polymorphism (SNP) panels. High-density SNP panels possess greater genome coverage and are useful for the identification of conserved regions of the genome due to selection, known as selection signatures (SS). The SS are detectable by different methods, such as the extended haplotype homozygosity (EHH); and the integrated haplotype score (iHS), which is derived from the EHH. The aim of this study was to identify SS regions in Canchim cattle (composite breed), genotyped with high-density SNP panel. Results: A total of 687,655 SNP markers and 396 samples remained for SS analysis after the genotype quality control. The iHS statistic for each marker was transformed into piHS for better interpretation of the results. Chromosomes BTA5 and BTA14 showed piHS > 5, with 39 and nine statistically significant SNPs (P < 0.00001), respectively. For the candidate selection regions, iHS values were computed across the genome and averaged within non-overlapping windows of 500 Kb. We have identified genes that play an important role in metabolism, melanin biosynthesis (pigmentation), and embryonic and bone development. Conclusions: The observation of SS indicates that the selection processes performed in Canchim, as well as in the founder breeds (i.e. Charolais), are maintaining specific genomic regions, particularly on BTA5 and BTA14. These selection signatures regions could be associated with Canchim characterization. Univ Estadual Paulista Faculdade de Ciências Agrárias e Veterinárias Departamento de Ciências Exatas UNESP - Univ Estadual Paulista Faculdade de Ciências Agrárias e Veterinárias Departamento de Tecnologia Embrapa Agricultural Informatics Embrapa Southeast Livestock Univ Estadual Paulista Faculdade de Ciências Agrárias e Veterinárias Departamento de Ciências Exatas UNESP - Univ Estadual Paulista Faculdade de Ciências Agrárias e Veterinárias Departamento de Tecnologia

Made available in DSpace on 2015-10-21T20:36:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-03-25. Added 1 bitstream(s) on 2015-10-22T09:47:55Z : No. of bitstreams: 1 WOS000351994200001.pdf: 1431968 bytes, checksum: b7029239d0376eb8d710b1b564138694 (MD5) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Agriculture and Food Research Initiative Background: Efficiency of feed utilization is important for animal production because it can reduce greenhouse gas emissions and improve industry profitability. However, the genetic basis of feed utilization in livestock remains poorly understood. Recent developments in molecular genetics, such as platforms for genome-wide genotyping and sequencing, provide an opportunity to identify genes and pathways that influence production traits. It is known that transcriptional networks influence feed efficiency-related traits such as growth and energy balance. This study sought to identify differentially expressed genes in animals genetically divergent for Residual Feed Intake (RFI), using RNA sequencing methodology (RNA-seq) to obtain information from genome-wide expression profiles in the liver tissues of Nelore cattle.Results: Differential gene expression analysis between high Residual Feed Intake (HRFI, inefficient) and low Residual Feed Intake (LRFI, efficient) groups was performed to provide insights into the molecular mechanisms that underlie feed efficiency-related traits in beef cattle. A total of 112 annotated genes were identified as being differentially expressed between animals with divergent RFI phenotypes. These genes are involved in ion transport and metal ion binding; act as membrane or transmembrane proteins; and belong to gene clusters that are likely related to the transport and catalysis of molecules through the cell membrane and essential mechanisms of nutrient absorption. Genes with functions in cellular signaling, growth and proliferation, cell death and survival were also differentially expressed. Among the over-represented pathways were drug or xenobiotic metabolism, complement and coagulation cascades, NRF2-mediated oxidative stress, melatonin degradation and glutathione metabolism.Conclusions: Our data provide new insights and perspectives on the genetic basis of feed efficiency in cattle. Some previously identified mechanisms were supported and new pathways controlling feed efficiency in Nelore cattle were discovered. We potentially identified genes and pathways that play key roles in hepatic metabolic adaptations to oxidative stress such as those involved in antioxidant mechanisms. These results improve our understanding of the metabolic mechanisms underlying feed efficiency in beef cattle and will help develop strategies for selection towards the desired phenotype. University of Missouri Columbia, Division of Animal Sciences Universidade de São Paulo, Departamento de Zootecnia, Escola Superior de Agricultura Luiz de Queiroz Universidade Federal de São Carlos, Departamento de Genética e Evolução Universidade Estadual Paulista, Departamento de Zootecnia, Faculdade de Ciências Agrárias e Veterinárias de Jaboticabal CNPq: 473091/2012-7 FAPESP: 2013/17778-4 FAPESP: 2014/13555-3 Agriculture and Food Research Initiative: 2011-68004-30214 Agriculture and Food Research Initiative: 2011-68004-30367 Agriculture and Food Research Initiative: 2013-68004-20364