Miguel Henrique de Almeida Santana

Genome-wide association analysis of feed intake and residual feed intake in Nellore cattle

BackgroundFeed intake plays an important economic role in beef cattle, and is related with feed efficiency, weight gain and carcass traits. However, the phenotypes collected for dry matter intake and feed efficiency are scarce when compared with other measures such as weight gain and carcass traits. The use of genomic information can improve the power of inference of studies on these measures, identifying genomic regions that affect these phenotypes. This work performed the genome-wide association study (GWAS) for dry matter intake (DMI) and residual feed intake (RFI) of 720 Nellore cattle (Bos taurus indicus).ResultsIn general, no genomic region extremely associated with both phenotypic traits was observed, as expected for the variables that have their regulation controlled by many genes. Three SNPs surpassed the threshold for the Bonferroni multiple test for DMI and two SNPs for RFI. These markers are located on chromosomes 4, 8, 14 and 21 in regions near genes regulating appetite and ion transport and close to important QTL as previously reported to RFI and DMI, thus corroborating the literature that points these two processes as important in the physiological regulation of intake and feed efficiency.ConclusionsThis study showed the first GWAS of DMI to identify genomic regions associated with feed intake and efficiency in Nellore cattle. Some genes and QTLs previously described for DMI and RFI, in other subspecies (Bos taurus taurus), that influences these phenotypes are confirmed in this study.

Liver transcriptomic networks reveal main biological processes associated with feed efficiency in beef cattle

BackgroundThe selection of beef cattle for feed efficiency (FE) traits is very important not only for productive and economic efficiency but also for reduced environmental impact of livestock. Considering that FE is multifactorial and expensive to measure, the aim of this study was to identify biological functions and regulatory genes associated with this phenotype.ResultsEight genes were differentially expressed between high and low feed efficient animals (HFE and LFE, respectively). Co-expression analyses identified 34 gene modules of which 4 were strongly associated with FE traits. They were mainly enriched for inflammatory response or inflammation-related terms. We also identified 463 differentially co-expressed genes which were functionally enriched for immune response and lipid metabolism. A total of 8 key regulators of gene expression profiles affecting FE were found. The LFE animals had higher feed intake and increased subcutaneous and visceral fat deposition. In addition, LFE animals showed higher levels of serum cholesterol and liver injury biomarker GGT. Histopathology of the liver showed higher percentage of periportal inflammation with mononuclear infiltrate.ConclusionLiver transcriptomic network analysis coupled with other results demonstrated that LFE animals present altered lipid metabolism and increased hepatic periportal lesions associated with an inflammatory response composed mainly by mononuclear cells. We are now focusing to identify the causes of increased liver lesions in LFE animals.

Protein synthesis and degradation gene SNPs related to feed intake, feed efficiency, growth, and ultrasound carcass traits in Nellore cattle.

We looked for possible associations of SNPs in genes related to protein turnover, with growth, feed efficiency and carcass traits in feedlot Nellore cattle. Purebred Nellore bulls and steers (N = 290; 378 ± 42 kg body weight, 23 months ± 42 days old) were evaluated for daily feed intake, body weight gain (BWG), gross feed efficiency, feed conversion ratio, partial efficiency of growth, residual feed intake (RFI), ultrasound backfat, rump fat, and ribeye area. Genotypes were obtained for SNPs in the growth hormone receptor (GHR-1 and GHR-2); calpain (CAPN4751); calpastatin (UoGCAST); ubiquitin-conjugating enzyme 2I (UBE2I-1 and UBE2I-2); R3H domain containing 1 (R3HDM1-1, -2, -3, and -4), ring finger protein 19 (RNF19); proteasome 26S subunit, non-ATPase, 13 (PSMD13); ribosomal protein, large, P2 (RPLP2); and isoleucine-tRNA synthetase 2, mitochondrial (IARS2) genes. Allelic substitution, additive and dominant effects were tested and molecular breeding values were computed. CAPN4751, GHR-1 and -2, IARS2, R3HDM1-4, and UoGCAST were found to be normally segregating polymorphisms. Additive and dominance effects were observed on BWG, feed efficiency and carcass traits, although dominant effects predominated. Significant allelic substitution effects were observed for CAPN4751, GHR-1 and -2, and UoGCAST on BWG, gross feed efficiency, RFI, and carcass traits, under single- or multiple-marker analyses. Correlations between molecular breeding values and phenotypes were low, excepted for RFI, based on allelic substitution estimates obtained by stepwise linear regression. We conclude that SNPs in genes related to protein turnover are related to economically important traits in Nellore cattle.

Blood cell and metabolic profile of Nellore bulls and their correlations with residual feed intake and feed conversion ratio

Em funcao das diversas variacoes metabolicas relacionadas com o consumo alimentar residual (CAR), objetivou-se nesse estudo avaliar as correlacoes do CAR tradicional (CAR1), CAR ajustado para deposicao de gordura subcutânea na garupa (CAR2) e da conversao alimentar (CA) com o perfil metabolico e sanguineo, assim como verificar as possiveis diferencas das classes de CAR1 e CAR2. Para tanto, foram utilizados 46 touros da raca Nelore com 22 meses de idade e 411kg no inicio do estudo. Os animais foram alimentados com a mesma dieta durante 84 dias, nesse periodo foram coletadas a cada 21 dias amostras de sangue para avaliacao de metabolitos no soro e do perfil celular no sangue. Nao foram encontradas correlacoes significativas da CA com nenhuma caracteristica metabolica ou sanguinea, ja para o CAR1 foi encontrada correlacao significativa para a concentracao de ureia serica, tambem houve diferenca entre as classes com relacao a creatinina, na qual animais mais eficientes apresentaram valores superiores para essa variavel. O CAR2 nao foi correlacionado com nenhuma variavel metabolica e das celulas do sangue, porem animais de menor CAR2 tiveram menor quantidade de eosinofilos quando comparados com os animais de maior CAR2. Esses resultados sugerem que animais menos eficientes para CAR podem ter maior gasto energetico com processos de sintese e degradacao proteica corporal, devido a maior quantidade de ureia presente no sangue.

A genomewide association mapping study using ultrasound-scanned information identifies potential genomic regions and candidate genes affecting carcass traits in Nellore cattle.

The aim of this study was to identify candidate genes and genomic regions associated with ultrasound-derived measurements of the rib-eye area (REA), backfat thickness (BFT) and rumpfat thickness (RFT) in Nellore cattle. Data from 640 Nellore steers and young bulls with genotypes for 290 863 single nucleotide polymorphisms (SNPs) were used for genomewide association mapping. Significant SNP associations were explored to find possible candidate genes related to physiological processes. Several of the significant markers detected were mapped onto functional candidate genes including ARFGAP3, CLSTN2 and DPYD for REA; OSBPL3 and SUDS3 for BFT; and RARRES1 and VEPH1 for RFT. The physiological pathway related to lipid metabolism (CLSTN2, OSBPL3, RARRES1 and VEPH1) was identified. The significant markers within previously reported QTLs reinforce the importance of the genomic regions, and the other loci offer candidate genes that have not been related to carcass traits in previous investigations.

Bovine NR1I3 gene polymorphisms and its association with feed efficiency traits in Nellore cattle

Abstract The Nuclear receptor 1 family I member 3 (NR1I3), also known as the Constitutive Androstane Receptor (CAR), was initially characterized as a key regulator of xenobiotic metabolism. However, recent biochemical and structural data suggest that NR1I3 is activated in response to metabolic and nutritional stress in a ligand-independent manner. Thus, we prospected the Bovine NR1I3 gene for polymorphisms and studied their association with feed efficiency traits in Nellore cattle. First, 155 purebred Nellore bulls were individually measured for Residual Feed Intake (RFI) and the 25 best (High Feed Efficiency group, HFE) and the 25 worst animals (Low Feed Efficiency group, LFE) were selected for DNA extraction. The entire Bovine NR1I3 gene was amplified and polymorphisms were identified by sequencing. Then, one SNP different between HFE and LFE groups was genotyped in all the 155 animals and in another 288 animals totalizing 443 Nellore bulls genotyped for association of NR1I3 SNPs with feed efficiency traits. We found 24 SNPs in the NR1I3 gene and choose a statistically different SNP between HFE and LFE groups for further analysis. Genotyping of the 155 animals showed a significant association within SNP and RFI (p = 0.04), Residual Intake and BW Gain (p = 0.04) and Dry Matter Intake (p = 0.01). This SNP is located in the 5′flanking promoter region of NR1I3 gene and different alleles alter the binding site for predicted transcriptional factors as HNF4alpha, CREM and c-MYB, leading us to conclude that NR1I3 expression and regulation might be important to feed efficiency.

Residual feed intake and hematological and metabolic blood profiles of lle de France lambs

The objectives of this study were to estimate the phenotypic correlations of residual feed intake (RFI) and gross feed efficiency (GFE) with hematological and metabolic blood profiles of lambs and to determine the differences for these traits in animals of different RFI classes. Twenty Ile de France male lambs, 115±8 days of age and 31.3±4.1 kg of body weight (means ± SD), were individually housed and their dry matter intake was measured over 65 days. They were weighed every 13 days to determine the average daily weight gain and two blood samples were collected at the last two weighings (at 07h30) for analysis of blood variables. The animals were divided into two classes: negative RFI (most efficient: 0.5 SD above the mean; n=8). There were associations among RFI and the serum metabolic variables for albumin (rRFI = 0.74) and creatinine (rRFI = -0.45) and between GFE and serum albumin (rGFE = -0.70). Less efficient animals as measured by RFI had higher serum albumin and lower creatinine levels and showed a tendency to have a greater concentration of total plasma protein. Other serum biochemical parameters were not correlated with GFE and RFI, and no differences between RFI classes were found. There was a correlation between the percentage of eosinophils and RFI (rRFI = -0.65), and such more efficient animals had a higher proportion of these cells and a trend to have a lower percentage of monocytes. This study provided evidence indicating associations between RFI and protein metabolism, as reflected by the serum albumin and creatinine. The hematological findings suggest that RFI is related to susceptibility of lambs to stressand should provide a basis for further research in this regard.

Visual body-scores selection and its influence on body size and ultrasound carcass traits in Nellore cattle

Genetic parameters, genetic trends, and genetic progress of carcass traits were estimated for 12,447 Nellore individuals from different Brazilian herds. The following carcass traits were analyzed: visual body scores of conformation (CONF), precocity (PREC), and muscularity (MUSC); rump width (RW) and rump length (RL), body size (frame); and ultrasound evaluation of ribeye area (REA), backfat thickness (BFT), and rump fat thickness (RFT). Heritability estimates (± SE) for CONF, PREC, and MUSC were 0.23 ± 0.02, 0.33 ± 0.03, and 0.31 ± 0.02, respectively. The heritability estimates (± SE) for RW, RL, and frame were 0.25 ± 0.05, 0.16 ± 0.04, and 0.31 ± 0.03, respectively. Ultrasound of the REA, BFT, and RFT presented mean heritability estimates (± SE) of 0.38 ± 0.03, 0.44 ± 0.04, and 0.47 ± 0.04, respectively. The visual body score of CONF had high genetic correlations with RW, RL, and frame (0.74 ± 0.09, 0.82 ± 0.08, and 0.83 ± 0.04, respectively), indicating a high association of CONF with the measurements related to body structure. The REA had no correlation with BFT and RFT (-0.09 ± 0.04 and -0.03 ± 0.04, respectively) and showed only a moderate genetic correlation with MUSC (0.39 ± 0.05). The BFT and RFT had moderate genetic correlations with PREC (0.36 ± 0.07 and 0.29 ± 0.07, respectively) and no correlation with frame (-0.02 ± 0.03 and 0.05 ± 0.05, respectively), suggesting that selection for frame had no effect on the subcutaneous fat content of the carcass. Low genetic trends and low genetic progress were obtained for REA (0.026 cm, 0.02%), BFT (0.0031 mm, 0.05%), and RFT (0.0013 mm, 0.02%), with no significant values of genetic progress detected throughout the studied period. The CONF, PREC, and MUSC presented high genetic trends (0.030 points, 0.030 points, and 0.029 points, respectively) and high genetic progress (0.60%, 0.56%, and 0.59%, respectively), indicating a significant genetic progress for these traits throughout the evaluated period. Carcass traits evaluated by ultrasound and visual body scores are eligible for selection and can be used in genetic improvement programs in Nellore cattle; however, visual body score selection for carcass traits can result in slower genetic progress for carcass quality when compared to selection performed by ultrasound.

Systems genetics and genome-wide association approaches for analysis of feed intake, feed efficiency, and performance in beef cattle

Feed intake, feed efficiency, and weight gain are important economic traits of beef cattle in feedlots. In the present study, we investigated the physiological processes underlying such traits from the point of view of systems genetics. Firstly, using data from 1334 Nellore (Bos indicus) cattle and 943,577 single nucleotide polymorphisms (SNPs), a genome-wide association analysis was performed for dry matter intake, average daily weight gain, feed conversion ratio, and residual feed intake with a Bayesian Lasso procedure. Genes within 50-kb SNPs, most relevant for explaining the genomic variance, were annotated and the biological processes underlying the traits were inferred from Database for Annotation, Visualization and Integrated Discovery (DAVID) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Our results indicated several putative genomic regions associated with the target phenotypes and showed that almost all genomic variances were in the SNPs located in the intergenic and intronic regions. We further identified five main metabolic pathways related to ion transport, body composition, and feed intake control, which influenced the four phenotypes simultaneously. The systems genetics approach used in this study revealed novel pathways related to feed efficiency traits in beef cattle.

Genome-wide association with residual body weight gain in Bos indicus cattle

Weight gain is a key performance trait for beef cat-tle; however, attention should be given to the production costs for better profitability. Therefore, a feed efficiency trait based on per-formance can be an interesting approach to improve performance without increasing food costs. To identify candidate genes and ge-nomic regions associated with residual body weight gain (RWG), we conducted a genome-wide association study (GWAS) with 720 Nellore cattle using the GRAMMAR-Gamma association test. We identified 30 significant single nucleotide polymorphisms (SNPs), especially on chromosomes 2, 8, 12, and 17. Several genes and quantitative train loci (QTLs) present in the regions identified were appointed; we highlight DMRT2 (doublesex and mab-3 related tran-scription factor 2), IFFO2 (intermediate filament family orphan 2), LNX2 (ligand of numb-protein X 2), MTIF3 (mitochondrial transla-tional initiation factor 3), and TRNAG-CCC (transfer RNA glycine anticodon CCC). The metabolic pathways that can explain part of the phenotypic variation in RWG are related to oxidative stress and muscle control.