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A major QTL for host response to porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) infection was identified in a previous study. Single nucleotide polymorphism WUR10000125 (WUR), which is in complete linkage disequilibrium with the putative causative mutation, can be used as a tag SNP for the QTL. However, the effect of WUR following PRRS vaccination and/or coinfection with other pathogens is not known. Therefore, objectives of this study were to estimate the effect of WUR on host response following PRRS vaccination and coinfection of PRRSV with porcine circovirus type 2b (PCV2b), to estimate genetic parameters for host response to vaccination and coinfection, and to estimate the effect of previously identified candidate SNP under PRRSV-only or PCV2b-only infection on host response to coinfection. Data from 2 trials, comprising a total of 396 commercial crossbred nursery pigs from a single genetic source, were used for all analyses. Pigs were preselected based on WUR genotype: approximately half AA and half AB, where B is the favorable and dominant allele. At weaning, pigs were shipped to Kansas State University, where half of the pigs were vaccinated with a PRRS modified live virus vaccine. Four weeks later, all pigs were coinfected with field strains of PRRSV and PCV2b and followed for 42 d. Body weight and serum viremia measurements were collected following vaccination and coinfection to calculate ADG and viral load (VL), respectively. Average heritability estimates for PRRS VL, PCV2b VL, and ADG were 0.29, 0.09, and 0.40, respectively. After vaccination, AB pigs had lower vaccination VL ( = 0.03) and faster gain ( = 0.004) than AA pigs, as expected. After coinfection, AB pigs had lower PRRSV VL ( < 0.001) but did not significantly differ from AA pigs in growth rate ( = 0.86). For PCV2b VL, suggestive evidence of an interaction between vaccination and WUR genotype ( = 0.11) was detected, where AB pigs had significantly lower PCV2b VL when vaccinated ( = 0.007) but not when they were not vaccinated ( = 0.87). In addition to WUR, several PRRS-associated SNP and a PCV2b-associated SNP had significant effects on host response to coinfection. In conclusion, marker-assisted selection based on WUR genotype alone, or along with other candidate SNP for PRRSV and PCV2b infection, is a promising strategy to select for improved host response to not just PRRS but also coinfection of PRRSV with PCV2b and perhaps other pathogens.

Porcine reproductive and respiratory syndrome (PRRS) is a devastating disease in the swine industry. Identification of host genetic factors that enable selection for improved performance during PRRS virus (PRRSV) infection would reduce the impact of this disease on animal welfare and production efficiency. We conducted genomewide association study (GWAS) analyses of data from 13 trials of approximately 200 commercial crossbred nursery-age piglets that were experimentally infected with 1 of 2 type 2 isolates of PRRSV (NVSL 97-7985 [NVSL] and KS2006-72109 [KS06]). Phenotypes analyzed were viral load (VL) in blood during the first 21 d after infection (dpi) and weight gain (WG) from 0 to 42 dpi. We accounted for the previously identified QTL in the region on SSC4 in our models to increase power to identify additional regions. Many regions identified by single-SNP analyses were not identified using Bayes-B, but both analyses identified the same regions on SSC3 and SSC5 to be associated with VL in the KS06 trials and on SSC6 in the NVSL trials ( < 5 × 10); for WG, regions on SSC5 and SSC17 were associated in the NVSL trials ( < 3 × 10). No regions were identified with either method for WG in the KS06 trials. Except for the region on SSC4, which was associated with VL for both isolates (but only with WG for NVSL), identified regions did not overlap between the 2 PRRSV isolate data sets, despite high estimates of the genetic correlation between isolates for traits based on these data. We also identified genomic regions whose associations with VL or WG interacted with either PRRSV isolate or with genotype at the SSC4 QTL. Gene ontology (GO) annotation terms for genes located near moderately associated SNP ( < 0.003) were enriched for multiple immunologically (VL) and metabolism- (WG) related GO terms. The biological relevance of these regions suggests that, although it may increase the number of false positives, the use of single-SNP analyses and a relaxed threshold also increased the identification of true positives. In conclusion, although only the SSC4 QTL was associated with response to both PRRSV isolates, genes near associated SNP were enriched for the same GO terms across PRRSV isolates, suggesting that host responses to these 2 isolates are affected by the actions of many genes that function together in similar biological processes.

Background: Our recent research showed that antibody response to porcine reproductive and respiratory syndrome (PRRS), measured as sample-to-positive (S/P) ratio, is highly heritable and has a high genetic correlation with reproductive performance during a PRRS outbreak. Two major quantitative trait loci (QTL) on Sus scrofa chromosome 7 (SSC7; QTLMHC and QTL130) accounted for ~40 % of the genetic variance for S/P. Objectives of this study were to estimate genetic parameters for PRRS S/P in gilts during acclimation, identify regions associated with S/P, and evaluate the accuracy of genomic prediction of S/P across populations with different prevalences of PRRS and using different single nucleotide polymorphism (SNP) sets., Methods: Phenotypes and high-density SNP genotypes of female pigs from two datasets were used. The outbreak dataset included 607 animals from one multiplier herd, whereas the gilt acclimation (GA) dataset included data on 2364 replacement gilts from seven breeding companies placed on health-challenged farms. Genomic prediction was evaluated using GA for training and validation, and using GA for training and outbreak for validation. Predictions were based on SNPs across the genome (SNPAll), SNPs in one (SNPMHC and SNP130) or both (SNPSSC7) QTL, or SNPs outside the QTL (SNPRest)., Results: Heritability of S/P in the GA dataset increased with the proportion of PRRS-positive animals in the herd (from 0.28 to 0.47). Genomic prediction accuracies ranged from low to moderate. Average accuracies were highest when using only the 269 SNPs in both QTL regions (SNPSSC7, with accuracies of 0.39 and 0.31 for outbreak and GA validation datasets, respectively. Average accuracies for SNPALL, SNPMHC, SNP130, and SNPRest were, respectively, 0.26, 0.39, 0.21, and 0.05 for the outbreak, and 0.28, 0.25, 0.22, and 0.12, for the GA validation datasets., Conclusions: Moderate genomic prediction accuracies can be obtained for PRRS antibody response using SNPs located within two major QTL on SSC7, while the rest of the genome showed limited predictive ability. Results were obtained using data from multiple genetic sources and farms, which further strengthens these findings. Further research is needed to validate the use of S/P ratio as an indicator trait for reproductive performance during PRRS outbreaks.

The use of corn coproducts increases the concentration of fiber and, often, the use of supplemental lipids in swine diets, which may affect energy and nutrient digestibility. An experiment was conducted to determine the effects of reduced-oil distillers' dried grains with solubles (DDGS) and soybean oil (SBO) on dietary AA, acid hydrolyzed ether extract (AEE), and NDF digestibility in corn-based diets fed to growing pigs. Eighteen growing pigs (33.8 ± 2.2 kg BW) were surgically fitted with a T-cannula in the distal ileum and allocated to 1 of 6 dietary treatment groups in a 3-period incomplete Latin square design, with 9 observations per treatment. Six dietary treatments were obtained by adding 0, 20, and 40% DDGS to corn-casein diets formulated with 2 and 6% SBO. Ileal digesta and fecal samples were collected and the apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD) of AEE and NDF and the AID of AA were determined. Apparent values were corrected for endogenous losses of lipids, and true ileal (TID) and true total tract digestibility (TTTD) values of lipids were calculated. Results showed that the AID of Lys decreased ( < 0.001) with the inclusion of DDGS but was not affected ( = 0.63) by the inclusion of SBO. An interaction between DDGS and SBO on the AID ( = 0.002) and ATTD ( = 0.009) of NDF was observed, where the AID and ATTD of NDF decreased with DDGS at 6% SBO but no effect was observed at 2% SBO. The AID of NDF increased with SBO at 0% DDGS, but no effect was observed at 20 or 40% DDGS. An interaction between DDGS and SBO on the AID ( = 0.011) and ATTD ( = 0.008) of AEE was observed, where the AID and ATTD of AEE increased with SBO. The AID and ATTD of AEE increased with DDGS at 2% SBO, but no effect was observed at 6% SBO. Correction by ileal and fecal endogenous loss of AEE (9.5 and 13.6 g/kg of DMI, respectively) showed that increasing dietary AEE had no effect on the TID and TTD of AEE ( > 0.05). In conclusion, the AID of Lys decreased with DDGS and was not affected by lipids from SBO. The greatest AID and ATTD of NDF was observed in diets with a high AEE and low NDF content. Low values of apparent digestibility of AEE in lower-lipid diets are possibly the result of endogenous losses of lipids, because the true digestibility of AEE was not affected by the dietary increase of AEE.

Coinfections involving porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) contribute to a group of disease syndromes known as porcine circovirus-associated disease (PCVAD). Presumably, PRRSV infection enhances PCV2 replication as a result of modulation of host immunity. The purpose of this study was to evaluate PCV2 replication and pathogenesis in pigs vaccinated with a PRRS modified live virus (MLV) vaccine and subsequently challenged with a combination of PRRSV and PCV2. During the early postchallenge period, the number of pigs with PRRSV-associated clinical signs was decreased, and average daily gain (ADG) was increased, in the vaccinated group, demonstrating the protective effect of PRRS vaccination. However, during the later postchallenge period, more pigs in the vaccinated group showed increased PCV2 viremia, decreased ADG, increased PCVAD clinical signs, and increased mortality. In this disease model, the early benefits of PRRSV vaccination were outweighed by the later amplification of PCVAD., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Studies have shown that intramuscular adipogenesis and fibrogenesis may concomitantly occur in skeletal muscle of beef cattle. Thus, we hypothesized that the discrepancy of intramuscular fat content in beef from Nellore and Angus was associated with differences in intramuscular adipogenesis and fibrogenesis during the finishing phase. To test our hypothesis, longissimus muscle samples of Nellore (n = 6; BW = 372.5 ± 37.3 kg) and Angus (n = 6; BW = 382.8 ± 23.9 kg) cattle were collected for analysis of gene and protein expression, and quantification of intramuscular fat and collagen. Least-squares means were estimated for the effect of Breed and differences were considered at P ≤ 0.05. A greater intramuscular fat content was observed in skeletal muscle of Angus compared to Nellore cattle (P≤0.05). No differences were observed for mRNA expression of lipogenic and lipolytic markers ACC, FAS, FABP4, SERBP-1, CPT-2, LPL, and ACOX (P > 0.05) in skeletal muscle of Nellore and Angus cattle. Similarly, no differences were observed in mRNA expression of adipogenic markers Zfp423, PPARγ, and C/EBPα (P>0.05) However, a greater PPARγ protein content was observed in skeletal muscle of Angus compared to Nellore cattle (P≤0.05). A greater abundance of adipo/fibrogenic cells, evaluated by the PDGFRα content, was observed in skeletal muscle of Angus than Nellore cattle (P≤0.05). No differences in fibrogenesis were observed in skeletal muscle of Angus and Nellore cattle, which is in accordance with the lack of differences in intramuscular collagen content in beef from both breeds (P>0.05). These findings demonstrate that difference in intramuscular fat content is associated with a slightly enhanced adipogenesis in skeletal muscle of Angus compared to Nellore cattle, while no difference in fibrogenesis.

Mutations in >30 genes are known to result in impairment of the adaptive immune system, causing a group of disorders collectively known as SCID. SCID disorders are split into groups based on their presence and/or functionality of B, T, and NK cells. Piglets from a line of Yorkshire pigs at Iowa State University were shown to be affected by T(-)B(-)NK(+) SCID, representing, to our knowledge, the first example of naturally occurring SCID in pigs. In this study, we present evidence for two spontaneous mutations as the molecular basis for this SCID phenotype. Flow cytometry analysis of thymocytes showed an increased frequency of immature T cells in SCID pigs. Fibroblasts from these pigs were more sensitive to ionizing radiation than non-SCID piglets, eliminating the RAG1 and RAG2 genes. Genetic and molecular analyses showed that two mutations were present in the Artemis gene, which in the homozygous or compound heterozygous state cause the immunodeficient phenotype. Rescue of SCID fibroblast radiosensitivity by human Artemis protein demonstrated that the identified Artemis mutations are the direct cause of this cellular phenotype. The work presented in the present study reveals two mutations in the Artemis gene that cause T(-)B(-)NK(+) SCID in pigs. The SCID pig can be an important biomedical model, but these mutations would be undesirable in commercial pig populations. The identified mutations and associated genetic tests can be used to address both of these issues., (Copyright © 2015 by The American Association of Immunologists, Inc.)

Background: Previously, we identified a major quantitative trait locus (QTL) for host response to Porcine Respiratory and Reproductive Syndrome virus (PRRSV) infection in high linkage disequilibrium (LD) with SNP rs80800372 on Sus scrofa chromosome 4 (SSC4)., Results: Within this QTL, guanylate binding protein 5 (GBP5) was differentially expressed (DE) (p < 0.05) in blood from AA versus AB rs80800372 genotyped pigs at 7,11, and 14 days post PRRSV infection. All variants within the GBP5 transcript in LD with rs80800372 exhibited allele specific expression (ASE) in AB individuals (p < 0.0001). A transcript re-assembly revealed three alternatively spliced transcripts for GBP5. An intronic SNP in GBP5, rs340943904, introduces a splice acceptor site that inserts five nucleotides into the transcript. Individuals homozygous for the unfavorable AA genotype predominantly produced this transcript, with a shifted reading frame and early stop codon that truncates the 88 C-terminal amino acids of the protein. RNA-seq analysis confirmed this SNP was associated with differential splicing by QTL genotype (p < 0.0001) and this was validated by quantitative capillary electrophoresis (p < 0.0001). The wild-type transcript was expressed at a higher level in AB versus AA individuals, whereas the five-nucleotide insertion transcript was the dominant form in AA individuals. Splicing and ASE results are consistent with the observed dominant nature of the favorable QTL allele. The rs340943904 SNP was also 100 % concordant with rs80800372 in a validation population that possessed an alternate form of the favorable B QTL haplotype., Conclusions: GBP5 is known to play a role in inflammasome assembly during immune response. However, the role of GBP5 host genetic variation in viral immunity is novel. These findings demonstrate that rs340943904 is a strong candidate causal mutation for the SSC4 QTL that controls variation in host response to PRRSV.

An experiment was conducted to determine the quantitative relationships between standardized total tract digestible P (STTD P) and total Ca intakes with their retention and excretion by growing pigs fed corn-soybean meal diets. Forty-eight crossbred barrows (BW = 22.7 ± 2.9 kg) were allotted to 1 of 8 diets, housed individually in pens for 3 wk, and then moved to metabolism crates and allowed 4 d for adaptation and 5 d for collection of urine and fecal samples. Eight corn-soybean meal diets were formulated for similar NE, fat, and AA concentrations but to increase the STTD P from 0.16 to 0.62% using monocalcium phosphate. Dietary treatments were formulated for a constant Ca:STTD P ratio (2.2:1). The STTD P intake increased (P < 0.001) from 64 to 242% of the daily requirement (4.59 g/d of STTD P). Fecal and total excretion of P and Ca were linearly associated with mineral intake (P < 0.001). Constant urinary P excretion of 0.03 g/d P was observed, but at 4.96 g/d of STTD P intake, the urinary P excretion increased (P < 0.001). In contrast, Ca excretion in urine decreased (P < 0.001) with Ca intake, but constant excretion of 0.40 g/d Ca was reached at 17.97 g/d of Ca intake. The daily intakes of STTD P and Ca moderately explained the variation in urinary excretion of P (R2= 0.41) and Ca (R2= 0.64). The absorption and retention of P increased linearly (P< 0.001) with dietary P intake, whereas absorption and retention of Ca showed a quadratic response (P < 0.001). Absorption and retention of P and Ca were highly predictable from the STTD P and Ca intakes, with of 0.87 and 0.90, respectively. The femur mineral content (FMC) increased by 2.71 g with STTD P intake (P < 0.001) but reached a plateau (29.54 g of FMC) at 8.84 g/d of STTD P intake. The FMC was highly predictable from the STTD P intake (R2 = 0.89). The FMC affected the urinary P excretion ( P< 0.01), but moderately (R2= 0.19) explained the variation in urinary P. In conclusion, constant excretion of P in urine was observed but excretion increased linearly at STTD P intake levels above the requirement for maximum growth of growing pigs. The FMC increased with STTD P intake, but a plateau was reached at a STTD P intake level above the requirement. Dietary STTD P was used for growth and accumulated in bones until a plateau was reached and excess was excreted in urine. The predictability of P and Ca excretion in urine from the dietary STTD P and Ca intakes was moderate.

An experiment was conducted to determine a best fitting dietary fiber (DF) component to estimate the effect of DF concentration on the digestibility of energy, DF, and AA and energy value of 9 corn coproducts: corn bran (37.0% total nonstarch polysaccharides [NSP]); corn bran with solubles (17.1% NSP); cooked corn distillers dried grains with solubles (DDGS; 20.4% NSP); reduced oil DDGS (25.0% NSP); uncooked DDGS (22.0% NSP); high protein distillers dried grains (21.9% NSP); dehulled, degermed corn (1.1% NSP); corn germ meal (44.4% NSP); and corn gluten meal (4.9% NSP). A total of 20 growing pigs (initial BW: 25.9 ± 2.5 kg) were fitted with a T-cannula in the distal ileum and allotted to 10 dietary treatment groups in a 4-period incomplete block design with 8 observations per treatment. Treatments included a corn-soybean meal-based basal diet and 9 diets obtained by mixing 70% of the basal diet with 30% of the test ingredient. In tested ingredients, 11 DF components were determined: 1) ADF, 2) NDF, 3) total dietary fiber, 4) hemicellulose, 5) total NSP, 6) NSP arabinose, 7) NSP xylose, 8) NSP mannose, 9) NSP glucose, 10) NSP galactose, and 11) arabinoxylan. The apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD) of GE, DM, and NDF and the AID of AA of ingredients were measured. A single best fitting DF component was assessed and ranked for each trait, showing that arabinoxylan concentration best explained variance in AID of GE (R(2) = 0.65; cubic, P < 0.01) and DM (R(2) = 0.67; cubic, P < 0.01). The NSP xylose residue best explained variance in ATTD of GE (R(2) = 0.80; cubic, P < 0.01), DM (R(2) = 0.78; cubic, P < 0.01), and NDF (R(2) = 0.63; cubic, P < 0.01); AID of Met (R(2) = 0.40; cubic, P = 0.02), Met + Cys (R(2) = 0.44; cubic, P = 0.04), and Trp (R(2) = 0.11; cubic, P = 0.04); and DE (R(2) = 0.66; linear, P = 0.02) and ME (R(2) = 0.71; cubic, P = 0.01) values. The AID of Lys was not predictable (P > 0.05) from the DF concentration. In conclusion, the arabinoxylan and NSP xylose residue were the DF components that best explained variation due to DF concentration and, with the exception of AID of Lys, can be used to predict the digestibility of energy and DF and the DE and ME values in corn coproducts.

Twenty-four pregnant Nellore cows were randomly assigned into 2 feeding level groups (control [CTL]; fed 1.0 times the maintenance requirement; n = 12; and overnourished [ON]; fed at 1.5 times the maintenance requirement; n = 12) to evaluate effects of maternal overnutrition on fetal skeletal muscle development. Cows were slaughtered at 135, 190, and 240 d of gestation and samples of fetal LM were collected for analysis of mRNA expression analysis and for histological evaluation of collagen content and number of muscle cells. There was no interaction between gestational period and maternal nutrition for the variables evaluated (P > 0.05). The mRNA expression of Cadherin-associated protein, β 1 (β-catenin) tended to be greater in fetuses from ON cows (P = 0.08), while myogenic differentiation 1 (MyoD; P = 0.56), myogenin (MyoG; P = 0.70), and the number of muscle cells (P = 0.90) were not affected by maternal overnutrition. Gestational period did not affect the mRNA expression of β-catenin (P = 0.60) and MyoG (P = 0.21). The mRNA expression of MyoD tended to increase with days of gestation (P = 0.06). The mRNA expression of zinc finger protein 423 (Zfp423; P < 0.0001), C/EBPα (P = 0.01), and PPARγ (P < 0.0001) were enhanced in ON fetuses. No effects of days of gestation were observed for mRNA expression of Zfp423 (P = 0.75) and C/EBPα (P = 0.48). The mRNA expression of PPARγ in fetuses at 190 d of gestation tended to be greater than those at 135 and 240 d of gestation (P = 0.06). The mRNA expression of transforming growth factor β (TGF-β; P < 0.0001), collagen type III, α I (COL3A1; P < 0.0001), and collagen content (P = 0.01) were increased in ON fetuses. Gestational period did not affect the mRNA expression of collagen type I, α I (COL1A1; P = 0.65). The mRNA expression of COL3A1 (P = 0.09) in fetuses at 190 d of gestation tended to be greater than fetuses at 135 and 240 d of gestation. The mRNA expression of TGF-β in fetuses at 190 d of gestation was greater than in fetuses at 135 d of gestation (P = 0.03), and the values observed in fetuses at 240 d of gestation did not differ from the other gestational time points. The least value of collagen content (P = 0.01) was observed in fetuses at 135 d of gestation, and no differences were observed among the other gestational time points. These data shows that maternal overnutrition enhances fibrogenesis and likely adipogenesis without compromising myogenesis in fetal skeletal muscle of cattle.

Porcine reproductive and respiratory syndrome (PRRS) is the most economically significant disease impacting pig production in North America, Europe, and Asia, causing reproductive losses such as increased rates of stillbirth and mummified piglets. The objective of this study was to explore the genetic basis of host response to the PRRS virus (PRRSV) in a commercial multiplier sow herd before and after a PRRS outbreak, using antibody response and reproductive traits. Reproductive data comprising number born alive (NBA), number alive at 24 h (NA24), number stillborn (NSB), number born mummified (NBM), proportion born dead (PBD), number born dead (NBD), number weaned (NW), and number of mortalities through weaning (MW) of 5,227 litters from 1,967 purebred Landrace sows were used along with a pedigree comprising 2,995 pigs. The PRRS outbreak date was estimated from rolling averages of farrowing traits and was used to split the data into a pre-PRRS phase and a PRRS phase. All 641 sows in the herd during the outbreak were blood sampled 46 d after the estimated outbreak date and were tested for anti-PRRSV IgG using ELISA (sample-to-positive [S/P] ratio). Genetic parameters of traits were estimated separately for the pre-PRRS and PRRS phase data sets. Sows were genotyped using the PorcineSNP60 BeadChip, and genome-wide association studies (GWAS) were performed using method Bayes B. Heritability estimates for reproductive traits ranged from 0.01 (NBM) to 0.12 (NSB) and from 0.01 (MW) to 0.12 (NBD) for the pre-PRRS and PRRS phases, respectively. S/P ratio had heritability (0.45) and strong genetic correlations with most traits, ranging from -0.72 (NBM) to 0.73 (NBA). In the pre-PRRS phase, regions associated with NSB and PBD explained 1.6% and 3% of the genetic variance, respectively. In the PRRS phase, regions associated with NBD, NSB, and S/P ratio explained 0.8%, 11%, and 50.6% of the genetic variance, respectively. For S/P ratio, 2 regions on SSC 7 (SSC7) separated by 100 Mb explained 40% of the genetic variation, including a region encompassing the major histocompatibility complex, which explained 25% of the genetic variance. These results indicate a significant genomic component associated with PRRSV antibody response and NSB in this data set. Also, the high heritability and genetic correlation estimates for S/P ratio during the PRRS phase suggest that S/P ratio could be used as an indicator of the impact of PRRS on reproductive traits.

Single nucleotide polymorphisms (SNPs) associated with average daily gain (ADG) and dry matter intake (DMI), two major components of feed efficiency in cattle, were identified in a genome-wide association study (GWAS). Uni- and multi-SNP models were used to describe feed efficiency in a training data set and the results were confirmed in a validation data set. Results from the univariate and bivariate analyses of ADG and DMI, adjusted by the feedlot beef steer maintenance requirements, were compared. The bivariate uni-SNP analysis identified (P-value <0.0001) 11 SNPs, meanwhile the univariate analyses of ADG and DMI identified 8 and 9 SNPs, respectively. Among the six SNPs confirmed in the validation data set, five SNPs were mapped to KDELC2, PHOX2A, and TMEM40. Findings from the uni-SNP models were used to develop highly accurate predictive multi-SNP models in the training data set. Despite the substantially smaller size of the validation data set, the training multi-SNP models had slightly lower predictive ability when applied to the validation data set. Six Gene Ontology molecular functions related to ion transport activity were enriched (P-value <0.001) among the genes associated with the detected SNPs. The findings from this study demonstrate the complementary value of the uni- and multi-SNP models, and univariate and bivariate GWAS analyses. The identified SNPs can be used for genome-enabled improvement of feed efficiency in feedlot beef cattle, and can aid in the design of empirical studies to further confirm the associations.

Background: General, breed- and diet-dependent associations between feed efficiency in beef cattle and single nucleotide polymorphisms (SNPs) or haplotypes were identified on a population of 1321 steers using a 50 K SNP panel. Genomic associations with traditional two-step indicators of feed efficiency - residual feed intake (RFI), residual average daily gain (RADG), and residual intake gain (RIG) - were compared to associations with two complementary one-step indicators of feed efficiency: efficiency of intake (EI) and efficiency of gain (EG). Associations uncovered in a training data set were evaluated on independent validation data set. A multi-SNP model was developed to predict feed efficiency. Functional analysis of genes harboring SNPs significantly associated with feed efficiency and network visualization aided in the interpretation of the results., Results: For the five feed efficiency indicators, the numbers of general, breed-dependent, and diet-dependent associations with SNPs (P-value < 0.0001) were 31, 40, and 25, and with haplotypes were six, ten, and nine, respectively. Of these, 20 SNP and six haplotype associations overlapped between RFI and EI, and five SNP and one haplotype associations overlapped between RADG and EG. This result confirms the complementary value of the one and two-step indicators. The multi-SNP models included 89 SNPs and offered a precise prediction of the five feed efficiency indicators. The associations of 17 SNPs and 7 haplotypes with feed efficiency were confirmed on the validation data set. Nine clusters of Gene Ontology and KEGG pathway categories (mean P-value < 0.001) including, 9nucleotide binding; ion transport, phosphorous metabolic process, and the MAPK signaling pathway were overrepresented among the genes harboring the SNPs associated with feed efficiency., Conclusions: The general SNP associations suggest that a single panel of genomic variants can be used regardless of breed and diet. The breed- and diet-dependent associations between SNPs and feed efficiency suggest that further refinement of variant panels require the consideration of the breed and management practices. The unique genomic variants associated with the one- and two-step indicators suggest that both types of indicators offer complementary description of feed efficiency that can be exploited for genome-enabled selection purposes.

Intramuscular fat and collagen content are major factors affecting beef quality, but mechanisms regulating intramuscular adipose and connective tissue deposition are far from clear. Japanese Wagyu cattle are well known for their extremely high marbling. The objective of this study was to evaluate intramuscular fat (IMF) and collagen deposition in the muscle of Wagyu compared with Angus cattle. Animals were managed under the same condition and slaughtered at an averaging 585 ± 12.1 kg of BW. Samples of sternomandibularis muscle were collected from Wagyu (n = 3) and Angus (n = 3) for molecular and histological investigations of adipogenesis and fibrogenesis. With exception of C/EBPβ (P = 0.2864), the expression of the adipogenic markers C/EBPα (P = 0.008), PPARγ (P = 0.028), and zip finger protein 423 (Zfp423; P = 0.047) in Wagyu were greater than in Angus muscle, which was consistent with greater IMF deposition in Wagyu (P < 0.05). In addition, more adipocytes and preadipocytes were detected intramuscularly in Wagyu cattle. Similarly, fibrogenesis was also enhanced in Wagyu, with a greater expression of fibroblast growth factor (FGF)-2 (P = 0.028), FGF receptor 1 (P = 0.030), transforming growth factor (TGF)-β (P = 0.028), collagen I (P = 0.012), and collagen III (P = 0.025). Similarly, Wagyu muscle had greater collagen content (P = 0.002) and decreased collagen solubility (P = 0.005). In addition, muscle fiber diameter was larger (P < 0.0001) in Wagyu than in Angus cattle. These results clearly show that both IMF and collagen contents are enhanced in Wagyu cattle and more adipogenic cells are detected in Wagyu muscle, indicating intramuscular adipogenesis is enhanced in Wagyu compared with Angus muscle.

Carcass and meat quality traits of 16 pregnant and 5 non-pregnant cows fed at 1.2 times maintenance and 16 pregnant and 6 non-pregnant fed ad libitum were evaluated. Pregnancy did not affect final body weight (FBW; P=0.0923), cold carcass yield (CCY; P=0.0513), longissimus muscle area (LMA; P=0.8260), rib fat thickness (RFT; P=0.1873) and shear force (WBSF; P=0.9707). A lower FBW (P=0.0028), LMA (P=0.0048) and RFT (P=0.0001) were observed in feed restricted cows. However, no differences were found for CCY (P=0.7243) and WBSF (P=0.0759) among feeding level groups. These data suggests that carcass and meat quality traits are not affected by pregnancy status in Nellore cows. Moreover, although cows experiencing feed restriction did have reduced deposition of subcutaneous fat and lean tissue, there were no major impacts on meat quality traits., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Alternative exon usage (AEU) is an important component of gene regulation. Exon expression platforms allow the detection of associations between AEU and phenotypes such as cancer. Numerous studies have identified associations between gene expression and the brain cancer glioblastoma multiforme (GBM). The few consistent gene expression biomarkers of GBM that have been reported may be due to the limited consideration of AEU and the analytical approaches used. The objectives of this study were to develop a model that accounts for the variations in expression present between the exons within a gene and to identify AEU biomarkers of GBM survival., Methods: The expression of exons corresponding to 25,403 genes was related to the survival of 250 individuals diagnosed with GBM in a training data set. Genes exhibiting AEU in the training data set were confirmed in an independent validation data set of 78 patients. A hierarchical mixed model that allows the consideration of covariation between exons within a gene and of the effect of the epidemiological characteristics of the patients was developed to identify associations between exon expression and patient survival. This general model describes all three possible scenarios: multi-exon genes with and without AEU, and single-exon genes., Results: AEU associated with GBM survival was identified on 2477 genes (P-value < 5.0E-04 or FDR-adjusted P-value < 0.05). G-protein coupled receptor 98 (Gpr98) and epidermal growth factor (Egf) were among the genes exhibiting AEU with 30 and 9 exons associated with GBM survival, respectively. Pathways enriched among the AEU genes included focal adhesion, ECM-receptor interaction, ABC transporters and pathways in cancer. In addition, 24 multi-exon genes without AEU and 8 single-exon genes were associated with GBM survival (FDR-adjusted P-value < 0.05)., Conclusions: The inferred patterns of AEU were consistent with in silico AS models. The hierarchical model used offered a flexible and simple way to interpret and identify associations between survival that accommodates multi-exon genes with or without AEU and single exon genes. Our results indicate that differential expression of AEU could be used as biomarker for GBM and potentially other cancers.

Aim: To identify and study targets of microRNA biomarkers of glioblastoma survival across events (death and recurrence) and phases (life expectancy or post-diagnostic) using functional and network analyses., Materials and Methods: microRNAs associated with glioblastoma survival within and across race, gender, recurrence, and therapy cohorts were identified using 253 individuals, 534 microRNAs, Cox survival model, cross-validation, discriminant analyses, and cross-study comparison., Results: All 45 microRNAs revealed as being associated with survival were confirmed in independent cancer studies and 25 in glioblastoma studies. Thirty-nine and six microRNAs (including hsa-miR-222) were associated with one and multiple glioblastoma survival indicators, respectively. Nineteen and 26 microRNAs exhibited cohort-dependent (including hsa-miR-10b with therapy and hsa-miR-486 with race) and independent associations with glioblastoma, respectively., Conclusion: Sensory perception and G protein-coupled receptor processes were enriched among microRNA gene targets also associated with survival and network visualization highlighted their relations. These findings can help to improve prognostic tools and personalized treatments.

Carcasses of sixty-three Nellore bulls slaughtered at a commercial beef plant were randomly selected by dental classification (2, 4, 6 or 8 permanent incisors) in order to evaluate the influence of dental maturity on carcass traits and meat quality. Carcasses with 8 permanent incisors (p.i.) had greatest values (P<0.05) of carcass weight and longissimus area. Carcasses with 4 and 6 p.i. presented similar values of rib fat thickness being greater (P<0.05) than the other groups. Carcasses with 6 and 8 p.i. presented greater (P<0.05) values of shear force than the other groups. Conversely, carcasses with 2 and 4 p.i. displayed greater (P<0.05) myofibrillar fragmentation index and collagen solubility. Greatest values of thawing loss were observed in carcasses with 2 p.i. (P<0.05) while carcasses with 8 p.i. presented greatest values (P<0.05) of drip loss. Regarding longissimus color, carcasses with 8 p.i presented greatest value (P<0.05) of b*. Data suggests that dental maturity influences carcass traits and meat quality of Nellore bulls., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Glioblastoma is a complex multifactorial disorder that has swift and devastating consequences. Few genes have been consistently identified as prognostic biomarkers of glioblastoma survival. The goal of this study was to identify general and clinical-dependent biomarker genes and biological processes of three complementary events: lifetime, overall and progression-free glioblastoma survival., Methods: A novel analytical strategy was developed to identify general associations between the biomarkers and glioblastoma, and associations that depend on cohort groups, such as race, gender, and therapy. Gene network inference, cross-validation and functional analyses further supported the identified biomarkers., Results: A total of 61, 47 and 60 gene expression profiles were significantly associated with lifetime, overall, and progression-free survival, respectively. The vast majority of these genes have been previously reported to be associated with glioblastoma (35, 24, and 35 genes, respectively) or with other cancers (10, 19, and 15 genes, respectively) and the rest (16, 4, and 10 genes, respectively) are novel associations. Pik3r1, E2f3, Akr1c3, Csf1, Jag2, Plcg1, Rpl37a, Sod2, Topors, Hras, Mdm2, Camk2g, Fstl1, Il13ra1, Mtap and Tp53 were associated with multiple survival events.Most genes (from 90 to 96%) were associated with survival in a general or cohort-independent manner and thus the same trend is observed across all clinical levels studied. The most extreme associations between profiles and survival were observed for Syne1, Pdcd4, Ighg1, Tgfa, Pla2g7, and Paics. Several genes were found to have a cohort-dependent association with survival and these associations are the basis for individualized prognostic and gene-based therapies. C2, Egfr, Prkcb, Igf2bp3, and Gdf10 had gender-dependent associations; Sox10, Rps20, Rab31, and Vav3 had race-dependent associations; Chi3l1, Prkcb, Polr2d, and Apool had therapy-dependent associations. Biological processes associated glioblastoma survival included morphogenesis, cell cycle, aging, response to stimuli, and programmed cell death., Conclusions: Known biomarkers of glioblastoma survival were confirmed, and new general and clinical-dependent gene profiles were uncovered. The comparison of biomarkers across glioblastoma phases and functional analyses offered insights into the role of genes. These findings support the development of more accurate and personalized prognostic tools and gene-based therapies that improve the survival and quality of life of individuals afflicted by glioblastoma multiforme.

The effects of two levels of concentrate and ruminally undegradable protein (RUP) on performance, intake, digestibility, carcass characteristics, meat quality traits, and commercial cuts yield were assessed. Twenty crossbred heifers (240 kg average body weight) were used. At the beginning of the trial, four animals were slaughtered as reference group and the 16 remaining animals were randomly assigned to four treatments, in a 2 × 2 factorial design: two levels of concentrate (40% and 80%, dry matter (DM) basis) and two levels of RUP (48.79% and 27.19% of CP). At the end of the trial, all the animals were slaughtered. There was no interaction (P > 0.05) between concentrate and RUP levels. Dry matter intake and nutrients digestibility was not affected (P > 0.05) by RUP level. Heifers fed the highest RUP level had greater (P < 0.05) average daily gain (ADG). Concentrate level did not affect (P > 0.05) DMI and ADG. Heifers fed diets with 80% concentrate had greater intake of TDN and EE, and lower intake of NDF (P < 0.05). The digestibilities of all nutrients, except the NDF, were greater (P < 0.05) for the 80% concentrate diets. The RUP levels did not affect (P > 0.05) the carcass characteristics and carcass gain composition. Heifers fed 80% concentrate diets had larger (P < 0.05) longissimus muscle area and lower gain of bones (P < 0.05). Concentrate level did not affect (P > 0.05) the composition of carcass gain. There was no effect (P > 0.05) of RUP and concentrate levels on meat quality traits and commercial cut yields.

Seventy-two pigs of three genetic groups (Brazilian indigenous breed Piau, Commercial line and Crossbred) of both sexes were slaughtered at four live weights (30, 60, 90 and 120 kg). Intramuscular fat (IMF) content in Longissimus dorsi muscle of each animal was extracted and correlated with candidate gene mRNA expression (ATN1, EEF1A2, FABP3, LDLR, MGP, OBSCN, PDHB, TRDN and RYR1). Within slaughter weight of 120 kg, Piau and Crossbred pigs showed higher IMF content (p < 0.05) than commercial animals, with 2.48, 2.08 and 1.00% respectively. Barrows presented higher values of IMF (p < 0.05) than gilts (1.54 and 1.30% respectively). Gene expression of EEF1A2, FABP3, LDLR, OBSCN, PDHB, TRDN and RYR1 were correlated with IMF (p < 0.05) using the whole dataset. For Piau data only, expression of FABP3, LDLR, MGP, OBSCN, PDHB, TRDN and RYR1 showed correlation with IMF (p < 0.05). Genes that have important roles in lipid transportation inside the cell (FABP3) and tissues (LDLR) showed correlation with IMF of, respectively, 0.68 and 0.63 using the whole data set, and 0.90 and 0.91 using data from Piau animals. The highly positive correlation of the LDLR and FAPB3 expression with IMF content may confirm that these genes are important for fat deposition in the porcine L. dorsi muscle., (© 2010 Blackwell Verlag GmbH.)