Analyses of plasma metabolites using a high performance four-channel CIL LC-MS method and identification of metabolites associated with enteric methane emissions in beef cattle.

Reducing enteric methane (one greenhouse gas) emissions from beef cattle not only can be beneficial in reducing global warming, but also improve efficiency of nutrient utilization in the production system. However, direct measurement of enteric methane emissions on individual cattle is difficult and expensive. The objective of this study was to detect plasma metabolites that are associated with enteric methane emissions in beef cattle. Average enteric methane emissions (CH4) per day (AVG_DAILYCH4) for each individual cattle were measured using the GreenFeed emission monitoring (GEM) unit system, and beef cattle with divergent AVG_DAILYCH4 from Angus (n = 10 for the low CH4 group and 9 for the high CH4 group), Charolais (n = 10 for low and 10 for = high), and Kinsella Composite (n = 10 for low and 10 for high) populations were used for plasma metabolite quantification and metabolite-CH4 association analyses. Blood samples of these cattle were collected near the end of the GEM system tests and a high performance four-channel chemical isotope labeling (CIL) liquid chromatography (LC) mass spectrometer (MS) method was applied to identify and quantify concentrations of metabolites. The four-channel CIL LC-MS method detected 4235 metabolites, of which 1105 were found to be significantly associated with AVG_DAILYCH4 by a t-test, while 1305 were significantly associated with AVG_DAILYCH4 by a regression analysis at p<0.05. Both the results of the t-test and regression analysis revealed that metabolites that were associated with enteric methane emissions in beef cattle were largely breed-specific whereas 4.29% to 6.39% CH4 associated metabolites were common across the three breed populations and 11.07% to 19.08% were common between two breed populations. Pathway analyses of the CH4 associated metabolites identified top enriched molecular processes for each breed population, including arginine and proline metabolism, arginine biosynthesis, butanoate metabolism, and glutathione metabolism for Angus; beta-alanine metabolism, pyruvate metabolism, glycolysis / gluconeogenesis, and citrate cycle (TCA cycle) for Charolais; phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, arginine biosynthesis, and arginine and proline metabolism for Kinsella Composite. The detected CH4 associated metabolites and enriched molecular processes will help understand biological mechanisms of enteric methane emissions in beef cattle. The detected CH4 associated plasma metabolites will also provide valuable resources to further characterize the metabolites and verify their utility as biomarkers for selection of cattle with reduced methane emissions.

Sequence-based GWAS meta-analyses for beef production traits.

BACKGROUND: Combining the results of within-population genome-wide association studies (GWAS) based on whole-genome sequences into a single meta-analysis (MA) is an accurate and powerful method for identifying variants associated with complex traits. As part of the H2020 BovReg project, we performed sequence-level MA for beef production traits. Five partners from France, Switzerland, Germany, and Canada contributed summary statistics from sequence-based GWAS conducted with 54,782 animals from 15 purebred or crossbred populations. We combined the summary statistics for four growth, nine morphology, and 15 carcass traits into 16 MA, using both fixed effects and z-score methods. RESULTS: The fixed-effects method was generally more informative to provide indication on potentially causal variants, although we combined substantially different traits in each MA. In comparison with within-population GWAS, this approach highlighted (i) a larger number of quantitative trait loci (QTL), (ii) QTL more frequently located in genomic regions known for their effects on growth and meat/carcass traits, (iii) a smaller number of genomic variants within the QTL, and (iv) candidate variants that were more frequently located in genes. MA pinpointed variants in genes, including MSTN, LCORL, and PLAG1 that have been previously associated with morphology and carcass traits. We also identified dozens of other variants located in genes associated with growth and carcass traits, or with a function that may be related to meat production (e.g., HS6ST1, HERC2, WDR75, COL3A1, SLIT2, MED28, and ANKAR). Some of these variants overlapped with expression or splicing QTL reported in the cattle Genotype-Tissue Expression atlas (CattleGTEx) and could therefore regulate gene expression. CONCLUSIONS: By identifying candidate genes and potential causal variants associated with beef production traits in cattle, MA demonstrates great potential for investigating the biological mechanisms underlying these traits. As a complement to within-population GWAS, this approach can provide deeper insights into the genetic architecture of complex traits in beef cattle.

Genome-wide association study for primal cut lean traits in Canadian beef cattle.

This study identified genomic variants and underlying candidate genes related to the whole carcass and individual primal cut lean content in Canadian commercial crossbred beef cattle. Genotyping information of 1035 crossbred beef cattle were available alongside estimated and actual carcass lean meat yield and individual primal cut lean content in all carcasses. Significant fixed effects and covariates were identified and included in the animal model. Genome-wide association analysis were implemented using the weighted single-step genomic best linear unbiased prediction (WssGBLUP). A number of candidate genes identified linked to lean tissue production were unrelated to estimated lean meat yield and were specific to the actual lean traits. Among these, 41 genes were common for actual lean traits, on specific regions of BTA4, BTA13 and BTA25 indicating potential involvement in lean mass synthesis. Therefore, the results suggested the inclusion of primal cut lean traits as a selection objective in breeding programs with consideration of further functional studies of the identified genes could help in optimizing lean yield for maximal carcass value.

Estimation of genetic parameters for primal tissue component traits in commercial crossbred beef cattle.

Knowledge of genetic parameters is required to select for optimal yield of primal cuts that may be used as the selection criteria for designing future breeding programs. This study aimed to estimate the heritability, as well as genetic and phenotypic correlations of primal cut lean and fat tissue components, and carcass traits in Canadian crossbred beef cattle. All tissue component traits presented a medium to high heritability (lean 0.41 to 0.61; fat 0.46 to 0.62; bone 0.22 to 0.48), which indicates a probable increase in their response to genetic selection. In addition, high genetic correlations were found among the primal cut lean trait group (0.63 to 0.94) and fat trait group (0.63 to 0.94), as well as strong negative correlations between lean and fat component traits (-0.63 to -1). Therefore, results suggested inclusion of primal cut tissue composition traits as a selection objective in breeding programs with consideration of correlations among the traits could help in optimizing lean yield for the highest carcass value.

Genome-Wide Association Study of Nucleotide Variants Associated with Resistance to Nine Antimicrobials in Mycoplasma bovis.

Antimicrobial resistance (AMR) studies of Mycoplasma bovis have generally focused on specific loci versus using a genome-wide association study (GWAS) approach. A GWAS approach, using two different models, was applied to 194 Mycoplasma bovis genomes. Both a fixed effects linear model (FEM) and a linear mixed model (LMM) identified associations between nucleotide variants (NVs) and antimicrobial susceptibility testing (AST) phenotypes. The AMR phenotypes represented fluoroquinolones, tetracyclines, phenicols, and macrolides. Both models identified known and novel NVs associated (Bonferroni adjusted p < 0.05) with AMR. Fluoroquinolone resistance was associated with multiple NVs, including previously identified mutations in gyrA and parC. NVs in the 30S ribosomal protein 16S were associated with tetracycline resistance, whereas NVs in 5S rRNA, 23S rRNA, and 50S ribosomal proteins were associated with phenicol and macrolide resistance. For all antimicrobial classes, resistance was associated with NVs in genes coding for ABC transporters and other membrane proteins, tRNA-ligases, peptidases, and transposases, suggesting a NV-based multifactorial model of AMR in M. bovis. This study was the largest collection of North American M. bovis isolates used with a GWAS for the sole purpose of identifying novel and non-antimicrobial-target NVs associated with AMR.

Breed dependent regulatory mechanisms of beneficial and non-beneficial fatty acid profiles in subcutaneous adipose tissue in cattle with divergent feed efficiency.

The current study aimed to determine whether breed and feed efficiency affect the molecular mechanisms regulating beneficial and non-beneficial fatty acid profiles in subcutaneous adipose tissue of beef steers. Fatty acid profiling and RNA-Seq based transcriptome analysis were performed on subcutaneous adipose tissues collected from beef steers with three divergent breeds (Angus, ANG, n = 47; Charolais, CHAR, n = 48; Kinsella Composite, KC, n = 48) and different residual feed intake (RFI, a measure of feed efficiency). The comparison of fatty acid profiles showed that KC had higher beneficial FAs compared to the other two breeds. Distinct FA profiles between H-RFIfat and L-RFIfat steers was more obvious for KC steers, where H-RFIfat steers tended to have higher proportion of healthy FAs and lower proportion of the unhealthy FAs. A higher number of differentially expressed (DE) genes were observed for KC steers, whereas ANG and CHAR steers had a lower number of DE genes between H- and L-RFIfat steers. The association analyses of the gene expressions and FA profiles showed that 10 FA metabolism-associated genes together with the one upstream regulator (SREBF1) were associated with the proportion of C18:2n-6, total n-6, PUFA and PUFA/SFA for KC steers but not the other two breeds. Subcutaneous adipose tissue FA profiles and healthy FA index differed in cattle with divergent feed efficiency and such variation was unique for the three examined cattle breeds. Key FA metabolism-associated genes together with SREBF1 which is the upstream regulator of a set of genes involved in lipid metabolism may be of importance for genetic selection of meat with higher healthy FA index in beef cattle.

Integrative analyses of genomic and metabolomic data reveal genetic mechanisms associated with carcass merit traits in beef cattle.

Improvement of carcass merit traits is a priority for the beef industry. Discovering DNA variants and genes associated with variation in these traits and understanding biological functions/processes underlying their associations are of paramount importance for more effective genetic improvement of carcass merit traits in beef cattle. This study integrates 10,488,742 imputed whole genome DNA variants, 31 plasma metabolites, and animal phenotypes to identify genes and biological functions/processes that are associated with carcass merit traits including hot carcass weight (HCW), rib eye area (REA), average backfat thickness (AFAT), lean meat yield (LMY), and carcass marbling score (CMAR) in a population of 493 crossbred beef cattle. Regression analyses were performed to identify plasma metabolites associated with the carcass merit traits, and the results showed that 4 (3-hydroxybutyric acid, acetic acid, citric acid, and choline), 6 (creatinine, L-glutamine, succinic acid, pyruvic acid, L-lactic acid, and 3-hydroxybutyric acid), 4 (fumaric acid, methanol, D-glucose, and glycerol), 2 (L-lactic acid and creatinine), and 5 (succinic acid, fumaric acid, lysine, glycine, and choline) plasma metabolites were significantly associated with HCW, REA, AFAT, LMY, and CMAR (P-value < 0.1), respectively. Combining the results of metabolome-genome wide association studies using the 10,488,742 imputed SNPs, 103, 160, 83, 43, and 109 candidate genes were identified as significantly associated with HCW, REA, AFAT, LMY, and CMAR (P-value < 1 × 10-5), respectively. By applying functional enrichment analyses for candidate genes of each trait, 26, 24, 26, 24, and 28 significant cellular and molecular functions were predicted for HCW, REA, AFAT, LMY, and CMAR, respectively. Among the five topmost significantly enriched biological functions for carcass merit traits, molecular transport and small molecule biochemistry were two top biological functions associated with all carcass merit traits. Lipid metabolism was the most significant biological function for LMY and CMAR and it was also the second and fourth highest biological function for REA and HCW, respectively. Candidate genes and enriched biological functions identified by the integrative analyses of metabolites with phenotypic traits and DNA variants could help interpret the results of previous genome-wide association studies for carcass merit traits. Our integrative study also revealed additional potential novel genes associated with these economically important traits. Therefore, our study improves understanding of the molecular and biological functions/processes that influence carcass merit traits, which could help develop strategies to enhance genomic prediction of carcass merit traits with incorporation of metabolomic data. Similarly, this information could guide management practices, such as nutritional interventions, with the purpose of boosting specific carcass merit traits.

Outcomes of epidural steroids following percutaneous transforaminal endoscopic discectomy: a meta-analysis and systematic review.

BACKGROUND: Percutaneous transforaminal endoscopic discectomy (PTED) has been widely used in the treatment of lumbar degenerative diseases. Epidural injection of steroids can reduce the incidence and duration of postoperative pain in a short period of time. Although steroids are widely believed to reduce the effect of surgical trauma, the observation indicators are not uniform, especially the long-term effects, so the problem remains controversial. Therefore, the purpose of this paper was to evaluate the efficacy of epidural steroids following PTED. METHODS: We searched PubMed, Embase, and the Cochrane Database from 1980 to June 2021 to identify randomized and non-randomized controlled trials comparing epidural steroids and saline alone following PTED. The primary outcomes included postoperative pain at least 6 months as assessed using a visual analogue scale (VAS) and the Oswestry Disability Index (ODI). The secondary outcomes included length of hospital stay and the time of return to work. RESULTS: A total of 451 patients were included in three randomized and two nonrandomized controlled trials. The primary outcomes, including VAS and ODI scores, did not differ significantly between epidural steroids following PTED and saline alone. There were no significant intergroup differences in length of hospital stay. Epidural steroids were shown to be superior in terms of the time to return to work (P < 0.001). CONCLUSIONS: Intraoperative epidural steroids did not provide significant benefits, leg pain control, improvement in ODI scores, and length of stay in the hospital, but it can enable the patient to return to work faster.

Identification of candidate genes and enriched biological functions for feed efficiency traits by integrating plasma metabolites and imputed whole genome sequence variants in beef cattle.

BACKGROUND: Feed efficiency is one of the key determinants of beef industry profitability and sustainability. However, the cellular and molecular background behind feed efficiency is largely unknown. This study combines imputed whole genome DNA variants and 31 plasma metabolites to dissect genes and biological functions/processes that are associated with residual feed intake (RFI) and its component traits including daily dry matter intake (DMI), average daily gain (ADG), and metabolic body weight (MWT) in beef cattle. RESULTS: Regression analyses between feed efficiency traits and plasma metabolites in a population of 493 crossbred beef cattle identified 5 (L-valine, lysine, L-tyrosine, L-isoleucine, and L-leucine), 4 (lysine, L-lactic acid, L-tyrosine, and choline), 1 (citric acid), and 4 (L-glutamine, glycine, citric acid, and dimethyl sulfone) plasma metabolites associated with RFI, DMI, ADG, and MWT (P-value < 0.1), respectively. Combining the results of metabolome-genome wide association studies using 10,488,742 imputed SNPs, 40, 66, 15, and 40 unique candidate genes were identified as associated with RFI, DMI, ADG, and MWT (P-value < 1 × 10-5), respectively. These candidate genes were found to be involved in some key metabolic processes including metabolism of lipids, molecular transportation, cellular function and maintenance, cell morphology and biochemistry of small molecules. CONCLUSIONS: This study identified metabolites, candidate genes and enriched biological functions/processes associated with RFI and its component traits through the integrative analyses of metabolites with phenotypic traits and DNA variants. Our findings could enhance the understanding of biochemical mechanisms of feed efficiency traits and could lead to improvement of genomic prediction accuracy via incorporating metabolite data.

Investigating the genetic architecture of disease resilience in pigs by genome-wide association studies of complete blood count traits collected from a natural disease challenge model.

BACKGROUND: Genetic improvement for disease resilience is anticipated to be a practical method to improve efficiency and profitability of the pig industry, as resilient pigs maintain a relatively undepressed level of performance in the face of infection. However, multiple biological functions are known to be involved in disease resilience and this complexity means that the genetic architecture of disease resilience remains largely unknown. Here, we conducted genome-wide association studies (GWAS) of 465,910 autosomal SNPs for complete blood count (CBC) traits that are important in an animal's disease response. The aim was to identify the genetic control of disease resilience. RESULTS: Univariate and multivariate single-step GWAS were performed on 15 CBC traits measured from the blood samples of 2743 crossbred (Landrace × Yorkshire) barrows drawn at 2-weeks before, and at 2 and 6-weeks after exposure to a polymicrobial infectious challenge. Overall, at a genome-wise false discovery rate of 0.05, five genomic regions located on Sus scrofa chromosome (SSC) 2, SSC4, SSC9, SSC10, and SSC12, were significantly associated with white blood cell traits in response to the polymicrobial challenge, and nine genomic regions on multiple chromosomes (SSC1, SSC4, SSC5, SSC6, SSC8, SSC9, SSC11, SSC12, SSC17) were significantly associated with red blood cell and platelet traits collected before and after exposure to the challenge. By functional enrichment analyses using Ingenuity Pathway Analysis (IPA) and literature review of previous CBC studies, candidate genes located nearby significant single-nucleotide polymorphisms were found to be involved in immune response, hematopoiesis, red blood cell morphology, and platelet aggregation. CONCLUSIONS: This study helps to improve our understanding of the genetic basis of CBC traits collected before and after exposure to a polymicrobial infectious challenge and provides a step forward to improve disease resilience.

Influence of aging on chronic unpredictable mild stress-induced depression-like behavior in male C57BL/6J mice.

Depression is a common psychiatric disorder that can occur throughout an individual's lifespan. Chronic unpredictable mild stress (CUMS) protocol is currently the most commonly used to develop an animal model of depression. Due to the variable duration and procedure of CUMS, it is difficult to reproduce and explore the mechanism of CUMS-induced depression effectively. In the present study, the CUMS-induced behavioral phenotypes were assessed in male C57BL/6J mice at the age of 9-18 weeks. The mice stressed for 3-8 weeks exhibited lower body weight as well as longer immobility time of forced swim and tail suspension test compared to control mice. Moreover, lessening and impairment of hippocampal neurons was found in stressed mice at the age of 18 weeks, which was correlated with increased relative mRNA expression levels of inflammatory cytokines BDNF, Htr1a, and IL-6 in the hippocampus. Nevertheless, no difference between stressed and control mice was observed neither in the sucrose preference nor in the open field test (except for vertical activity in OFT) at the age of 18 weeks. These findings reveal that 3-8 weeks of chronic stress could induce depression-like alterations in male C57BL/6J mice and the behavioral adaptation of aged mice might fail to the availability of the depression model.

Genetic potential for residual feed intake and diet fed during early- to mid-gestation influences post-natal DNA methylation of imprinted genes in muscle and liver tissues in beef cattle.

Discovery of epigenetic modifications associated with feed efficiency or other economically important traits would increase our understanding of the molecular mechanisms underlying these traits. In combination with known genetic markers, this would provide opportunity to improve genomic selection accuracy in cattle breeding programs. It would also allow cattle to be managed to improve favorable gene expression. The objective of this study was to identify variation in DNA methylation between beef cattle of differential pre-natal nutrition and divergent genetic potential for residual feed intake (RFI). Purebred Angus offspring with the genetic potential for either high (HRFI) or low (LRFI) RFI were prenatally exposed to either a restricted maternal diet of 0.5 kg/d average daily gain (ADG) or a moderate maternal diet of 0.7 kg/d ADG from 30 to 150 d of gestation. We performed DNA methylation analysis of differentially methylated regions (DMR) of imprinted genes (Insulin-like growth factor 2 (IGF2) DMR2, IGF2/H19 imprinting control region (ICR) and IGF2 receptor (IGF2R) DMR2) using post-natal samples of longissimus dorsi (LD) muscle taken from male and female calves at birth and weaning, and of LD muscle, semimembranosus (SM) muscle, and liver samples collected from steers at slaughter (17 months of age). Interestingly, for all three DMR investigated in liver, LRFI steers had higher levels of methylation than HRFI steers. In LD muscle, IGF2/H19 ICR methylation differences for heifers at birth were due to pre-natal diet, while for steers at birth they were mostly the result of genetic potential for RFI with LRFI steers again having higher levels of methylation than HRFI steers. While results from repeated measures analysis of DNA methylation in steers grouped by RFI revealed few differences, in steers grouped by diet, we found higher methylation levels of IGF2 DMR2 and IGF2R DMR2 in LD muscle of restricted diet steers at weaning and slaughter than at birth, as well as increased methylation in LD muscle of restricted diet steers compared with moderate diet steers at weaning and/or slaughter. Our results suggest that differential pre-natal nutrition, and divergent genetic potential for RFI, induces tissue- and sex-specific alterations in post-natal IGF2 and IGF2R methylation patterns and that these patterns can vary with age in Angus beef cattle.

Phenotypic and genetic correlations of beef replacement heifer feeding behaviour, feed intake and feed efficiency with cow performance and lifetime productivity.

Objectives were to quantify the phenotypic (rp ) and genetic (rg ) correlations between early-life feeding behaviours, dry matter intake, and feed efficiency and measures of cow performance and lifetime productivity traits. Traits were measured on 1,145 crossbred replacement beef heifers and then on cows over parities one to four. Feeding event duration (FD) was phenotypically correlated with cow prebreeding body weight (PBWT; rp 0.29-0.45), cow prebreeding back fat thickness (PBBF; rp 0.35-0.49), progeny weaning weight (WW; rp 0.09-0.31) and progeny birthweight (BW; rp -0.06 to 0.17). Feeding event frequency (FF) was phenotypically correlated with PBBF (rp 0.16-0.30). Dry matter intake (DMI) was phenotypically correlated with PBWT (rp 0.16-0.20) and PBBF (rp -0.22 to -0.05). Feeding event duration was genetically correlated with PBWT (rg 0.38-0.41). Feeding event frequency was genetically correlated with PBWT (rg -0.43 to -0.39). Dry matter intake was genetically correlated with PBWT (rg -0.27 to 0.14). Days in herd (DIH) was phenotypically correlated with FD and DMI (rp  = 0.12, 0.20, respectively). Lifetime productivity was phenotypically correlated with FD and FF (rg  = 0.25, 0.22, respectively). Calving interval was phenotypically correlated with FD and FF (rp  = -0.12, -0.14, respectively) and genetically correlated with FF (rg  = -0.41). Due to moderate positive correlations with cow weight, caution would be required in selection to prevent an increase in mature cow size. Use of FF, FD, DMI and a measure of feed efficiency such as residual feed intake adjusted for back fat (RFIFAT ) in a balanced selection index is recommended.

Bovine hepatic miRNAome profiling and differential miRNA expression analyses between beef steers with divergent feed efficiency phenotypes.

MicroRNAs (miRNAs) are small RNA molecules involved in regulation of multiple biological processes through modulating expression of their target genes. Here we employed RNAseq to profile liver tissue miRNAome of 60 steers from Angus, Charolais, and Kinsella Composite (KC) populations. Of these animals, 36 animals (n = 12 for each breed) were utilized to identify differentially expressed (DE) miRNAs between animals with high (n = 6) or low (n = 6) phenotypic values of residual feed intake (RFI), a common measurement of feed efficiency. At a threshold of fold-change > 1.5 and P-value < 0.05, we detected 12 (7 up- and 5 downregulated in low-RFI animals), 18 (12 up- and 6 downregulated), and 13 (8 up- and 5 downregulated) DE miRNAs for Angus, Charolais, and KC steers, respectively. Most of the DE miRNAs were breed specific, with bta-miR-449a and bta-miR-AB-2 being differentially expressed in all three breeds. The predicted target genes of the identified DE miRNA are mainly involved in cell cycle, cell death and survival, cell signaling, cellular growth and proliferation, protein trafficking, cell morphology, cell-to-cell signaling and interaction, cellular development, molecular transport, post-translational modification, as well as nutrient metabolism (lipids, carbohydrates, protein and amino acid). Our results provide insights into the bovine hepatic miRNAome and their potential roles in molecular regulation of RFI in beef cattle.

Publisher Correction: Uncovering Sub-Structure and Genomic Profiles in Across-Countries Subpopulations of Angus Cattle.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The treatment of V2 + V3 idiopathic trigeminal neuralgia using peripheral nerve radiofrequency thermocoagulation via the foramen rotundum and foramen ovale compared with semilunar ganglion radiofrequency thermocoagulation.

OBJECTIVES: To compare the advantages and disadvantages of V2 + V3 idiopathic trigeminal neuralgia using peripheral nerve radiofrequency (RF) thermocoagulation (PRF) via the foramen rotundum (FR) and foramen ovale (FO) with those of semilunar ganglion RF thermocoagulation (GRF) under local anesthesia, for exploring a new and available surgical method for patients with V2 + V3 idiopathic trigeminal neuralgia. PATIENTS AND METHODS: 102 patients with V2 + V3 idiopathic trigeminal neuralgia were enrolled in this prospective randomized controlled clinical trial, and they were divided into the PRF and GRF group randomly (n = 51 in both groups). The outcome of pain relief was assessed using the Barrow Neurological Institute (BNI) pain score, and grouped as good (BNI Class I or II, no medication required) and bad (BNI Class III-V, medication required or failed). Recurrence was defined as a relapse to a previous lower level after attainment of any higher level of pain relief. The immediate effective rate, the 2-year postoperative effective rate, the 2-year postoperative recurrence rate, and the number of complications were observed and recorded. RESULTS: Their basic conditions (age, gender ratio, side of pain, and disease duration) were similar. Furthermore, we found that the 2-year postoperative effective rate between them had no significant difference. By comparing the two groups, PRF group had the better immediate effective rate of the V2 branch and no severe complications such as corneal ulcer, however, GRF group had lower 2-year postoperative recurrence rate of the V3 branch and fewer facial swelling. CONCLUSION: The PRF surgery, like GRF, is another prospective treatment for V2 + V3 idiopathic trigeminal neuralgia by virtue of its excellent immediate effect, accurate positioning and high safety.

Uncovering Sub-Structure and Genomic Profiles in Across-Countries Subpopulations of Angus Cattle.

Highlighting genomic profiles for geographically distinct subpopulations of the same breed may provide insights into adaptation mechanisms to different environments, reveal genomic regions divergently selected, and offer initial guidance to joint genomic analysis. Here, we characterized similarities and differences between the genomic patterns of Angus subpopulations, born and raised in Canada (N = 382) and Brazil (N = 566). Furthermore, we systematically scanned for selection signatures based on the detection of autozygosity islands common between the two subpopulations, and signals of divergent selection, via FST and varLD tests. The principal component analysis revealed a sub-structure with a close connection between the two subpopulations. The averages of genomic relationships, inbreeding coefficients, and linkage disequilibrium at varying genomic distances were rather similar across them, suggesting non-accentuated differences in overall genomic diversity. Autozygosity islands revealed selection signatures common to both subpopulations at chromosomes 13 (63.77-65.25 Mb) and 14 (22.81-23.57 Mb), which are notably known regions affecting growth traits. Nevertheless, further autozygosity islands along with FST and varLD tests unravel particular sites with accentuated population subdivision at BTAs 7 and 18 overlapping with known QTL and candidate genes of reproductive performance, thermoregulation, and resistance to infectious diseases. Our findings indicate overall genomic similarity between Angus subpopulations, with noticeable signals of divergent selection in genomic regions associated with the adaptation in different environments.

Genetic architecture of quantitative traits in beef cattle revealed by genome wide association studies of imputed whole genome sequence variants: I: feed efficiency and component traits.

BACKGROUND: Genome wide association studies (GWAS) on residual feed intake (RFI) and its component traits including daily dry matter intake (DMI), average daily gain (ADG), and metabolic body weight (MWT) were conducted in a population of 7573 animals from multiple beef cattle breeds based on 7,853,211 imputed whole genome sequence variants. The GWAS results were used to elucidate genetic architectures of the feed efficiency related traits in beef cattle. RESULTS: The DNA variant allele substitution effects approximated a bell-shaped distribution for all the traits while the distribution of additive genetic variances explained by single DNA variants followed a scaled inverse chi-squared distribution to a greater extent. With a threshold of P-value < 1.00E-05, 16, 72, 88, and 116 lead DNA variants on multiple chromosomes were significantly associated with RFI, DMI, ADG, and MWT, respectively. In addition, lead DNA variants with potentially large pleiotropic effects on DMI, ADG, and MWT were found on chromosomes 6, 14 and 20. On average, missense, 3'UTR, 5'UTR, and other regulatory region variants exhibited larger allele substitution effects in comparison to other functional classes. Intergenic and intron variants captured smaller proportions of additive genetic variance per DNA variant. Instead 3'UTR and synonymous variants explained a greater amount of genetic variance per DNA variant for all the traits examined while missense, 5'UTR and other regulatory region variants accounted for relatively more additive genetic variance per sequence variant for RFI and ADG, respectively. In total, 25 to 27 enriched cellular and molecular functions were identified with lipid metabolism and carbohydrate metabolism being the most significant for the feed efficiency traits. CONCLUSIONS: RFI is controlled by many DNA variants with relatively small effects whereas DMI, ADG, and MWT are influenced by a few DNA variants with large effects and many DNA variants with small effects. Nucleotide polymorphisms in regulatory region and synonymous functional classes play a more important role per sequence variant in determining variation of the feed efficiency traits. The genetic architecture as revealed by the GWAS of the imputed 7,853,211 DNA variants will improve our understanding on the genetic control of feed efficiency traits in beef cattle.

Genetic architecture of quantitative traits in beef cattle revealed by genome wide association studies of imputed whole genome sequence variants: II: carcass merit traits.

BACKGROUND: Genome wide association studies (GWAS) were conducted on 7,853,211 imputed whole genome sequence variants in a population of 3354 to 3984 animals from multiple beef cattle breeds for five carcass merit traits including hot carcass weight (HCW), average backfat thickness (AFAT), rib eye area (REA), lean meat yield (LMY) and carcass marbling score (CMAR). Based on the GWAS results, genetic architectures of the carcass merit traits in beef cattle were elucidated. RESULTS: The distributions of DNA variant allele substitution effects approximated a bell-shaped distribution for all the traits while the distribution of additive genetic variances explained by single DNA variants conformed to a scaled inverse chi-squared distribution to a greater extent. At a threshold of P-value < 10-5, 51, 33, 46, 40, and 38 lead DNA variants on multiple chromosomes were significantly associated with HCW, AFAT, REA, LMY, and CMAR, respectively. In addition, lead DNA variants with potentially large pleiotropic effects on HCW, AFAT, REA, and LMY were found on chromosome 6. On average, missense variants, 3'UTR variants, 5'UTR variants, and other regulatory region variants exhibited larger allele substitution effects on the traits in comparison to other functional classes. The amounts of additive genetic variance explained per DNA variant were smaller for intergenic and intron variants on all the traits whereas synonymous variants, missense variants, 3'UTR variants, 5'UTR variants, downstream and upstream gene variants, and other regulatory region variants captured a greater amount of additive genetic variance per sequence variant for one or more carcass merit traits investigated. In total, 26 enriched cellular and molecular functions were identified with lipid metabolisms, small molecular biochemistry, and carbohydrate metabolism being the most significant for the carcass merit traits. CONCLUSIONS: The GWAS results have shown that the carcass merit traits are controlled by a few DNA variants with large effects and many DNA variants with small effects. Nucleotide polymorphisms in regulatory, synonymous, and missense functional classes have relatively larger impacts per sequence variant on the variation of carcass merit traits. The genetic architecture as revealed by the GWAS will improve our understanding on genetic controls of carcass merit traits in beef cattle.