Molecular Mechanisms Associated with the Development of the Metritis Complex in Dairy Cattle.

The metritis complex (MC), a group of post-partum uterine diseases, is associated with increased treatment costs and reduced milk yield and fertility. The goal of this study was to identify genetic variants, genes, or genomic regions that modulate MC disease. A genome-wide association study was performed using a single-locus mixed linear model of 1967 genotypes (624,460 SNPs) and metritis complex records. Then, in-silico functional analyses were performed to detect biological mechanisms and pathways associated with the development of MC. The ATP8A2, COX16, AMN, and TRAF3 genes, located on chromosomes 12, 10, and 21, were associated with MC at p ≤ 0.0001. These genes are involved in the regulation of cholesterol metabolism in the stromal tissue of the uterus, which can be directly associated with the mode of transmission for pathogens causing the metritis complex. The modulation of cholesterol abundance alters the efficiency of virulence factors and may affect the susceptibility of the host to infection. The SIPA1L1, DEPDC5, and RNF122 genes were also significantly associated with MC at p ≤ 0.0001 and are involved in the PI3k-Akt pathway, responsible for activating the autophagic processes. Thus, the dysregulation of these genes allows for unhindered bacterial invasion, replication, and survival within the endometrium.

Olive- and Coconut-Oil-Enriched Diets Decreased Secondary Bile Acids and Regulated Metabolic and Transcriptomic Markers of Brain Injury in the Frontal Cortexes of NAFLD Pigs.

The objective of this study was to investigate the effect of dietary fatty acid (FA) saturation and carbon chain length on brain bile acid (BA) metabolism and neuronal number in a pig model of pediatric NAFLD. Thirty 20-day-old Iberian pigs, pair-housed in pens, were randomly assigned to receive one of three hypercaloric diets for 10 weeks: (1) lard-enriched (LAR; n = 5 pens), (2) olive-oil-enriched (OLI, n = 5), and (3) coconut-oil-enriched (COC; n = 5). Pig behavior and activity were analyzed throughout the study. All animals were euthanized on week 10 and frontal cortex (FC) samples were collected for immunohistochemistry, metabolomic, and transcriptomic analyses. Data were analyzed by multivariate and univariate statistics. No differences were observed in relative brain weight, neuronal number, or cognitive functioning between diets. Pig activity and FC levels of neuroprotective secondary BAs and betaine decreased in the COC and OLI groups compared with LAR, and paralleled the severity of NAFLD. In addition, OLI-fed pigs showed downregulation of genes involved in neurotransmission, synaptic transmission, and nervous tissue development. Similarly, COC-fed pigs showed upregulation of neurogenesis and myelin repair genes, which caused the accumulation of medium-chain acylcarnitines in brain tissue. In conclusion, our results indicate that secondary BA levels in the FCs of NAFLD pigs are affected by dietary FA composition and are associated with metabolic and transcriptomic markers of brain injury. Dietary interventions that aim to replace saturated FAs by medium-chain or monounsaturated FAs in high-fat hypercaloric diets may have a negative effect on brain health in NAFLD patients.

Genetic parameters and genetic trends for reproductive traits in Egyptian buffalo.

Reproductive traits are important for farm profitability because failure to reproduce is the primary reason for culling animals. Study objectives were to estimate genetic parameters and evaluate the trends for reproductive traits. Age at first calving (AFC), gestation length (GL), postpartum interval to pregnancy (PPIP), calving interval (CI) and calving ease score (CE) were recorded. A total of 38,906 records were available from 2426 buffalo cows. There was evaluation of genetic parameters using three models. The first model was applied to the first three parities fitting animal as a random effect. There was also a repeatability model utilized where data from all parities were evaluated to estimate heritability and repeatability. There was also a bivariate model to estimate genetic correlations between reproductive traits. Heritability estimates ranged from 0.0001 to 0.12 for PPIP and CE, respectively. Repeatability estimates were low to moderate ranging from 0.13 to 0.38 for PPIP and GL, respectively. There were close genetic correlations of 0.99 and - 0.93 between PPIP-CI and GL-CE, respectively. Genetic correlations between the other reproductive traits were low to moderate. Genetic trends for all reproductive traits were negative with and of a small magnitude, and regression coefficients were significant only for AFC and PPIP. The results from the current study supported the urgent need, not only for genetic or genomic selection improvement programs, but also for improving the farm management practices for reproductive traits in Egyptian buffalo.

Evaluation of a genomic-enhanced sorting system for feeder cattle1.

This study evaluated the use of molecular breeding values (MBVs) for carcass traits to sort steers into quality grid and lean meat yield (LMY) groups. A discovery set of 2,609 animals with genotypes and carcass phenotypes was used to predict MBVs for LMY and marbling score (MBS) for 299 Angus, 181 Charolais, and 638 Kinsella Composite steers using genomic best linear unbiased prediction. Steers were sorted in silico into four MBV groups namely Quality (with MBVs greater than the mean for LMY and MBS), Lean (with MBVs greater than the mean for LMY but less than or equal to the mean for MBS), Marbling (with MBVs greater than the mean for MBS but less than or equal to the mean for LMY), and Other (with MBVs lower than the mean for LMY and MBS). Carcass phenotypes on the steers were then collected at slaughter and evaluated for consistency with the assigned MBV groups using descriptive statistics and least square analysis. Accuracy of MBV predictions was assessed by Pearson's correlation between predicted MBV and adjusted phenotype divided by the square root of trait heritability. Genomic breed compositions were predicted for all steers to correct for possible population stratification and breed effects in the test model. The number of steers that met the expected carcass outcome was counted to produce actual percentages for each MBV group. Results showed that on average, Quality and Marbling groups had greater back-fat and more marbling across the three populations while Lean group had leaner carcasses. Carcass weights were similar across MBV groups. Within MBV groups, decreases in variability were observed for most traits suggesting improvement in carcass uniformity. Greater than 70% of the steers in Quality, Lean, and Marbling groups met the Quality Grid and Y1-LMY target for Angus and Charolais but not for Kinsella composite. The accuracy of MBV prediction ranged from 0.43 to 0.59 indicating that up to 35% of the observed carcass trait variability can be predicted, which suggests utility of MBV as a marker-assisted management tool to sort feeder cattle into uniform carcass endpoint groups under similar environmental and management conditions. Further investigation is warranted to evaluate the performance of feeder cattle sorted based on MBV and managed for different carcass endpoints as well as the cost-benefit implications for feedlot operations.

Genome-wide association scan for heterotic quantitative trait loci in multi-breed and crossbred beef cattle.

BACKGROUND: Heterosis has been suggested to be caused by dominance effects. We performed a joint genome-wide association analysis (GWAS) using data from multi-breed and crossbred beef cattle to identify single nucleotide polymorphisms (SNPs) with significant dominance effects associated with variation in growth and carcass traits and to understand the mode of action of these associations. METHODS: Illumina BovineSNP50 genotypes and phenotypes for 11 growth and carcass traits were available for 6796 multi-breed and crossbred beef cattle. After performing quality control, 42,610 SNPs and 6794 animals were used for further analyses. A single-SNP GWAS for the joint association of additive and dominance effects was conducted in purebred, crossbred, and combined datasets using the ASReml software. Genomic breed composition predicted from admixture analyses was included in the mixed effect model to account for possible population stratification and breed effects. A threshold of 10% genome-wide false discovery rate was applied to declare associations as significant. The significant SNPs with dominance association were mapped to their corresponding genes at 100 kb. RESULTS: Seven SNPs with significant dominance associations were detected for birth weight, weaning weight, pre-weaning daily gain, yearling weight and marbling score across the three datasets at a false discovery rate of 10%. These SNPs were located on bovine chromosomes 1, 3, 4, 6 and 21 and mapped to six putative candidate genes: U6atac, AGBL4, bta-mir-2888-1, REPIN1, ICA1 and NXPH1. These genes have interesting biological functions related to the regulation of gene expression, glucose and lipid metabolism and body fat mass. For most of the identified loci, we observed over-dominance association with the studied traits, such that the heterozygous individuals at any of these loci had greater genotypic values for the trait than either of the homozygous individuals. CONCLUSIONS: Our results revealed very few regions with significant dominance genetic effects across all the traits studied in the three datasets used. Regarding the SNPs that were detected with dominance associations, further investigation is needed to determine their relevance in crossbreeding programs assuming that dominance effects are the main cause of (or contribute usefully to) heterosis.

Modeling heterotic effects in beef cattle using genome-wide SNP-marker genotypes.

An objective of commercial beef cattle crossbreeding programs is to simultaneously optimize use of additive (breed differences) and non-additive (heterosis) effects. A total of 6,794 multibreed and crossbred beef cattle with phenotype and Illumina BovineSNP50 genotype data were used to predict genomic heterosis for growth and carcass traits by applying two methods assumed to be linearly proportional to heterosis. The methods were as follows: 1) retained heterozygosity predicted from genomic breed fractions (HET1) and 2) deviation of adjusted crossbred phenotype from midparent value (HET2). Comparison of methods was based on prediction accuracy from cross-validation. Here, a mutually exclusive random sampling of all crossbred animals (n = 5,327) was performed to form five groups replicated five times with approximately 1,065 animals per group. In each run within a replicate, one group was assigned as a validation set, while the remaining four groups were combined to form the reference set. The phenotype of the animals in the validation set was assumed to be unknown; thus, it resulted in every animal having heterosis values that were predicted without using its own phenotype, allowing their adjusted phenotype to be used for validation. The same approach was used to test the impact of predicted heterosis on accuracy of genomic breeding values (GBV). The results showed positive heterotic effects for growth traits but not for carcass traits that reflect the importance of heterosis for growth traits in beef cattle. Heterosis predicted by HET1 method resulted in less variable estimates that were mostly within the range of estimates generated by HET2. Prediction accuracy was greater for HET2 (0.37-0.98) than HET1 (0.34-0.43). Proper consideration of heterosis in genomic evaluation models has debatable effects on accuracy of EBV predictions. However, opportunity exists for predicting heterosis, improving accuracy of genomic selection, and consequently optimizing crossbreeding programs in beef cattle.

Genome-wide association studies and genomic prediction of breeding values for calving performance and body conformation traits in Holstein cattle.

BACKGROUND: Our aim was to identify genomic regions via genome-wide association studies (GWAS) to improve the predictability of genetic merit in Holsteins for 10 calving and 28 body conformation traits. Animals were genotyped using the Illumina Bovine 50 K BeadChip and imputed to the Illumina BovineHD BeadChip (HD). GWAS were performed on 601,717 real and imputed single nucleotide polymorphism (SNP) genotypes using a single-SNP mixed linear model on 4841 Holstein bulls with breeding value predictions and followed by gene identification and in silico functional analyses. The association results were further validated using five scenarios with different numbers of SNPs. RESULTS: Seven hundred and eighty-two SNPs were significantly associated with calving performance at a genome-wise false discovery rate (FDR) of 5%. Most of these significant SNPs were on chromosomes 18 (71.9%), 17 (7.4%), 5 (6.8%) and 7 (2.4%) and mapped to 675 genes, among which 142 included at least one significant SNP and 532 were nearby one (100 kbp). For body conformation traits, 607 SNPs were significant at a genome-wise FDR of 5% and most of them were located on chromosomes 5 (30%), 18 (27%), 20 (13%), 6 (6%), 7 (5%), 14 (5%) and 13 (3%). SNP enrichment functional analyses for calving traits at a FDR of 1% suggested potential biological processes including musculoskeletal movement, meiotic cell cycle, oocyte maturation and skeletal muscle contraction. Furthermore, pathway analyses suggested potential pathways associated with calving performance traits including tight junction, oxytocin signaling, and MAPK signaling (P < 0.10). The prediction ability of the 1206 significant SNPs was between 78 and 83% of the prediction ability of the BovineSNP50 SNPs for calving performance traits and between 35 and 79% for body conformation traits. CONCLUSIONS: Various SNPs that are significantly associated with calving performance are located within or nearby genes with potential roles in tight junction, oxytocin signaling, and MAPK signaling. Combining the significant SNPs or SNPs within or nearby gene(s) from the HD panel with the BovineSNP50 panel yielded a marginal increase in the accuracy of prediction of genomic estimated breeding values for all traits compared to the use of the BovineSNP50 panel alone.

Genome-wide association for milk production and female fertility traits in Canadian dairy Holstein cattle.

BACKGROUND: Genome-wide association studies (GWAS) are a powerful tool for detecting genomic regions explaining variation in phenotype. The objectives of the present study were to identify or refine the positions of genomic regions affecting milk production, milk components and fertility traits in Canadian Holstein cattle, and to use these positions to identify genes and pathways that may influence these traits. RESULT: Several QTL regions were detected for milk production (MILK), fat production (FAT), protein production (PROT) and fat and protein deviation (FATD, PROTD respectively). The identified QTL regions for production traits (including milk production) support previous findings and some overlap with genes with known relevant biological functions identified in earlier studies such as DGAT1 and CPSF1. A significant region on chromosome 21 overlapping with the gene FAM181A and not previous linked to fertility in dairy cattle was identified for the calving to first service interval and days open. A functional enrichment analysis of the GWAS results yielded GO terms consistent with the specific phenotypes tested, for example GO terms GO:0007595 (lactation) and GO:0043627 (response to estrogen) for milk production (MILK), GO:0051057 (positive regulation of small GTPase mediated signal transduction) for fat production (FAT), GO:0040019 (positive regulation of embryonic development) for first service to calving interval (CTFS) and GO:0043268 (positive regulation of potassium ion transport) for days open (DO). In other cases the connection between the enriched GO terms and the traits were less clear, for example GO:0003279 (cardiac septum development) for FAT and GO:0030903 (notochord development) for DO trait. CONCLUSION: The chromosomal regions and enriched pathways identified in this study confirm several previous findings and highlight new regions and pathways that may contribute to variation in production or fertility traits in dairy cattle.

Single nucleotide polymorphisms for feed efficiency and performance in crossbred beef cattle.

BACKGROUND: This study was conducted to: (1) identify new SNPs for residual feed intake (RFI) and performance traits within candidate genes identified in a genome wide association study (GWAS); (2) estimate the proportion of variation in RFI explained by the detected SNPs; (3) estimate the effects of detected SNPs on carcass traits to avoid undesirable correlated effects on these economically important traits when selecting for feed efficiency; and (4) map the genes to biological mechanisms and pathways. A total number of 339 SNPs corresponding to 180 genes were tested for association with phenotypes using a single locus regression (SLRM) and genotypic model on 726 and 990 crossbred animals for feed efficiency and carcass traits, respectively. RESULTS: Strong evidence of associations for RFI were located on chromosomes 8, 15, 16, 18, 19, 21, and 28. The strongest association with RFI (P = 0.0017) was found with a newly discovered SNP located on BTA 8 within the ELP3 gene. SNPs rs41820824 and rs41821600 on BTA 16 within the gene HMCN1 were strongly associated with RFI (P = 0.0064 and P = 0.0033, respectively). A SNP located on BTA 18 within the ZNF423 gene provided strong evidence for association with RFI (P = 0.0028). Genomic estimated breeding values (GEBV) from 98 significant SNPs were moderately correlated (0.47) to the estimated breeding values (EBVs) from a mixed animal model. The significant (P < 0.05) SNPs (98) explained 26% of the genetic variance for RFI. In silico functional analysis for the genes suggested 35 and 39 biological processes and pathways, respectively for feed efficiency traits. CONCLUSIONS: This study identified several positional and functional candidate genes involved in important biological mechanisms associated with feed efficiency and performance. Significant SNPs should be validated in other populations to establish their potential utilization in genetic improvement programs.