Metabolomics uses advanced analytical chemistry techniques to comprehensively measure large numbers of small molecule metabolites in cells, tissues and biofluids. The ability to rapidly detect and ...quantify hundreds or even thousands of metabolites within a single sample is helping scientists paint a far more complete picture of system-wide metabolism and biology. Metabolomics is also allowing researchers to focus on measuring the end-products of complex, hard-to-decipher genetic, epigenetic and environmental interactions. As a result, metabolomics has become an increasingly popular "omics" approach to assist with the robust phenotypic characterization of humans, crop plants and model organisms. Indeed, metabolomics is now routinely used in biomedical, nutritional and crop research. It is also being increasingly used in livestock research and livestock monitoring. The purpose of this systematic review is to quantitatively and objectively summarize the current status of livestock metabolomics and to identify emerging trends, preferred technologies and important gaps in the field. In conducting this review we also critically assessed the applications of livestock metabolomics in key areas such as animal health assessment, disease diagnosis, bioproduct characterization and biomarker discovery for highly desirable economic traits (i.e., feed efficiency, growth potential and milk production). A secondary goal of this critical review was to compile data on the known composition of the livestock metabolome (for 5 of the most common livestock species namely cattle, sheep, goats, horses and pigs). These data have been made available through an open access, comprehensive livestock metabolome database (LMDB, available at http://www.lmdb.ca). The LMDB should enable livestock researchers and producers to conduct more targeted metabolomic studies and to identify where further metabolome coverage is needed.
The symbiotic rumen microbiota is essential for the digestion of plant fibers and contributes to the variation of production and health traits in ruminants. However, to date, the heritability of ...rumen microbial features and host genetic components associated with the rumen microbiota, as well as whether such genetic components are animal performance relevant, are largely unknown.
In the present study, we assessed rumen microbiota from a cohort of 709 beef cattle and showed that multiple factors including breed, sex, and diet drove the variation of rumen microbiota among animals. The diversity indices, the relative abundance of ~ 34% of microbial taxa (59 out of 174), and the copy number of total bacteria had a heritability estimate (h
) ≥ 0.15, suggesting that they are heritable elements affected by host additive genetics. These moderately heritable rumen microbial features were also found to be associated with host feed efficiency traits and rumen metabolic measures (volatile fatty acids). Moreover, 19 single nucleotide polymorphisms (SNPs) located on 12 bovine chromosomes were found to be associated with 14 (12 of them had h
≥ 0.15) rumen microbial taxa, and five of these SNPs were known quantitative trait loci for feed efficiency in cattle.
These findings suggest that some rumen microbial features are heritable and could be influenced by host genetics, highlighting a potential to manipulate and obtain a desirable and efficient rumen microbiota using genetic selection and breeding. It could be a useful strategy to further improve feed efficiency and optimize rumen fermentation through targeting both cattle and their rumen microbiota.
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.
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
), 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.
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.
Genomic selection can be considered as an effective tool for developing breeding programs in American mink. However, the genetic gains for economically important traits can be influenced by the ...accuracy of genomic predictions. The objective of this study was to investigate the prediction accuracies of traditional best linear unbiased prediction (BLUP), multi-step genomic BLUP (GBLUP) and single-step GBLUP (ssGBLUP) methods in American mink using simulated data with different levels of heritability, marker density, training set (TS) sizes and selection designs based on either phenotypic performance or estimated breeding values (EBVs). Under EBV selection design, the accuracy of BLUP predictions was increased by 38% and 44% for h2 = 0.10, 27% and 29% for h2 = 0.20, and 5.8% and 6% for h2 = 0.50 using GBLUP and ssGBLUP methods, respectively. Under phenotypic selection design, the accuracies of prediction by ssGBLUP method were 11.8% and 15.4% higher than those obtained by GBLUP for heritability of 0.10 and 0.20, respectively. However, the efficiency of ssGBLUP and GBLUP was not influenced by selection design at higher level of heritability (h2 = 0.50). Furthermore, higher selection intensity increased the bias of predictions in both pedigree-based and genomic evaluations. Regardless of selection design, TS sizes for GBLUP and ssGBLUP methods should be at least 3000 to achieve more accuracy than using BLUP for heritability of 0.50 and marker density of 10k and 50k. Overall, more accurate predictions were obtained using ssGBLUP method particularly for lowly heritable traits and low density of markers. Our results indicated that TS sizes should be optimized in accordance with heritability level, marker density, selection design and prediction method for genomic selection in American mink. The results provided an initial framework for designing genomic selection in mink breeding programs.
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
), 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.
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.
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.
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.
The objective of this study was to extract novel phenotypes related to disease resilience using daily feed intake data from growing pigs under a multifactorial natural disease challenge that was ...designed to mimic a commercial environment with high disease pressure to maximize expression of resilience. Data used were the first 1,341 crossbred wean-to-finish pigs from a research facility in Québec, Canada. The natural challenge was established under careful veterinary oversight by seeding the facility with diseased pigs from local health-challenged farms, targeting various viral and bacterial diseases, and maintaining disease pressure by entering batches of 60-75 pigs in a continuous flow system. Feed intake (FI) is sensitive to disease, as pigs tend to eat less when they become ill. Four phenotypes were extracted from the individual daily FI data during finishing as novel measures of resilience. The first two were daily variability in FI or FI duration, quantified by the root mean square error (RMSE) from the within individual regressions of FI or duration at the feeder (DUR) on age (RMSE
and RMSE
). The other two were the proportion of off-feed days, classified based on negative residuals from a 5% quantile regression (QR) of daily feed intake or duration data on age across all pigs (QR
and QR
). Mortality and treatment rate had a heritability of 0.13 (±0.05) and 0.29 (±0.07), respectively. Heritability estimates for RMSE
, RMSE
, QR
, and QR
were 0.21 (±0.07) 0.26 (±0.07), 0.15 (±0.06), and 0.23 (±0.07), respectively. Genetic correlations of RMSE and QR measures with mortality and treatment rate ranged from 0.37 to 0.85, with QR measures having stronger correlations with both. Estimates of genetic correlations of RMSE measures with production traits were typically low, but often favorable (e.g., -0.31 between RMSE
and finishing ADG). Although disease resilience was our target, fluctuations in FI and duration can be caused by many factors other than disease and should be viewed as overall indicators of general resilience to a variety of stressors. In conclusion, daily variation in FI or duration at the feeder can be used as heritable measures of resilience.
Porcine circovirus 2 (PCV2) is a circular single-stranded DNA virus responsible for a group of diseases collectively known as PCV2 Associated Diseases (PCVAD). Variation in the incidence and severity ...of PCVAD exists between pigs suggesting a host genetic component involved in pathogenesis. A large-scale genome-wide association study of experimentally infected pigs (n = 974), provided evidence of a host genetic role in PCV2 viremia, immune response and growth during challenge. Host genotype explained 64% of the phenotypic variation for overall viral load, with two major Quantitative Trait Loci (QTL) identified on chromosome 7 (SSC7) near the swine leukocyte antigen complex class II locus and on the proximal end of chromosome 12 (SSC12). The SNP having the strongest association, ALGA0110477 (SSC12), explained 9.3% of the genetic and 6.2% of the phenotypic variance for viral load. Dissection of the SSC12 QTL based on gene annotation, genomic and RNA-sequencing, suggested that a missense mutation in the SYNGR2 (SYNGR2 p.Arg63Cys) gene is potentially responsible for the variation in viremia. This polymorphism, located within a protein domain conserved across mammals, results in an amino acid variant SYNGR2 p.63Cys only observed in swine. PCV2 titer in PK15 cells decreased when the expression of SYNGR2 was silenced by specific-siRNA, indicating a role of SYNGR2 in viral replication. Additionally, a PK15 edited clone generated by CRISPR-Cas9, carrying a partial deletion of the second exon that harbors a key domain and the SYNGR2 p.Arg63Cys, was associated with a lower viral titer compared to wildtype PK15 cells (>24 hpi) and supernatant (>48hpi)(P < 0.05). Identification of a non-conservative substitution in this key domain of SYNGR2 suggests that the SYNGR2 p.Arg63Cys variant may underlie the observed genetic effect on viral load.
We report the sequencing at 131× coverage, de novo assembly and analyses of the genome of a female Tibetan wild boar. We also resequenced the whole genomes of 30 Tibetan wild boars from six major ...distributed locations and 18 geographically related pigs in China. We characterized genetic diversity, population structure and patterns of evolution. We searched for genomic regions under selection, which includes genes that are involved in hypoxia, olfaction, energy metabolism and drug response. Comparing the genome of Tibetan wild boar with those of neighboring Chinese domestic pigs further showed the impact of thousands of years of artificial selection and different signatures of selection in wild boar and domestic pig. We also report genetic adaptations in Tibetan wild boar that are associated with high altitudes and characterize the genetic basis of increased salivation in domestic pig.
Abstract
The objective was to estimate the genetic parameters of performance and resilience of growing pigs under disease. Data were from 3,139 Yorkshire × Landrace wean-to-finish pigs that were ...exposed to a natural polymicrobial disease challenge that was established by entering naturally infected animals into a nursery barn, targeting various viral and bacterial diseases. The challenge was maintained by entering batches of 60 or 75 healthy nursery pigs every 3 wk in a continuous flow system. Traits analyzed included average daily gain (ADG), feed intake (ADFI) and duration (ADFD); feed conversion ratio (FCR); residual feed intake (RFI); mortality (MOR); number of health treatments (TRT); health scores (HScore); carcass weight (CWT), back fat (CBF) and loin depth (CLD); dressing percentage (DRS); lean yield (LYLD); day-to-day variation in feed intake and duration (VARFI and VARDUR); and the proportion of off-feed days (OFFFI and OFFDUR). Analyses were performed by mixed linear models with genomic relationships. The resilience traits, such as TRT, MOR, and HScore, were lowly heritable (up to 0.15) but had high genetic correlations with each other. Performance traits, such as ADG, ADFI, ADFD, FCR, RFI, and carcass traits, were moderate to highly heritable (0.17 to 0.49). Heritabilities of resilience indicator traits such as OFF and VAR had low to moderate heritabilities (0.08 to 0.23) but were higher when based on duration vs. amount. ADFI had a low genetic correlation with ADFD (0.13). ADG in the challenge nursery had stronger negative genetic correlations with both TRT and MOR than ADG in the finisher (−0.37 to −0.74 vs. −0.15 to −0.56). ADFI and FCR had moderate negative (−0.21 to −0.39) and positive (0.34 to 0.49) genetic correlations, respectively, with TRT and MOR. ADFD and RFI had very low genetic correlations with TRT and MOR. CWT and DRS were moderately negatively correlated with TRT and MOR (−0.33 to −0.59). Resilience indicator traits based on feed intake or duration had moderate to high positive genetic correlations with TRT (0.18 to 0.81) and MOR (0.33 to 0.87). In conclusion, performance and resilience traits under a polymicrobial disease challenge are heritable and can be changed by selection. Phenotypes extracted from feed intake patterns can be used as genetic indicator traits for disease resilience. Most promising is day-to-day variation in intake duration, which had a sizeable heritability (0.23) and favorable genetic correlations with MOR (0.79) and treatment rate (0.20).
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