Bias, dispersion, and accuracy of genomic predictions for feedlot and carcase traits in Australian Angus steers.

BACKGROUND: Improving feedlot performance, carcase weight and quality is a primary goal of the beef industry worldwide. Here, we used data from 3408 Australian Angus steers from seven years of birth (YOB) cohorts (2011-2017) with a minimal level of sire linkage and that were genotyped for 45,152 SNPs. Phenotypic records included two feedlot and five carcase traits, namely average daily gain (ADG), average daily dry matter intake (DMI), carcase weight (CWT), carcase eye muscle area (EMA), carcase Meat Standard Australia marbling score (MBL), carcase ossification score (OSS) and carcase subcutaneous rib fat depth (RIB). Using a 7-way cross-validation based on YOB cohorts, we tested the quality of genomic predictions using the linear regression (LR) method compared to the traditional method (Pearson's correlation between the genomic estimated breeding value (GEBV) and its associated adjusted phenotype divided by the square root of heritability); explored the factors, such as heritability, validation cohort, and phenotype that affect estimates of accuracy, bias, and dispersion calculated with the LR method; and suggested a novel interpretation for translating differences in accuracy into phenotypic differences, based on GEBV quartiles (Q1Q4). RESULTS: Heritability (h2) estimates were generally moderate to high (from 0.29 for ADG to 0.53 for CWT). We found a strong correlation (0.73, P-value < 0.001) between accuracies using the traditional method and those using the LR method, although the LR method was less affected by random variation within and across years and showed a better ability to discriminate between extreme GEBV quartiles. We confirmed that bias of GEBV was not significantly affected by h2, validation cohort or trait. Similarly, validation cohort was not a significant source of variation for any of the GEBV quality metrics. Finally, we observed that the phenotypic differences were larger for higher accuracies. CONCLUSIONS: Our estimates of h2 and GEBV quality metrics suggest a potential for accurate genomic selection of Australian Angus for feedlot performance and carcase traits. In addition, the Q1Q4 measure presented here easily translates into possible gains of genomic selection in terms of phenotypic differences and thus provides a more tangible output for commercial beef cattle producers.

ImmuneDEX: a strategy for the genetic improvement of immune competence in Australian Angus cattle.

In animal breeding and genetics, the ability to cope with disease, here defined as immune competence (IC), with minimal detriment to growth and fertility is a desired objective which addresses both animal production and welfare considerations. However, defining and objectively measuring IC phenotypes using testing methods which are practical to apply on-farm has been challenging. Based on previously described protocols, we measured both cell-mediated immune response (Cell-IR) and antibody-mediated immune response (Ab-IR) and combined these measures to determine an animal's IC. Using a population of 2,853 Australian Angus steers and heifers, we compared 2 alternative methods to combine both metrics into a single phenotype to be used as a tool for the genetic improvement of IC. The first method, named ZMEAN, is obtained by taking the average of the individual metrics after subjecting each to a Z-score standardization. The second, ImmuneDEX (IDEX), is a weighted average that considers the correlation between Cell-IR and Ab-IR, as well as the difference in ranking of individuals by each metric, and uses these as weights in the averaging. Both simulation and real data were used to understand the behavior of ZMEAN and IDEX. To further ascertain the relationship between IDEX and other traits of economic importance, we evaluated a range of traits related to growth, feedlot performance, and carcass characteristics. We report estimates of heritability of 0.31 ± 0.06 for Cell-IR, 0.42 ± 0.06 for Ab-IR, 0.42 ± 0.06 for ZMEAN and 0.370 ± 0.06 for IDEX, as well as a unity genetic correlation (rg) between ZMEAN and IDEX. While a moderately positive rg was estimated between Cell-IR and Ab-IR (rg = 0.33 ± 0.12), strongly positive estimates were obtained between IDEX and Cell-IR (rg = 0.80 ± 0.05) and between IDEX and Ab-IR (rg = 0.85 ± 0.04). We obtained a moderately negative rg between IC traits and growth including an rg = -0.38 ± 0.14 between IDEX and weaning weight, and negligible with carcass fat measurements, including an rg = -0.03 ± 0.12 between IDEX and marbling. Given that breeding with a sole focus on production might inadvertently increase susceptibility to disease and associated antibiotic use, our analyses suggest that ImmuneDEX will provide a basis to breed animals that are both highly productive and with an enhanced ability to resist disease.

Associations between immune competence phenotype and feedlot health and productivity in Angus cattle.

Genetic strategies aimed at improving general immune competence (IC) have the potential to reduce the incidence and severity of disease in beef production systems, with resulting benefits of improved animal health and welfare and reduced reliance on antibiotics to prevent and treat disease. Implementation of such strategies first requires that methodologies be developed to phenotype animals for IC and demonstration that these phenotypes are associated with health outcomes. We have developed a methodology to identify IC phenotypes in beef steers during the yard weaning period, which is both practical to apply on-farm and does not restrict the future sale of tested animals. In the current study, a total of 838 Angus steers, previously IC phenotyped at weaning, were categorized as low (n = 98), average (n = 653), or high (n = 88) for the IC phenotype. Detailed health and productivity data were collected on all steers during feedlot finishing, and associations between IC phenotype, health outcomes, and productivity were investigated. A favorable association between IC phenotype and number of mortalities during feedlot finishing was observed with higher mortalities recorded in low IC steers (6.1%) as compared with average (1.2%, P < 0.001) or high (0%, P = 0.018) IC steers. Disease incidence was numerically highest in low IC steers (15.3 cases/100 animals) and similar in average IC steers (10.1 cases/100 animals) and high IC steers (10.2 cases/100 animals); however, differences between groups were not significant. No significant influence of IC phenotype on average daily gain was observed, suggesting that selection for improved IC is unlikely to incur a significant penalty to production. The potential economic benefits of selecting for IC in the feedlot production environment were calculated. Health-associated costs were calculated as the sum of lost production costs, lost capital investment costs, and disease treatment costs. Based on these calculations, health-associated costs were estimated at AUS$103/head in low IC steers, AUS$25/head in average IC steers, and AUS$4/head in high IC steers, respectively. These findings suggest that selection for IC has the potential to reduce mortalities during feedlot finishing and, as a consequence, improve the health and welfare of cattle in the feedlot production environment and reduce health-associated costs incurred by feedlot operators.

Immune competence traits assessed during the stress of weaning are heritable and favorably genetically correlated with temperament traits in Angus cattle1.

Selection for production traits with little or no emphasis on health-related traits has the potential to increase susceptibility to disease in food-producing animals. A possible genetic strategy to mitigate such effects is to include both production and health traits in the breeding objective when selecting animals. For this to occur, reliable methodologies are required to assess beneficial health traits, such as the immune capacity of animals. We describe here a methodology to assess the immune competence of beef cattle which is both practical to apply on farm and does not restrict the future sale of tested animals. The methodology also accommodates variation in prior vaccination history of cohorts of animals being tested. In the present study, the immune competence phenotype of 1,100 Angus calves was assessed during yard weaning. Genetic parameters associated with immune competence traits were estimated and associations between immune competence, temperament, and stress-coping ability traits were investigated. Results suggested that immune competence traits, related to an animal's ability to mount both antibody and cell-mediated immune responses, are moderately heritable (h2 = 0.32 ± 0.09 and 0.27 ± 0.08, respectively) and favorably genetically correlated with the temperament trait, flight time (r = 0.63 ± 0.31 and 0.60 ± 0.29 with antibody and cell-mediated immune responses, respectively). Development of methodologies to assess the immune competence phenotype of beef cattle is a critical first step in the establishment of genetic selection strategies aimed at improving the general disease resistance of beef herds. Strategies aimed at reducing the incidence of disease in beef cattle are expected to significantly improve animal health and welfare, reduce reliance on the use of antibiotics to treat disease, and reduce disease-associated costs incurred by producers.

A comparison of transcriptomic patterns measured in the skin of Chinese fine and coarse wool sheep breeds.

We characterised wool traits, and skin gene expression profiles of fine wool Super Merino (SM) and coarse wool Small Tail Han (STH) sheep. SM sheep had a significantly higher total density of wool follicles, heavier fleeces, finer fibre diameter, and increased crimp frequency, staple length and wool grease (lanolin) production. We found 435 genes were expressed at significantly different levels in the skin of the two breeds (127 genes more highly in SM and 308 genes more highly in STH sheep). Classification of the genes more highly expressed in SM sheep revealed numerous lipid metabolic genes as well as genes encoding keratins, keratin-associated proteins, and wool follicle stem cell markers. In contrast, mammalian epidermal development complex genes and other genes associated with skin cornification and muscle function were more highly expressed in STH sheep. Genes identified in this study may be further evaluated for inclusion in breeding programs, or as targets for therapeutic or genetic interventions, aimed at altering wool quality or yield. Expression of the lipid metabolic genes in the skin of sheep may be used as a novel trait with the potential to alter the content or properties of lanolin or the fleece.

Phenobarbital induction and chemical synergism demonstrate the role of UDP-glucuronosyltransferases in detoxification of naphthalophos by Haemonchus contortus larvae.

We used an enzyme induction approach to study the role of detoxification enzymes in the interaction of the anthelmintic compound naphthalophos with Haemonchus contortus larvae. Larvae were treated with the barbiturate phenobarbital, which is known to induce the activity of a number of detoxification enzymes in mammals and insects, including cytochromes P450 (CYPs), UDP-glucuronosyltransferases (UDPGTs), and glutathione (GSH) S-transferases (GSTs). Cotreatment of larvae with phenobarbital and naphthalophos resulted in a significant increase in the naphthalophos 50% inhibitory concentration (IC50) compared to treatment of larvae with the anthelmintic alone (up to a 28-fold increase). The phenobarbital-induced drug tolerance was reversed by cotreatment with the UDPGT inhibitors 5-nitrouracil, 4,6-dihydroxy-5-nitropyrimidine, probenecid, and sulfinpyrazone. Isobologram analysis of the interaction of 5-nitrouracil with naphthalophos in phenobarbital-treated larvae clearly showed the presence of strong synergism. The UDPGT inhibitors 5-nitrouracil, 4,6-dihydroxy-5-nitropyrimidine, and probenecid also showed synergistic effects with non-phenobarbital-treated worms (synergism ratio up to 3.2-fold). This study indicates that H. contortus larvae possess one or more UDPGT enzymes able to detoxify naphthalophos. In highlighting the protective role of this enzyme group, this study reveals the potential for UDPGT enzymes to act as a resistance mechanism that may develop under drug selection pressure in field isolates of this species. In addition, the data indicate the potential for a chemotherapeutic approach utilizing inhibitors of UDPGT enzymes as synergists to increase the activity of naphthalophos against parasitic worms and to combat detoxification-mediated drug resistance if it arises in the field.

A one shot blood phenotype can identify sheep that resist Haemonchus contortus challenge.

Gastrointestinal nematodes remain a major limitation to the productivity of livestock systems. Selective breeding to produce populations that have an enhanced ability to resist infection is a viable and ongoing option to reduce this impact. The development of new phenotypes that facilitate this process is therefore of great interest. For this reason we explored relationships between haematological parameters and the ability of sheep to resist nematode infection. A multivariate analytical approach was used to define algorithms based on the blood parameters that can be used to rank the ability of sheep to resist nematode infection in a single blood sample and can be applied independent of infection status. The algorithms were shown to classify susceptible sheep with a 100% accuracy and resistant sheep with 80% accuracy. Further development of this platform approach may be an important advance for small ruminant production systems worldwide and might also be applied to other diseases of livestock or even environmental stressors such as heat.

Sensory rewiring in an echolocator: genome-wide modification of retinogenic and auditory genes in the bat Myotis davidii.

Bats comprise 20% of all mammalian species and display a number of characteristics, including true flight, echolocation, and a heightened ability to resist viral load that uniquely position this group for comparative genomic studies. Here we searched for evidence of genomic variation consistent with sensory rewiring through bat evolution. We focused on two species with divergent sensory preferences. Myotis davidii is a bat species that echolocates and possesses dim- but not daylight-adapted vision whereas the black flying fox (Pteropus alecto) has highly developed day vision but does not echolocate. Using the naked mole rat as a reference, we found five functional genes (CYP1A2, RBP3, GUCY2F, CRYBB1, and GRK7) encoding visual proteins that have degenerated into pseudogenes in M. davidii but not P. alecto. In a second approach genome-wide codon usage bias (CUB) was compared between the two bat species. This CUB ranking systematically enriched for vision-related (CLN8, RD3, IKZF1, LAMC3, CRX, SOX8, VAX2, HPS1, RHO, PRPH2, and SOX9) and hearing-related (TPRN, TMIE, SLC52A3, OTOF, WFS1, SOD1, TBX18, MAP1A, OTOS, GPX1, and USH1G) machinery in M. davidii but not P. alecto. All vision and hearing genes selectively enriched in M. davidii for which orthologs could be identified also were more biased in the echolocating M. lucifugus than the nonecholocating P. vampyrus. We suggest that the existence of codon bias in vision- and hearing-related genes in a species that has evolved echolocation implies CUB is part of evolution's toolkit to rewire sensory systems. We propose that the two genetic changes (pseudogene formation and CUB) collectively paint a picture of that incorporates a combination of destruction and gain-of-function. Together, they help explain how natural selection has reduced physiological costs associated with the development of a smaller eye poorly adapted to day vision but that also contribute to enhanced dim light vision and the hearing adaptations consonant with echolocation.

The sheep genome illuminates biology of the rumen and lipid metabolism.

Sheep (Ovis aries) are a major source of meat, milk, and fiber in the form of wool and represent a distinct class of animals that have a specialized digestive organ, the rumen, that carries out the initial digestion of plant material. We have developed and analyzed a high-quality reference sheep genome and transcriptomes from 40 different tissues. We identified highly expressed genes encoding keratin cross-linking proteins associated with rumen evolution. We also identified genes involved in lipid metabolism that had been amplified and/or had altered tissue expression patterns. This may be in response to changes in the barrier lipids of the skin, an interaction between lipid metabolism and wool synthesis, and an increased role of volatile fatty acids in ruminants compared with nonruminant animals.

RNF14 is a regulator of mitochondrial and immune function in muscle.

BACKGROUND: Muscle development and remodelling, mitochondrial physiology and inflammation are thought to be inter-related and to have implications for metabolism in both health and disease. However, our understanding of their molecular control is incomplete. RESULTS: In this study we have confirmed that the ring finger 14 protein (RNF14), a poorly understood transcriptional regulator, influences the expression of both mitochondrial and immune-related genes. The prediction was based on a combination of network connectivity and differential connectivity in cattle (a non-model organism) and mice data sets, with a focus on skeletal muscle. They assigned similar probability to mammalian RNF14 playing a regulatory role in mitochondrial and immune gene expression. To try and resolve this apparent ambiguity we performed a genome-wide microarray expression analysis on mouse C2C12 myoblasts transiently transfected with two Rnf14 transcript variants that encode 2 naturally occurring but different RNF14 protein isoforms. The effect of both constructs was significantly different to the control samples (untransfected cells and cells transfected with an empty vector). Cluster analyses revealed that transfection with the two Rnf14 constructs yielded discrete expression signatures from each other, but in both cases a substantial set of genes annotated as encoding proteins related to immune function were perturbed. These included cytokines and interferon regulatory factors. Additionally, transfection of the longer transcript variant 1 coordinately increased the expression of 12 (of the total 13) mitochondrial proteins encoded by the mitochondrial genome, 3 of which were significant in isolated pair-wise comparisons (Mt-coxII, Mt-nd2 and mt-nd4l). This apparent additional mitochondrial function may be attributable to the RWD protein domain that is present only in the longer RNF14 isoform. CONCLUSIONS: RNF14 influences the expression of both mitochondrial and immune related genes in a skeletal muscle context, and has likely implications for the inter-relationship between bioenergetic status and inflammation.

Recombinant production of antimicrobial peptides in heterologous microbial systems.

The emergence and rapid horizontal spread of antibiotic-resistant traits in bacteria of human and veterinary clinical significance has been a driving force in the search for new classes of antibiotics. Recent studies have shown that AMPs (antimicrobial peptides) potentially have a role in addressing this problem. These AMPs are produced naturally by a diverse array of organisms, including bacteria, plants, insects, fish and mammals. Given this diversity, researchers trying to perform comparative studies on AMPs are likely to encounter difficulties in obtaining workable quantities of peptide. Such studies are required for optimization of antimicrobial activity, product stability, mode of delivery and industrial-scale production, and are vital if these peptides are ever to be brought to the market. Recombinant expression of AMPs is one hope for producing suitable amounts of diverse peptides. Here we review the literature regarding microbial heterologous expression systems for the production of recombinant AMPs.

Lessons from an estivating frog: sparing muscle protein despite starvation and disuse.

Long (6- to 9-mo) bouts of estivation in green-striped burrowing frogs lead to 28% atrophy of cruralis oxidative fibers (P < 0.05) and some impairment of in vitro gastrocnemius endurance (P < 0.05) but no significant deficit in maximal twitch force production. These data suggest the preferential atrophy of oxidative fibers at a rate slower than, but comparable to, laboratory disuse models. We tested the hypothesis that the frog limits atrophy by modulating oxidative stress. We assayed various proteins at the transcript level and verified these results for antioxidant enzymes at the biochemical level. Transcript data for NADH ubiquinone oxidoreductase subunit 1 (71% downregulated, P < 0.05) and ATP synthase (67% downregulated, P < 0.05) are consistent with mitochondrial quiescence and reduced oxidant production. Meanwhile, uncoupling protein type 2 transcription (P = 0.31), which is thought to reduce mitochondrial leakage of reactive oxygen species, was maintained. Total antioxidant defense of water-soluble (22.3 +/- 1.7 and 23.8 +/- 1.5 microM/microg total protein in control and estivator, respectively, P = 0.53) and membrane-bound proteins (31.5 +/- 1.9 and 42.1 +/- 7.3 microM/microg total protein in control and estivator, respectively, P = 0.18) was maintained, equivalent to a bolstering of defense relative to oxygen insult. This probably decelerates muscle atrophy by preventing accumulation of oxidative damage in static protein reserves. Transcripts of the mitochondrially encoded antioxidant superoxide dismutase type 2 (67% downregulated, P < 0.05) paralleled mitochondrial activity, whereas nuclear-encoded catalase and glutathione peroxidase were maintained at control values (P = 0.42 and P = 0.231), suggesting a dissonance between mitochondrial and nuclear antioxidant expression. Pyruvate dehydrogenase kinase 4 transcription was fourfold lower in estivators (P = 0.11), implying that, in contrast to mammalian hibernators, this enzyme does not drive the combustion of lipids that helps spare hypometabolic muscle.

Highly conserved alpha-toxin sequences of avian isolates of Clostridium perfringens.

Clostridium perfringens causes necrotic enteritis in chickens, and alpha-toxin has been suggested to be a key virulence determinant. Analysis of the alpha-toxin of 25 chicken-derived C. perfringens strains demonstrated high homology to mammal-derived strains rather than to the only avian-derived C. perfringens alpha-toxin sequence reported previously.