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ARS Home » Plains Area » Clay Center, Nebraska » U.S. Meat Animal Research Center » Genetics and Animal Breeding » Research » Research Project #433992

Research Project: Developing a Systems Biology Approach to Enhance Efficiency and Sustainability of Beef and Lamb Production

Location: Genetics and Animal Breeding

2018 Annual Report

Objective 1: Improve genomic tools for beef cattle and sheep. Sub-objective 1A: Complete improved reference assemblies for beef cattle and sheep using genome-wide and locus-targeted approaches, in addition to comparative approaches, to improve accuracy and contiguity. Sub-objective 1B: Improve annotation of the reference assemblies by conducting specific assays as outlined in the FAANG consortium guidelines, enhanced with parent-of-origin allele expression pattern data. Sub-objective 1C: Develop comprehensive databases of existing variation with predicted impact of those variations on gene expression and protein sequence. Objective 2: Develop systems to improve performance through combined genetic and genomic approaches. Sub-objective 2A: Improve breeding and management decisions by characterizing current genetic and phenotypic variation within and between predominant beef breeds and crosses. Sub-objective 2B: Identification of genomic variation associated with industry-relevant phenotypes in beef cattle. Sub-objective 2C: Development of low-input production lines of sheep, including genetic and genomic resource development to support characterization of these lines. Objective 3: Identify and characterize microbes, microbial populations, and parasites associated with normal and diseased populations. Sub-objective 3A: Profile microbial populations in the respiratory tract (RT) of cattle throughout the production life-cycle in the context of BRDC. Sub-objective 3B: Characterize genomic variation among sheep parasites, for correlation with anthelmintic resistance and animal genotype. Objective 4: Combine products from Objectives 1, 2, and 3 to synthesize a broader knowledge base. Sub-objective 4A: Synthesize genome annotation from Objective 1 and genetics by selection and assessment of impact of predicted non-functional alleles. Sub-objective 4B: Synthesize parasite and metagenomics from Objective 3 with genetics and genomics from Objective 2. Sub-objective 4C: Synthesize variant genotypes and annotation from Objective 1, animal phenotypes from Objective 2, and microbial profiles from Objective 3, by partitioning microbial variation into host genetic and enviromental influences on phenotypic expression.

Challenges to sustainability of beef and lamb production include aspects of animal health and wellbeing, societal expectations of reduced antibiotic use and/or development of alternatives, and pressure to reduce environmental impact of production. Advances in genomic and related technologies have opened new avenues to better understand the relationships between variants of animal genomes, production traits, and the microbes that are associated with animal production. The technologies support and depend on development of research populations with pertinent phenotypes that broadly sample industry genetics, continuing improvement in annotation of animal genomes, identification and characterization of microbial species relevant to animal production, and continued assessment of the interaction of genome variation and production phenotypes. This project plan will merge previous genetics and genomics projects into a broader systems approach, that will encompass (1) genome annotation and identification of functional variation among genomes, (2) development of phenotyped populations in which the effects of variation can be estimated, (3) characterization of the overall microbial diversity associated with the animals and dependencies of this diversity on animal genome variation, and (4) molecular-level characterization of microbial or parasitic organisms that impact on animal health, productivity, and reproduction. The systems approach will be combined with population management strategies, application of advancements in statistical methodology, and partnering with commercial producers. This combination will enable broader understanding of the components contributing to production efficiency, environmental impact, and animal welfare, while developing specific technologies for release to beef cattle producers and improved strains for the sheep industry.

Progress Report
Excellent progress was made on all aspects of the Project Plan, with particularly good results in Objective 1, “improving genomic tools for beef cattle and sheep”, which underlies prospects for success in the other objectives. Specifically, in December 2017 and May 2018, fully annotated replacement reference genome assembly for sheep and cattle (respectively) were made public through the National Center for Biological Information (NCBI). Both the sheep and cattle genome assemblies represent the complete sequence of all autosomes, plus the X sex chromosome (no Y chromosome because the sequenced animals were female). The new cattle reference used the same Hereford breed animal as the previous public reference, but was created with a novel combination of technologies that we pioneered, and is >200-fold improved compared to what was previously available. Note that “annotation” refers to the marking of significant features, primarily genes, on the chromosomes, and the new reference “fixes” many problems with gene annotation from the previous reference plus adds several thousand additional genes and features. Further, we developed an even newer approach to genome assembly that allowed us to use a cross between an Angus breed bull and a Brahman breed cow, and generate separate assemblies for the Angus and Brahman breed parents. In this instance, the animal sequenced was a male fetus, resulting in the most contiguous assembly of a mammalian Y chromosome (for Angus in this cross) ever created by de novo assembly. The Angus and Brahman reference assemblies are even more accurate and complete than the new Hereford reference, and identified genomic features that had been obscured in the older assembly process. We are adapting this improved approach to enhancing the sheep genome reference assembly, by creating a cross between the White Dorper and Romanov sheep breeds, which are the two breeds that are most represented in the Easycare composite breed being developed for release to industry in Objective 2. We anticipate that the new approach will improve upon the existing Rambouillet breed reference assembly we released last year, by >10-fold. Tissues from the new breed cross will be collected Sept. 5, 2018. Additional tools developed included an algorithm to prioritize animals in our cattle population for whole-genome sequencing, to support imputation of sequence to all animals with collected phenotypes. Specifically, the algorithm searches for animals predicted to carry variations that have not previously been well-covered by our previous sequencing. In total, 482 calves have been sequenced sufficiently to project variants with predicted effect on genes annotated on the new Hereford reference, and we are on track to be able to monitor the effects of specific variants on traits. Progress was also strong with respect to our overall goal in all the objectives of developing a Systems Biology approach. Continued matings within the Germplasm Evaluation (GPE) project sampled 18 different sire breeds selected from bulls prominent in the industry and mated to GPE cows via artificial insemination. The total population of GPE cows has reached 3,400 with a target next year of 3,600. The population is already supporting estimation of breed-specific heterosis, an important effect in crossbreeding operations. During FY2018, we released an update to the across-breed Expected Progeny Difference (EPD) adjustment factors, which are a mainstay in the selection of elite genetics for breed associations, as well as commercial and seedstock beef cattle producers. We have collected high-density genotype information on over 15,000 GPE animals that are used in combination with the whole-genome sequencing effort to impute genotype through the entire pedigree, in which we continued monitoring a wide variety of phenotypes including measures of fertility and reproductive success, feed efficiency, and response to vaccination for disease, in addition to more traditional phenotypes related to growth and carcass merit. Phenotype collection included rumen samples for many animals to be analyzed for microbial diversity and content, as part of the broader approach to account for microbial impacts on phenotype. We are well on the path for meeting milestones to incorporate phenotypes of meat tenderness, mature cow weight, cow and steer feed efficiency, and cumulative cow productivity into a more comprehensive profile of EPD factors. We are on target for generating data on the microbial component, having collected nasal swabs from approximately 5,600 calves at key developmental timepoints like preconditioning (140 days old) and weaning (160 days old), and have added other timepoints of prebreeding (70 days old) for approximately 2,100 calves. Significantly, we have sampled 620 calves that exhibited symptoms of respiratory disease, to complement the integration of microbial phenotypes related to feed efficiency and growth, with health-related phenotypes. We have expanded this area of research to encompass viral as well as bacterial microbes, as we identified bovine corona virus as a potentially import pathogen in the USMARC herd. Further, we have explored the use of new techniques for microbial sequencing of animal droppings or rumen contents, to go beyond the standard profiling of ribosomal RNA gene diversity to create reference-quality microbial genome assemblies of microbes and parasites inhabiting/infecting sheep and cattle. In summary, the first eight months of the new Project have kept us on track to reach the ambitious goals set for the 5-year Project Plan.

1. Public release of a new fully annotated, reference genome assembly of Hereford cattle. The bovine genome assembly, whose initial DNA sequence was released in FY2017, was updated to reflect new data on gene content and expression, making the tool ready for use by researchers and industry. All efforts to use genomics to study cattle rely upon the reference genome to accurately represent all the genes and regulatory sequences, in their correct order and orientation. The previous reference genome for cattle had been the Hereford breed assembly produced in 2007 (published in 2009) that was created using outdated technology, and as result had many inaccuracies and deficiencies. ARS researchers at Clay Center, Nebraska, in collaboration with researchers at University of California, Davis; University of Missouri, Columbia; University of Maryland; the National Human Genome Research Institute; the National Center for Biological Information; and ARS researchers in Beltsville, Maryland, released a fully-annotated bovine genome reference assembly of the same animal, using a combination of modern genomic technologies available at Clay Center, Nebraska. The new resource led by BARC, USMARC, and U.C. Davis, is now the globally accepted reference for genomic studies in cattle.

2. Life-cycle productivity of reciprocal crosses produced between Romanov and Rambouillet sheep breeds. ARS researchers at Clay Center, Nebraska, estimated the relative performance of crossbred ewes produced by Romanov sires and Rambouillet dams, compared to crossbred ewes produced by Rambouillet sires and Romanov dams. Mature Romanov ewe’s average about 3.7 lambs born per ewe lambing, whereas Rambouillet average about 1.7 lambs, and this large contrast in litter size was evaluated for the impact on subsequent productivity of crossbred ewe progeny. While there is slight evidence that reciprocal crosses born to Romanov dams have a slight advantage for some reproductive traits, the practical outcome of this evaluation is that performance levels of both types of Romanov crossbred ewes will be similar, allowing the industry to produce the desired crossbred ewes without needing large purebred ewe flocks. Crossbred ewes out of Romanov dams produced a cumulative 9.6 lambs weaned per ewe exposed over five parities compared to 9.4 lambs weaned per ewe exposed from crossbred ewes out of Rambouillet dams. This research shows that productivity and profitability of commercial sheep production could be improved by greater use of Romanov crossbred ewes as the maternal component of terminal crossbreeding systems.

3. Genetic evaluation of beef cattle breed differences in mature weight. With increased selection for faster growth rates in the beef cattle industry, cow mature weight has increased substantially due to a high genetic correlation between mature weight and growth. The increase in mature weight has resulted in reduced production efficiencies due to higher maintenance energy requirements for the national cow herd, and thus higher demand for feed resources. However, heavier cows are not necessarily more productive. By understanding current breed differences for mature weight in prominent beef breeds, breed variation in mature weight can be utilized to reduce feed requirements. Understanding genetic relationships between cow weight and lifetime production can enable appropriate consideration of weight and productivity in selection decisions. ARS researchers, using data from the germplasm evaluation program in Clay Center, Nebraska, estimated differences in mature weight for 18 beef cattle breeds, and estimated correlations between cow weight and cumulative number of calves and calf weight weaned. The range in mature weight differences of 125 lbs will allow producers to adjust breed composition of their herds to reduce feed costs. Conservatively, this difference of 125 lb would translate to 2 lb less feed per day which is a substantial cost savings over the lifetime of the cow. The relationships between cow weight and productivity are weak enough that selection can overcome decreased productivity correlated to increased mature weight. Genetic correlation estimates between cow weight and calves weaned (< -0.33) and cumulative weight weaned (< -0.23) can be incorporated with economic values and correlations among other traits to determine appropriate emphasis for selection on productivity. These differences and correlations are being reported to producers to help them make breeding decisions when choosing sire breeds and sires within breed in commercial cattle production.

Review Publications
Kim, M., Kuehn, L.A., Bono, J.L., Berry, E.D., Kalchayanand, N., Freetly, H.C., Benson, A.K., Wells, J. 2017. The impact of the bovine faecal microbiome on Escherichia coli O157:H7 prevalence and enumeration in naturally infected cattle. Journal of Applied Microbiology. 123:1027-1042.
Marley, K.B., Kuehn, L.A., Keele, J.W., Wileman, B.W., Gonda, M.G. 2018. Genetic variation in humoral response to an Escherichia coli O157:H7 vaccine in beef cattle. PLoS One. 13(5):e0197347.
McDaneld, T.G., Kuehn, L.A., Keele, J.W. 2018. Evaluating the microbiome of two sampling locations in the nasal cavity of cattle with bovine respiratory disease complex (BRDC). Journal of Animal Science. 96:1281-1287.
Thallman, R.M., Kuehn, L.A., Snelling, W.M., Retallick, K.J., Bormann, J.M., Freetly, H.C., Hales, K.E., Bennett, G.L., Weaber, R.L., Moser, D.W., MacNeil, M.D. 2018. Reducing the period of data collection for intake and gain to improve response to selection for feed efficiency in beef cattle. Journal of Animal Science. 96:854–866.
Casas, E., Cai, G., Kuehn, L.A., Register, K.B., McDaneld, T.G., Neill, J.D. 2018. Association of circulating transfer RNA fragments with antibody response to Mycoplasma bovis in beef cattle. BioMed Central (BMC) Veterinary Research. 14:89.
Foote, A.P., Jones, S., Kuehn, L.A. 2017. Association of preweaning and weaning serum cortisol and metabolites with ADG and incidence of respiratory disease in beef cattle. Journal of Animal Science. 95(11):5012-5019.
Schweer, K.R., Kachman, S.D., Kuehn, L.A., Freetly, H.C., Pollak, E.J., Spangler, M.L. 2018. Genome-wide association study for feed efficiency traits using SNP and haplotype models. Journal of Animal Science. 96:2086-2098.
Keel, B.N., Zarek, C.M., Keele, J.W., Kuehn, L.A., Snelling, W.M., Oliver, W.T., Freetly, H.C., Lindholm-Perry, A.K. 2018. RNA-seq meta-analysis identifies genes in skeletal muscle associated with gain and intake across a multi-season study of crossbred beef steers. BMC Genomics. 19:430.
Artegoitia, V.M., Foote, A.P., Tait Jr, R.G., Kuehn, L.A., Lewis, R.M., Wheeler, T.L., Freetly, H.C. 2017. Endocannabinoid concentrations in plasma during the finishing period are associated with feed efficiency and carcass composition of beef cattle. Journal of Animal Science. 95(10):4568-4574.
Paz, H.A., Hales Paxton, K.E., Wells, J., Kuehn, L.A., Freetly, H.C., Berry, E.D., Flythe, M.D., Spangler, M.L., Fernando, S. 2018. Rumen bacterial community structure impacts feed efficiency in beef cattle. Journal of Animal Science. 96(3):1045-1058.
Heaton, M.P., Smith, T.P.L., Freking, B.A., Workman, A.M., Bennett, G.L., Carnahan, J.K., Kalbfleisch, T.S. 2017. Using sheep genomes from diverse U.S. breeds to identify missense variants in genes affecting fecundity. F1000Research. 6:1303.
Schwartz, J.C., Philp, R.L., Bickhart, D.M., Smith, T.P., Hammond, J.A. 2018. The antibody loci of the domestic goat (Capra hircus). Immunogenetics. 70: 317-326. doi:
Workman, A.M., Zhu, L., Keel, B.N., Smith, T.P.L., Jones, C. 2018. The Wnt signaling pathway is differentially expressed during the bovine herpesvirus 1 latency-reactivation cycle: evidence that two protein kinases associated with neuronal survival (Akt3 and bone morphogenetic protein receptor 2) are expressed at higher levels during latency. Journal of Virology. 92:e01937-17. https//
Tait Jr, R.G., Cushman, R.A., McNeel, A.K., Casas, E., Smith, T.P.L., Freetly, H.C., Bennett, G.L. 2018. µ-Calpain (CAPN1), calpastatin (CAST), and growth hormone receptor (GHR) genetic effects on Angus beef heifer performance traits and reproduction. Theriogenology. 113:1-7.
Freking, B.A., King, D.A., Shackelford, S.D., Wheeler, T.L., Smith, T.P.L. 2018. Effects and interactions of myostatin and callipyge mutations: I. Growth and carcass traits. Journal of Animal Science. 96:454–461.
Workman, A.M., Kuehn, L.A., McDaneld, T.G., Clawson, M.L., Chitko-McKown, C.G., Loy, J.D. 2017. Evaluation of the effect of serum antibody abundance against bovine coronavirus on bovine coronavirus shedding and risk of respiratory tract disease in beef calves from birth through the first five weeks in a feedlot. American Journal of Veterinary Research. 78(9):1065-1076.
Keel, B.N., Snelling, W.M. 2018. Comparison of Burrows-Wheeler transform-based mapping algorithms used in high-throughput whole-genome sequencing: application to Illumina data for livestock genomes. Frontiers in Genetics. 9:35.
Ahlberg, C.M., Allwardt, K., Broocks, A., Bruno, K., McPhillips, L., Taylor, A., Krehbiel, C.R., Calvo-Lorenzo, M., Richards, C.J., Place, S.E., Desilva, U., VanOverbeke, D.L., Mateescu, R.G., Kuehn, L.A., Weaber, R.L., Bormann, J.M., Rolf, M.M. 2018. Test duration for water intake, ADG, and DMI in beef cattle. Journal of Animal Science. 96(8):3043-3054.