Source: WASHINGTON STATE UNIVERSITY submitted to
AN INTEGRATED APPROACH TO CONTROL OF BOVINE RESPIRATORY DISEASES (NC-1027)
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
NEW
Funding Source
Reporting Frequency
Annual
Accession No.
1011454
Grant No.
(N/A)
Project No.
WNP00782
Proposal No.
(N/A)
Multistate No.
NC-1192
Program Code
(N/A)
Project Start Date
Oct 27, 2016
Project End Date
Sep 30, 2021
Grant Year
(N/A)
Project Director
Neibergs, HO, LO.
Recipient Organization
WASHINGTON STATE UNIVERSITY
240 FRENCH ADMINISTRATION BLDG
PULLMAN,WA 99164-0001
Performing Department
Animal Science
Non Technical Summary
Bovine Respiratory Disease causes over one million cattle deaths and is estimated to cost the feedlot industry alone over one billion dollars each year. Although vaccines and management practicesdecrease the number of cattle affected with the disease, the number of cattle that will become ill and die of the disease has not changed in the past 20 years. The objective of this study is to identify cattle that are less likely to become ill when exposed to BRD pathogens because of superior genetics. These cattle can be identified when regions of chromosomes that are responsible for increased resistance to BRD are known and selected for. This study aims to discover these chromosomal regions in beef and dairy cattle and provide tools to the dairy and cattle industries to exploit this information to reduce the incidence of BRD through genetic selection. This approach would reduce the reliance on antibiotic (anti-microbial) use for sick cattle, increase food security, improve animal well-being, and improve profitability and sustainability of the beef and dairy cattle industries.
Animal Health Component
100%
Research Effort Categories
Basic
80%
Applied
20%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3033310108050%
3033410108050%
Goals / Objectives
To elucidate pathways by which host characteristics, pathogen virulence mechanisms, and environmental impacts interact to produce BRD, and to develop strategies to mitigate detrimental factors and enhance protective mechanisms.
Project Methods
Genome wide association analysis will be conducted using EIGENSTRAT for 2700 dairy calves and 2000 beef feedlot cattle using the Illumina BovineHD BeadChip which contains 778,000 SNPs. Gene set enrichment analysis and pathway analysis will also be conducted on both the dairy and beef cattle populations. These data will be compared to the genes differentially expressed in weaned beef cattle challenged with one of 7 BRD pathogens whose tissues underwent RNA sequencing.

Progress 10/01/19 to 09/30/20

Outputs
Target Audience:Veterinarians, cattle feeders, dairyman, cow-calf producers, allied health professionals, research scientists. Changes/Problems:As was previously stated, the covid-19 pandemic has left the dairy we were collecting samples from in Wisconsin with too few personnel to continue with the study. We are actively seeking other alternatives for sample collection. What opportunities for training and professional development has the project provided?A new PhD student has joined the program to study the genetics of disease resistance/susceptibility which will include BRD. The undergraduate students reached by the lectures on BRD have exceeded 300 students. How have the results been disseminated to communities of interest?Undergraduate students in animal science, veterinary science, the honors college and agricultural food systems. Veterinarians, animal scientists and researchers through journal articles. Drovers published an article that reviewed my presentation on the genomics of BRD in late 2019 which reaches dairy professionals and producers throughout the U.S. What do you plan to do during the next reporting period to accomplish the goals?We hope to locate a new dairy that we can conduct sampling at that is less affected by the covid-19 pandemic and proceed with our experiment. We are also writing a manuscript for submission on the role of corona virus on BRD in cattle.

Impacts
What was accomplished under these goals? A USDA-NIFA funded proposal (PD Seabury and Co-PD Neibergs) was continued (and then interrupted due to covid) to identify pathogen profiles and loci associated with enhanced resistance to BRD in 1000 pre-weaned calves in Wisconsin. Samples on approximately 150 calves were collected prior to cessation of sample collection due to a decrease in cases, and lack of personnel on the dairy.Bacteriology and virology will be used to identify pathogen profiles from mid-nasal and deep pharyngeal swabs and Illumina BovineHD BeadChips will be used for genotyping. Genome-wide association results will be compared with previous results in pre-weaned dairy calves in California and New Mexico. As the dairy is still under siege on keeping sufficientpersonnel to be able conduct the sampling, we are also trying to locate alternatives to the dairy in Wisconsin to continue with the study.

Publications

  • Type: Journal Articles Status: Published Year Published: 2020 Citation: R.H. Nissly, N. Zaman, P.A.S. Ibrahim, K. McDaniel, L. Lim, J.N. Kiser, I. Bird, S.K. Chothe, G.L. Bhushan, K. Vandegrift, H.L. Neibergs, S.V. Kuchipudi. Influenza C and D viral load in cattle correlates with bovine respiratory disease (BRD): Emerging role of orthomyxoviruses in the pathogenesis of BRD. 2020. Virology 551(December) 10 https://doi.org/10.1016/j.virol.2020.08.014
  • Type: Journal Articles Status: Awaiting Publication Year Published: 2020 Citation: H.L. Neibergs. Genomics: Host Genotype and Relevance to BRD. Animal Health Research Reviews (in press)


Progress 10/01/18 to 09/30/19

Outputs
Target Audience:veterinarians, cattle feeders, dairyman, cow-calf producers, allied health professionals, research scientists Changes/Problems:Sampling of calves has been slower than anticipated due to a tornado that hit the ranch which disrupted animal sampling, and that fewer calves than usual are getting sick. We actually began sampling earlier than anticipated, but have now decided to wait until spring when more calves experience disease to continue sampling. What opportunities for training and professional development has the project provided?Results have been provided at two scientific meetings (Midwest Section American Society of Animal Science, and Bovine Respiratory Disease Symposium as part of the Academy of Veterinary Consultants annual meeting) and in the following college courses: Beef Production, Dairy Production, Honors Research, Agricultural Animal Health and Biology. In addition, graduate and undergraduate students have been involved in this project. How have the results been disseminated to communities of interest?See above What do you plan to do during the next reporting period to accomplish the goals?Continue with the funded proposal to genotype 1000 preweaned calves and conduct genomic analyses to validate loci and identify causal mutations for genomic selection.

Impacts
What was accomplished under these goals? A USDA-NIFA funded proposal (PD Seabury and Co-PD Neibergs) was initiated to identify pathogen profiles and loci associated with enhanced resistance to BRD in 1000 pre-weaned calves in Wisconsin. Bacteriology and virology will be used to identify pathogen profiles from mid-nasal and deep pharyngeal swabs and Illumina BovineHD BeadChips will be used for genotyping. Genome-wide association results will be compared with previous results in pre-weaned dairy calves in California and New Mexico.

Publications

  • Type: Journal Articles Status: Published Year Published: 2019 Citation: 2. J.N. Kiser, M.A. Cornmesser, R. Blackburn, S.M. McGuirk, J.F. Taylor, C.M. Seabury, J.E. Womack, the Bovine Respiratory Disease Complex Coordinated Agricultural Project Research Team, H.L. Neibergs. Validated loci associated with bovine respiratory disease complex in pre-weaned Holstein calves. Animal Genetics https://doi.org/10.1111/age.12878
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: 4. J.L. Hoff, J.E. Decker, R.D. Schnabel, C.M. Seabury, H.L. Neibergs, J.F. Taylor. 2019. QTL-mapping and genomic prediction for bovine respiratory disease in U.S. Holsteins using sequence imputation and feature selection. BMC Genomics 20:555 https://doi.org/10.1186/s12864-019-5941-5
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: 8. M. Neupane, J.N. Kiser, the Bovine Respiratory Disease Complex Coordinated Agricultural Project Research Team, H.L. Neibergs. 2018. Gene set enrichment analysis of SNP data (GSEA-SNP) in dairy and beef cattle with bovine respiratory disease. Animal Genetics http://dx.doi.org/10.1111/age.12718
  • Type: Conference Papers and Presentations Status: Submitted Year Published: 2020 Citation: H.L. Neibergs. 2019. Genomics: Host Genotype and Relevance to BRD. Animal Health Research Reviews.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2018 Citation: H.L. Neibergs, J.N. Kiser, M. Neupane, C.M. Seabury, J.F. Taylor, M.A. Cornmesser, S. McGuirk, R. Blackburn, BRD Consortium, J.E. Womack. 2018. Genome-wide association analysis identifies QTL associated with clinical and sub-clinical bovine respiratory disease. Midwest Section American Society of Animal Science, Omaha, Nebraska.


Progress 10/01/17 to 09/30/18

Outputs
Target Audience:Cattle producers, scientists, veterinarians, allied health care professionals. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?A graduate student used this as partial completion for his PhD dissertation. How have the results been disseminated to communities of interest?Published in a journal and work was also presented at a regional (midwest section) American Society of Animal Sciene meeting and at the Washington State Cattlemen's Association meeting. What do you plan to do during the next reporting period to accomplish the goals?We hope to secure funding to expand our studies to a new population in the midwest.

Impacts
What was accomplished under these goals? An Igenuity Pathway Analysis and Gene Set Enrichment Analysis was conducted to identify gene sets, leading edge genes and upstream regulators associated with BRD in pre-weaned dairy calves and beef feedlot cattle. Holstein calves were sampled from commercial calf raising facilities in California (1003 cases and 1011 controls) and New Mexico (376 cases and 372 controls). Commercial feedlot cattle were sampled from Colorado (500 cases and 499 controls) and Washington (504 cases and 497 controls). There were 102 and 237 unique leading edge genes identified in the dairy calf and beef cattle populations respectively. Six leading?edge genes (ADIPOQ, HTR2A, MIF, PDE6G, PRDX3 and SNCA) were associated with BRD in both dairy and beef cattle. Network analysis identified glucose as the most influential upstream regulator in dairy cattle, whereas in beef cattle, TNF was the most influential upstream regulator. The genes, gene sets and upstream regulators associated with BRD have common functions associated with immunity, inflammation and pulmonary disease and provide insights into the mechanisms that are critical to BRD susceptibility in cattle.

Publications

  • Type: Journal Articles Status: Published Year Published: 2018 Citation: M. Neupane, J.N. Kiser, the Bovine Respiratory Disease Complex Coordinated Agricultural Project Research Team, H.L. Neibergs. 2018. Gene set enrichment analysis of SNP data (GSEA-SNP) in dairy and beef cattle with bovine respiratory disease. Animal Genetics http://dx.doi.org/10.1111/age.12718


Progress 10/27/16 to 09/30/17

Outputs
Target Audience:Target audiences include beef and dairy producers; veterinarians; associated animal health professionals including companies selling vaccines, BRD treatments and genotyping services; dairy and beef breed associations; artificial insemination companies; and schools of higher education where new approaches to reduce BRD are taught. Changes/Problems:The CAP has now been completed so further work will need to be supported by additional funding. What opportunities for training and professional development has the project provided?To date, three post-docs, two graduate students and numerous undergraduates have completed work on this study. How have the results been disseminated to communities of interest?Yes. Two publications have been published and one is submitted. Several presentations (5)have also been given as outlined in "Products" as well as using this information in two courses that I teach. What do you plan to do during the next reporting period to accomplish the goals?There is currently a proposal submitted to further address the goals of this multi-state project.

Impacts
What was accomplished under these goals? Change in Knowledge has resulted from our study. It was not anticipated that the prevalence of pathogens would vary so greatly in different geographic regions in the Western United States in pre-weaned dairy calves. These differences then affected the loci associated with BRD susceptibility in the different locations, as the pathogens responsible for BRD differed. In addition, we have recently validated several loci associated with BRD in dairy calves from a new population in Wisconsin. In beef cattle, pathogen frequency was similar across geographic regions in the Western United States and so the loci associated with susceptibility to BRD were more consistent. The loci identified as associated with susceptibility to BRD are all unique and many are responsible for a good portion of the genetic variation seen in BRD. We have also completed an analysis on subclinical BRD by evaluating lung lesions and this work has been published. This knowledge allows the development of genotyping assays for these loci that can be incorporated into selection indexes that will facilitate the selection of cattle that are less likely to succumb to BRD. Selection for loci that reduce the susceptibility to BRD will result in the decline of the disease, a reduction in the use of antibiotics, added food security, and an improvement in animal well-being.

Publications

  • Type: Journal Articles Status: Published Year Published: 2017 Citation: J.N. Kiser, T.E. Lawrence, M. Neupane, C.M. Seabury, J.F. Taylor, J. E. Womack, the Bovine Respiratory Disease Complex Coordinated Agricultural Project Research Team, H.L. Neibergs. 2017. Rapid Communications: Subclinical bovine respiratory disease  loci and pathogens associated with lung lesions in feedlot cattle. Journal Animal Science 95(3):1080-1091. Doi:10.2527/jas.2016.1152
  • Type: Other Status: Published Year Published: 2017 Citation: Moore, D.A., H.L. Neibergs. 2017. Dairy genomics research update: New aspects of selection for health and fertility Progressive Dairyman August 25, 14:44-45
  • Type: Journal Articles Status: Submitted Year Published: 2017 Citation: J.N. Kiser, M.A. Cornmesser, R. Blackburn, S.M. McGuirk, J.F. Taylor, C.M. Seabury, J.E. Womack, the Bovine Respiratory Disease Complex Coordinated Agricultural Project Research Team, H.L. Neibergs. Validating loci associated with bovine respiratory disease complex in pre-weaned Holstein calves. Animal Genetics