Source: UNIVERSITY OF MISSOURI submitted to NRP
GENOMICS OF PUBERTY AND FERTILITY IN HEIFERS FOCUSING ON FUNCTIONAL VARIANTS
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
ACTIVE
Funding Source
AFRI COMPETITIVE GRANT
Reporting Frequency
Annual
Accession No.
1022477
Grant No.
2020-67015-31132
Cumulative Award Amt.
$500,000.00
Proposal No.
2019-05314
Multistate No.
(N/A)
Project Start Date
Jun 1, 2020
Project End Date
May 31, 2025
Grant Year
2020
Program Code
[A1211]- Animal Health and Production and Animal Products: Animal Reproduction
Recipient Organization
UNIVERSITY OF MISSOURI
(N/A)
COLUMBIA,MO 65211
Performing Department
Animal Sciences
Non Technical Summary
Fertility is the largest driver of profitability in the economically important beef industry (beef make up 19% of total farm receipts and 40% of livestock receipts) . But, highly accurate tools to select beef females (heifers) that are more fertile have not been available. The overall goal of this project is to identify the genes and DNA markers regulating puberty and fertility in beef heifers to create DNA tests. The project has 4 objectives:1. Estimate amount of variation in measured traits influenced by different genetic effects (additive, dominance, genetic interactions)We will also measure the amount of variation due to genetics shared between traits (genetic correlation)2. Identify DNA markers influencing puberty and fertility from extensive analyses of data from individual breeds3. Combine information across breeds, traits, and data sets to identify gene networks, genes, and variants that influence puberty and fertility4. Focusing on knowledge learned in Objectives 2 & 3, contrast single-trait versus multiple-trait DNA predictions for puberty and fertilityWe expect that we will better understand which genes control differences in puberty and fertility. Beef farmers and ranchers will have new DNA tests to select more fertile heifers, which will increase beef sustainability.
Animal Health Component
33%
Research Effort Categories
Basic
34%
Applied
33%
Developmental
33%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3013310108050%
3033310108125%
3013310102015%
3013310105010%
Knowledge Area
303 - Genetic Improvement of Animals; 301 - Reproductive Performance of Animals;

Subject Of Investigation
3310 - Beef cattle, live animal;

Field Of Science
1081 - Breeding; 1080 - Genetics; 1020 - Physiology; 1050 - Developmental biology;
Goals / Objectives
The long-term goal of our research is to understand genetic influences on reproductive efficiency. The goal of this project is to identify the genes and alleles regulating puberty, fertility, and both traits in beef heifers and to utilize these genetic effects to accurately predict genetic merit for these traits. This will minimize losses due to pre-pubertal and infertile heifers and cows.We will achieve these goals through the following objectives:Estimate variance components (additive, dominance, and epistatic variances along with genetic correlations) for Heifer Pregnancy, Adjusted Days Pregnant, Reproductive Tract Score, Pelvic Width, and Pelvic Height to assess the magnitude of non-additive variance components and to evaluate their use as indicator traits of Heifer Pregnancy in national cattle evaluations.Identify genomic regions and DNA variants influencing puberty and fertility from extensive analyses of data from individual breeds.Combine information across breeds, traits, and datasets to identify gene networks, genes, and variants that influence puberty and fertility.Focus on gene networks, chromosomal regions, and DNA variants identified in Objectives 2 & 3 to contrast univariate versus multivariate genomic predictions for puberty and fertility.
Project Methods
We will use advanced genomic methods to analyze the trait and DNA data collected in this project.We will collect the following traits:Reproductive Tract Scores (a scoring system of puberty status)Pelvic heightPelvic widthDays pregnantThese data will be collected on 2,500 Hereford heifers and 2,500 Red Angus heifers. We will also collect a DNA sample on all 5,000 of these heifers. Heifers will be DNA tested at 50,000 DNA markers. Based on the data at these 50,000 DNA markers, we will be able to infer the genotype at 40 Million DNA markers. These data will add to an existing data set of 6,000 Angus heifer with DNA data and trait records.We will look for associations between DNA markers and variation in the recorded traits. First, we will analyze the relationship between DNA markers and trait variation within a single breed. We will also analyze the data across breeds in the total data set of 11,000 heifers. We will use many methods with different strengths and weaknesses to investigate the data. These methods will look for additive effects and non-additive effects, such as interactions between DNA markers. We will assess if certain networks of genes are over-represented as affecting puberty and fertility. We will also look at the genetic relationships between the traits measured in this project. Finally, we will use the DNA markers and trait records to create DNA predictions of heifer puberty and fertility.

Progress 06/01/23 to 05/31/24

Outputs
Target Audience:During this reporting period, we reached beef producers, veterinarians, breed association staff, and other scientists. Changes/Problems:We hope that challenges have now been addressed and the objectives of the grant will be fully accomplished in this reporting period. What opportunities for training and professional development has the project provided? Nothing Reported How have the results been disseminated to communities of interest?Dr. Decker gave a plenary presentation at the Society for Theriogenology Therio Conference. What do you plan to do during the next reporting period to accomplish the goals?One of the new graduate students will complete GWAS analyses. These will include within-breed analyses of Angus, Red Angus, Hereford and Bos indicus influenced cattle. Additional analyses will also be done to combine data across breeds, including multiple breed GWAS, meta-analyses across breeds, and creating of gene networks. The second graduate student will focus on genomic prediction, including estimation of additive, dominance, and epistatic variances along with genetic correlations for Heifer Pregnancy, Days Open (Adjusted Days Pregnant), Reproductive Tract Score, Pelvic Width, and Pelvic Height. This student will also create single trait and multiple trait genomic predictions of these traits.

Impacts
What was accomplished under these goals? In October of 2023, we genotyped approximately 1,500 Bos indicus-Bos taurus hybrid heifers that were collected from previous research at Deseret Ranches. These are valuable samples to achieve our goals, due to the biological differences in puberty and fertility between Bos indicus and Bos taurus heifers. Bos indicus influenced cattle tend to achieve puberty later and have lower heifer pregnancy rates than Bos taurus heifers. Using these genetic differences, we will be able to identify genes related to delayed puberty and decrease heifer fertility. In early 2024, I recruited a senior research associate and two PhD student to join my group. Having the researchers to complete this project has been a repeated issue. This issue is finally resolved, and we look forward to discovering new biology and genetic prediction insights during the next reporting period.

Publications

  • Type: Journal Articles Status: Published Year Published: 2023 Citation: Arisman, Brian C., Troy N. Rowan, Jordan M. Thomas, Harly J. Durbin, William R. Lamberson, David J. Patterson, and Jared E. Decker. "Evaluation of Zoetis GeneMax Advantage genomic predictions in commercial Bos taurus Angus cattle." Livestock Science 274 (2023): 105266.
  • Type: Journal Articles Status: Published Year Published: 2024 Citation: Durbin, Harly J., Helen Yampara-Iquise, Troy N. Rowan, Robert D. Schnabel, James E. Koltes, Jeremy G. Powell, and Jared E. Decker. "Genomic loci involved in sensing environmental cues and metabolism affect seasonal coat shedding in Bos taurus and Bos indicus cattle." G3: Genes, Genomes, Genetics 14, no. 2 (2024): jkad279.
  • Type: Journal Articles Status: Published Year Published: 2024 Citation: Rowan, Troy N., Robert D. Schnabel, and Jared E. Decker. "Uncovering the architecture of selection in two Bos taurus cattle breeds." Evolutionary Applications 17, no. 2 (2024): e13666.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2023 Citation: Decker, Jared E. "Quantitative Genetics And Population Genomics To Improve Beef Sustainability" Therio Conference, Society for Theriogenology, July 19, 2023, Birmingham, Alabama.


Progress 06/01/22 to 05/31/23

Outputs
Target Audience:During this reporting period, we reached beef producers, veterinarians, breed association staff, and other scientists. Changes/Problems:We continue to struggle to recruit students and scientists to work in my lab. We continue to explore ways to address this issue. In the next period, we will genotype historical samples to increase sample sizes. What opportunities for training and professional development has the project provided?A PhD student supported by the project completed an internship at Angus Genetics Inc. This same student attended the Gordon Research Conference on Quantitative Genetics and Genomics, one of the premier quantitative genetics conferences in the world. Further, there was a Gordon Research Symposium specifically for trainees as part of this meeting. How have the results been disseminated to communities of interest?We had a webinar with the American Hereford Association to discuss the results of this project and opportunities to participate. AJ Knowles gave two presentations to the Angus Genetic Inc and American Angus Association Board of Directors regarding his research during his internship. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? During June, July, and August of 2022, AJ Knowles, a graduate student that Dr. Decker advises and mentors, was an intern at Angus Genetics Inc. (AGI). During his time at AGI, he worked on refining the definition of contemporary groups for their Heifer Pregnancy EPD. In 2024, AGI incorporated these changes into their genetic evaluation. He also worked on a new trait, called First Service Conception. Using contemporary groups in which the heifers were artificially inseminated at least one time, heifers that conceived on their first service were compared to the other heifers in their group. Using the same data set, the accuracy of First Service Conception was nearly double the model accuracy of Heifer Pregnancy. We continued to recruit Hereford heifers to the project.

Publications

  • Type: Journal Articles Status: Published Year Published: 2022 Citation: Smith, Johanna L., Miranda L. Wilson, Sara M. Nilson, Troy N. Rowan, Robert D. Schnabel, Jared E. Decker, and Christopher M. Seabury. "Genome-wide association and genotype by environment interactions for growth traits in US Red Angus cattle." BMC genomics 23, no. 1 (2022): 517.
  • Type: Journal Articles Status: Published Year Published: 2022 Citation: Nilson, Sara M., Barbara Gandolfi, Robert A. Grahn, Jennifer D. Kurushima, Monika J. Lipinski, Ettore Randi, Nashwa E. Waly et al. "Genetics of randomly bred cats support the cradle of cat domestication being in the Near East." Heredity 129, no. 6 (2022): 346-355.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2023 Citation: Decker, Jared E. "The Architecture of Selection in Domesticated Cattle: Hard Sweeps, Soft Sweeps, and Polygenic Selection" Plant and Animal Genome Conference. January 2023.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2023 Citation: Knowles, A.J., Duc Lu, Andre Garcia, Stephen Miller, Kelli Retallick, Jared E. Decker. "Comparisons of Genetic Predictions for Heifer Pregnancy, First Service Pregnancy, and Service Number in American Angus Heifers", Gordon Research Conference on Quantitative Genetics and Genomics, California, February 2023.


Progress 06/01/21 to 05/31/22

Outputs
Target Audience:During this reporting period, we reached beef producers, veterinarians, and breed association staff. Changes/Problems:We continue to struggle to recruit students and scientists to work in my lab. We continue to explore ways to address this issue. Hereford breeders have been slower to enroll heifers in this project, compared with Red Angus breeders. We plan to do some webinars with the American Hereford Association to try and increase this enrollment. If this is not successful, we can genotype historical samples from other breeds. What opportunities for training and professional development has the project provided?A Masters student defended during this reporting period. He was trained in various quantitative genetic skills, including GWAS and genomic prediction. He is going on to a PhD in Biology. How have the results been disseminated to communities of interest?Presentations to several organizations and meetings were given to present this work, including North Central Mini Land-Grant Meeting, International Society for Animal Genetics, AGBT-Ag, Purdue University, and The American Dairy Science Association 42nd Discovery Conference. Blog posts and popular press articles were also used to share these results with lay audiences. What do you plan to do during the next reporting period to accomplish the goals?We will continue to collect Hereford data. We will continue to analyze heifer puberty and fertility data to increase the accuracy of genetic prediction and identify loci and genes associated with variation in those traits.

Impacts
What was accomplished under these goals? We now refer to "Adjusted Days Pregnant" as either "Days to Conception" or "Days Open". Days to Conception is defined as days from the start of the breeding season until the heifer conceives. This means that if a heifer does not conceive, she has a missing observation for Days to Conception. Days Open is the number of days in the breeding season that the heifer was open. If a heifer does not conceive, she get the length of the breeding season as her observation. Using existing industry data from the Red Angus Association of America, we estimated heritibility for Heifer Pregnancy, Days Open, and Days to Conception. Narrow sense heritabilities were similar across all three traits. However, model accuracies and BIF EPD accurcies were higher for Days Open compared to Heifer Pregnancy. So, with exactly the same data set, prediction accuracy increased simply by changing how we define the trait. We also conducted GWAS using this Red Angus data and identified genomic loci influencing fertility in Red Angus. We continued to collect phenotypic and genotypic data from Red Angus and Hereford cattle.

Publications

  • Type: Theses/Dissertations Status: Published Year Published: 2022 Citation: Tuyishimire E. Genomics of heifer pregnancy, days open, and days to conception in Red Angus heifers (Masters Thesis, University of Missouri--Columbia). https://doi.org/10.32469/10355/91538
  • Type: Conference Papers and Presentations Status: Published Year Published: 2021 Citation: Establishing Consistency in Beef Heifer Development Program, National Center for Applied Reproduction and Genomics Webinar Series.
  • Type: Journal Articles Status: Published Year Published: 2021 Citation: Mabry, Makenzie E., Troy N. Rowan, J. Chris Pires, and Jared E. Decker. "Feralization: confronting the complexity of domestication and evolution." Trends in Genetics 37, no. 4 (2021): 302-305.
  • Type: Journal Articles Status: Published Year Published: 2021 Citation: Crum, Tamar E., Robert D. Schnabel, Jared E. Decker, and Jeremy F. Taylor. "Taurine and indicine haplotype representation in advanced generation individuals from three American breeds." Frontiers in Genetics 12 (2021): 758394.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2021 Citation: Decker JE, (2021) Combining Quantitative Genetics and Population Genomics to Improve Beef Sustainability. ISAG 2021, International Society for Animal Genetics, July 26, 2021 (Plenary Presentation)
  • Type: Conference Papers and Presentations Status: Published Year Published: 2021 Citation: Decker JE. (2021) Genotype-by-Environment-by-Management Interactions to Select More Sustainable Cattle. Bair Ranch Lecture, Department of Animal and Range Sciences, Montana State University.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2022 Citation: Decker JE. (2022) Population Genomics of Sustainable Livestock Production. 42nd ADSA Discovery Conference. (Invited Presentation)


Progress 06/01/20 to 05/31/21

Outputs
Target Audience:Druing this reporting period, we reached beef producers, veterinarians, and breed association staff. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Masters student (Esdras Tuyishimire) was trained to execute GWAS and genomic prediction analyses. In July he will attend online Summer Institute in Statistical Genetics hosted by University of Washington. Masters students Emily Smith and Genna Vanwye were trained on the collection of pelvic measurements and reproductive tract score phenotypes. How have the results been disseminated to communities of interest?We have put significant effort into informing stakeholders about the project. We focused on this effort for two reasons. 1) To recruit heifers to the research project. 2) To encourage industry adoption based on our research findings. We have had online webinars, in-person presentations, blog posts, and popular press articles to reach these articles. For example: http://blog.steakgenomics.org/2020/02/HeiferRecruitment.html http://blog.steakgenomics.org/2020/07/heifer-puberty-and-fertility-project.html http://blog.steakgenomics.org/2021/01/the-genetics-of-fertility-existing-and.html https://issuu.com/redangusassociation/docs/201382_red_angus_oct20_complete_lr/40 https://www.beefmagazine.com/beef/new-research-creates-dna-tests-heifer-fertility What do you plan to do during the next reporting period to accomplish the goals?In the next reporting period, we hope to complete heifer recruitment, phenotyping, and genotyping by recruiting approximately 2,000 additional heifers to the project. Once heifer recruitment is complete, we will switch into data analysis. We plan to finish the analysis of the 4,000 genotyped and 18,000 phenotyped heifers from the data owned by the Red Angus Association of America in the spring of 2022 and submit for publication.

Impacts
What was accomplished under these goals? We recruited, collected phenotypes, and genotypes on approximately 3,000 heifers (of the total of 4,850) in year 1 of the project. Phenotypic data was entered into our Show-Me-Select database. DNA samples were inventoried in the Mizzou Animal Genomics database. DNA samples were sent to Neogen GeneSeek for genotyping. Genotypes were retrieved and stored in the Mizzou Animal Genomics database. A copy of the genotypes were sent to the appropriate breed association and collaborating producers received free genomic-enhanced expected progeny differences. We analyzed pregnancy data and genotypes on 4,000 Red Angus heifers from the Red Angus Association of America. A manuscript describing this work will be submitted in 2022. We estimated heritabilities for Heifer Pregnancy and Days Open (how many days in the breeding season was the heifer not pregnant). We also estimated the heritability of Days to Concepiton (how many days until the heifer became pregnant), but this measure is undefined (missing) for heifers that did not become pregnant. We also estimated the genetic correlation between Heifer Pregnancy and Days Open. We looked for DNA variants associated with Heifer Pregnancy, Days Open, Days to Conception. We also looked for DNA variants associated with either Heifer Pregnancy or Days Open in a multivariate model.

Publications

  • Type: Websites Status: Published Year Published: 2021 Citation: A Steak in Genomics. http://blog.steakgenomics.org/
  • Type: Other Status: Published Year Published: 2020 Citation: Decker, JE. The Genetics of Fertility: Existing and Developing Tools. Oklahoma State University Rancher's Lunchtime Series. https://youtu.be/zi-h5-EHpbQ December, 2020.
  • Type: Other Status: Published Year Published: 2021 Citation: Thomas J and Decker JE. Missouri Cattlemen's Association Show-Me-Select Educational Program. January 8th, 2021.