Source: WASHINGTON STATE UNIVERSITY submitted to
GENOMICALLY OPTIMIZED ORGANIC DAIRY (GOOD): GENOME SELECTION AGAINST UTERINE DISEASES TO IMPROVE FERTILITY AND LONGEVITY IN CATTLE
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
NEW
Funding Source
OTHER GRANTS
Reporting Frequency
Annual
Accession No.
1029005
Grant No.
2022-51300-38058
Project No.
WNP00899
Proposal No.
2022-04085
Multistate No.
(N/A)
Program Code
113.A
Project Start Date
Sep 1, 2022
Project End Date
Aug 31, 2026
Grant Year
2022
Project Director
Jiang, Z.
Recipient Organization
WASHINGTON STATE UNIVERSITY
240 FRENCH ADMINISTRATION BLDG
PULLMAN,WA 99164-0001
Performing Department
Animal Sciences
Non Technical Summary
The prohibited use of antibiotics on organic dairy cattle challenges farm biosecurity and disease prevention, for example, resulting in high incidence of metritis and endometritis, low fertility and high culling rate. Here we propose to use genomic sciences and biotechnologies to help organic dairies systematically overcome these challenges and thus enhance market competition, technology modernization and operational sustainability. Therefore, it is imperative for us to establish, develop and maintain a nationally and internationally recognized GOOD (genomically optimized organic dairy) program and thus advance, promote and sustain global GOOD systems for generations to come. We will collaborate with thirty organic dairy farms for collection of blood, uterine swabs and endometrial cell samples to measure DNA variants, RNA dynamics and phenotypic variations. A novel genome wide association study approach will be established to examine allele frequency flows at the genome level, gene networks at the transcriptome level, and uterine disease progression at the phenome level. We will reach out to our advisory board members, organic industry advocates and broad communities for advice, help and support to strengthen our organic dairy program at Washington State University. Additionally, we will help the organic dairy farms participating in the project establish their capability in isolation of DNA for genotyping, extraction of RNA for diagnosis of uterine disease and determination of pathogens for cure strategy. We will present our innovation and discoveries at scientific conferences and freely release the laboratory protocols, training procedures and educational programs developed in the proposed research. We believe that our GOOD program represents a unique strategy to help organic dairy production in the United States of America to realize the projection of revenue increase to $18.9 billion annually by the year 2026. Promotion of organic dairy and organic animal production will benefit the environment, animal well-being and human health. Our GOOD program will prepare next generation scientists and technical personnel to move organic dairy farming to the next level.
Animal Health Component
100%
Research Effort Categories
Basic
50%
Applied
25%
Developmental
25%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
30434991080100%
Knowledge Area
304 - Animal Genome;

Subject Of Investigation
3499 - Dairy cattle, general/other;

Field Of Science
1080 - Genetics;
Goals / Objectives
Many American consumers perceive that organic products are friendlier to the environment, animal well-being and human health. The prohibited use of antibiotics on cattle, however, challenges farm biosecurity and disease prevention. For example, lack of antibiotic treatments makes clinical endometritis and puerperal metritis among the most prevalent reproductive disorders in organic dairies. The overall goal of this project is, therefore, to develop a GOOD (genomically optimized organic dairy) program and use genome sciences and biotechnology to overcome these challenges. Briefly, our GOOD initiative is based on a new USDA blueprint for Animal Genome Research - "Genome to phenome (G2P): improving animal health, production and well-being."Specific Objective #1: Develop a G2P bridge mapping approach as our research core to advance the GOOD program. We will integrate DNA/RNA variants and performance variation information into a multi-omics pipeline and develop a G2P bridge mapping method to identify cows that are resistant to reproductive diseases, such as metritis and endometritis.Specific Objective #2: Develop a G2P focused education/extension program as our dissemination core to promote the GOOD program. We will add G2P sciences to the current organic programs for improved education and extension, thus adding tools and educating the next generation of dairy farmers to advance organic dairies world-wide using novel knowledge and technology.Overall, we will use various platforms to disseminate our GOOD progress as quickly as possible. Locally, we will call advisory board members, stakeholders and students to work together on development of training programs and presentation materials. Regionally, we will support organic dairies and train them to use genomic tools for maximized herd efficiency. Nationally, we will organize annual workshops to promote our GOOD program. Globally, we will hold a GOOD conference to disseminate our results worldwide.
Project Methods
For Specific Objective 1, we will collaborate with Aurora Organic Dairy and Clover Sonoma to develop our G2P bridge mapping approach. As both companies own a total of 30 organic dairy farms, we will be able to collect samples from small-, medium- and large-scale organic dairies. In particular, all these companies possess Jerseys, Holsteins and their crossbreds. For phenome information, we will collect physiological, pathological, reproductive and productive phenotypes. Transcriptome profiling will involve endometrial cells for construction of whole transcriptome termini site sequencing libraries to capture alternative polyadenylation events. The blood samples collected from cows will be shipped to the Neogen Genomics (GeneSeek) service laboratory for DNA exaction and then 1x Bovine SkimSeek sequencing. With these datasets, we will compare two methods: G2P bridgeless and bridge mapping of quantitative traits loci for both metritis or endometritis subjective scores. No doubt, our findings will be important to all organic and potentially conventional dairy systems. Therefore, we will seek help and support from the Council on Dairy Cattle Breeding (CDCB, https://www.uscdcb.com/). Hopefully our G2P assay would be integrated in their genetic and genomic evaluation programs.For Specific Objective 2, We will establish a university-industry partnership model to jointly develop an applied G2P concept with a "knowledge-in/technology-out" strategy for mutual benefits. Our industry team will bring a broad phenome program from farms to the classrooms by 1) giving guest lectures in classes to expose our students to the strengths and challenges of organic dairies in comparison to conventional production and 2) guiding our undergraduate research in developing research priorities and strategies to address emerging phenotypic issues facing organic dairies. On the other hand, our university team will transfer transcriptome and genome techniques from laboratory to farms to monitor uterine disease severity and use genotypes for selection of cows resistant to metritis and endometritis. At the end, advisory board members, industry personnel and university researchers will work together to organize workshops, symposiums or seminars to disseminate information to organic dairy producers; edit a special issue in a scientific journal and present our results at various conferences to further promote our GOOD program.Efforts. We will provide students in either classes or clubs with hands-on training and experiential opportunities in the organic dairy industry, collecting phenotypic traits data and allowing them to learn about real-world scenarios to solve complex situations with emphasis on organic animal and veterinary medicine production. We will present our work in the seminar series in the Animal Sciences Department and at the Center for Reproductive Biology. We will use different social media to disseminate our work to a broad audience. In addition, we will organize workshops on the GOOD program. We may also edit special issues in peer-reviewed journals.Evaluation. For genome variants, each will have a unique ID number, chromosome, genome coordinates, wild type allele sequence(s) (based on the reference genome), mutated allele sequence(s), gene symbol, gene biotypes (at least five types), genome region classification, variant types (single nucleotide polymorphism or insertion/deletions), allele frequencies per locus and genotype per individual. For APA events, each site will have a unique ID number, chromosome, sense/antisense strand, genome coordinates, gene symbol, gene biotypes, transcript ID, genome locations, 3'-end genomic features, polyA signals and the raw/normalized counts for each sample. For trait information, we will estimate repeatability among different times and test time points to improve accuracy.For the student-centered learning outcomes, we will evaluate if participating students will be able to: 1) identify and discuss in a meaningful way issues related to organic dairy production systems; 2) describe and integrate different concepts (e.g., nutrition, reproduction, genetics, personnel, etc.) relevant to the organic production system; 3) critically assess the dairy production systems using records to promote and improve the overall performance and profitability of the farm without neglecting animal welfare and the environment; 4) engage in problem solving using a teamwork approach with stakeholders, dairy farmers, professionals, workers, and managers and 5) potentially identify job opportunities to develop a technical or professional career within the dairy industry.

Progress 09/01/22 to 08/31/23

Outputs
Target Audience:Genome research, education and service community; Animal breeding and genetics companies; Organic and conventional dairy producers, processors and retailers; Veterinarians. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?The award has provided training opportunities for one PhD student, one visiting PhD student, one Master's degree student and three undergraduate students. The training includes laboratory safety, animal care and use, RNA extraction, APA profiling library construction, data analysis and SOP training, for example. How have the results been disseminated to communities of interest?Results have been regularly disseminated to the US bovine FAANG group members, WSU Animal Biology and Biomedicine group members and graduate and undergraduate students who take the Perspectives in Biotechnology class at Washington State University. The information was also shared with broad international communities through a selected talk at the Ruminant Genetics Workshop, 39th International Society for Animal Genetics Conference, Cape Town, South Africa and an invited talk at the Central Dogma of Phenomics Workshop, the American Society of Animal Science Annual meeting 2023, Albuquerque, NM. What do you plan to do during the next reporting period to accomplish the goals?We have a plan to collect samples from Aurora Organic Dairy in Colorado and Clover Sonoma in California and accumulate our datasets in genome, transcriptome, metabolome, microbiome and phenome. We will continue fine-tuning of new statistical models and novel pipelines for data analyses. We will develop cost-effective tools for our industry partners to pursue diagnosis of both metritis and endometritis on farm. We will organize a symposium on organic dairy and facilitate knowledge and technology transfer from research to application.

Impacts
What was accomplished under these goals? We started this funded research project by completing a preliminary study. We have strong evidence to show that alternative polyadenylation (APA) profiles can be used to generate an endometritis progression panel for exploring the bridges between genome and the disease. Especially, pathogens force the host to execute more up-regulated APA sites. In comparison to healthy cows, unhealthy cows tend to use more intronic, but less distal APA sites. Four genes: CD59 molecule, Fc fragment of IgG receptor IIa, lymphocyte antigen 75 and plasminogen may serve as initial contacts or combats with pathogens on cell surfaces, followed by activation of nuclear receptor subfamily 1 group H member 4 to regulate AXL receptor tyrosine kinase, FGR proto-oncogene, Src family tyrosine kinase, HCK proto-oncogene, Src family tyrosine kinase and integrin subunit beta 2 for anti-inflammation. In addition, we also observed that microRNA genes: MIR21 and MIR30A might be a good pair of antagonistic biomarkers for diagnosis of either inflammation or anti-inflammation in the uterus. During this transition stage from a small-scale study to large-scale research, we focused on development of our protocols, procedures and processes before heading to farms for sampling. Specifically, it is our priority to efficiently use samples collected from each animal and thus maximize data collection in genome, transcriptome and phenome to develop the bridge maps for both metritis and endometritis in organic cows. For each cow, we will have pedigree information, production records and reproduction performance plus ultrasonic measurements collected as phenome. Blood samples will be used to produce metabolome and genome datasets, while uterine samples are expected to have both microbiome and transcriptome profiles. The standard operation procedures (SOPs) have been drafted for collection of these datasets for the funded project. In fact, we have been designing a database to include all of these datasets plus sample management systems, including sample storage location, sample processing method and sample analyses results. We started to look at potential challenges associated with big data analysis. Currently, we use the principal component analysis (PCA) to build a disease progression panel. For our funded project, we will collect materials from 1,000 cows. As such, we see potential challenges to pursue PCA analysis on such a large dataset. Instead, we are exploring novel statistical models based on phylogenetic tree construction to overcome the challenge. A key component of transcriptome analysis is to enrich functional pathways. However, understanding the relationships among hundreds or thousands of pathways remains a challenging task. We are developing clustering approaches to make pathway classifications more meaningful to our funded research. In order to apply APA profiles in diagnosis of metritis and endometritis, we are looking into simplified approaches to do so and save costs for organic industries. Using our Department's newsletter, we have released our funded project information to the public as one of our outreach activities. Basically, our GOOD (genomically optimized organic dairy) project will engage an advisory panel of scientists, industry partners and organic dairy producers to understand gene networks underlying uterine disease and thus develop novel tools to identify cows that are resistant to both metritis and endometritis for genetic improvement. No doubt, we have been closely working with our project partners - Aurora Organic Dairy in Colorado and Clover Sonoma in California to develop protocols, procedures and processes for collection of genome, metabolome, microbiome, transcriptome and phenome datasets. We are ready now to start the large-scale sampling process.

Publications

  • Type: Journal Articles Status: Published Year Published: 2023 Citation: Stotts MJ, Zhang YZ, Zhang SW, Michal JJ, Velez JS, Hans B, Maquivar M, Jiang Z. 2023. Alternative polyadenylation events in epithelial cells sense endometritis progression in dairy cows. J. Integr. Agric. 2023;22(6):18201832.
  • Type: Journal Articles Status: Published Year Published: 2023 Citation: Wu XL, Ding X, Zhao Y, Miles AM, Brito LF, Heringstad B, Zhao S, Jiang Z. Editorial: Lactation genomics and phenomics in farm animals: Where are we at? Front Genet. 2023;14:1173595.
  • Type: Journal Articles Status: Published Year Published: 2023 Citation: Carrion SA, Michal JJ, Jiang Z. Alternative Transcripts diversify Genome Function for Phenome Relevance to Health and Diseases. Genes. 2023;14(11):2051.
  • Type: Journal Articles Status: Published Year Published: 2023 Citation: Carrion SA, Michal JJ, Jiang Z. Imprinted genes, genomics conservation, transcriptomic dynamics and phenomic significance in health and diseases. Int J Biol Sci. 2023;19(10):3128-3142.
  • Type: Journal Articles Status: Published Year Published: 2023 Citation: Mikec `, Horvat S, Wang H, Michal J, Kunej T, Jiang Z. Differential alternative polyadenylation response to high-fat diet between polygenic obese and healthy lean mice. Biochem Biophys Res Commun. 2023;666:83-91.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2023 Citation: Jiang Z. Invited Seminar. Genome Science and Healthy Longevity. Annual Advanced Science Seminar Series, Rugao Health Council. 04/18/2023. Rugao City, China.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2023 Citation: Jiang Z. Invited Seminar. The Central Dogma of Phenomics. College of Animal Sciences and Biotechnology, Nanjing Agricultural University. 04/23/2023. Nanjing, China.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2023 Citation: Jiang Z. Selected Speaker. Functional Mapping of Alternative Polyadenylation in Cattle. Ruminant Genetics and Genomics Workshop, 39th International Society for Animal Genetics Conference. Cape Town, South Africa. July 2-7, 2023.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2023 Citation: Jiang Z. Invited Seminar. Central dogma of phenomics: P = G + R + E + G x R x E? Workshop on the central dogma of phenomics. 2023 American Society of Animal Science Annual Meeting. July 16  July 20, 2023. Albuquerque, NM, USA
  • Type: Conference Papers and Presentations Status: Accepted Year Published: 2023 Citation: Jiang Z. Invited Plenary Speaker. Research Frontiers in Animal Phenomics. International Conference on Genetics and Genomics Research Fronts in Animals and Poultry, December 9  10, 2023. Shandong Agricultural University, China
  • Type: Other Status: Published Year Published: 2023 Citation: Michal JJ. GOOD: Genetically optimized organic dairy. Animal Sciences Department News Letter. https://ansci.wsu.edu/2023/05/04/good-genetically-optimized-organic-dairy/
  • Type: Other Status: Published Year Published: 2023 Citation: Zaragoza A. Genomic selection for resistance of metritis in dairy cattle to effectively increase reproductive performance in organic dairy farms. Animal Sciences Department Seminar Series. Fall 2023.