Integrating genomics and transcriptomics to empower dairy breeding for feed efficient animals

Lead Research Organisation: SRUC
Department Name: Research

Abstract

Integrating genomics and transcriptomics to empower dairy breeding for feed efficient animals

Improving feed efficiency (FE) of dairy cattle has been a major interest for animal scientists and dairy farmers over decades. Feed efficiency is a complex trait in dairy cattle and is highly linked to milk yield and methane emission in dairy production. Improving FE of dairy cattle will increase profits of dairy farmers and reduce methane emissions of UK dairy population. Including FE into genetic improvement scheme is one of the top priorities in the UK dairy breeding now.

The overall aim of the proposal is to understand the genetic basis of dairy feed efficiency through integrating population-level phenotypic, genomic, and transcriptomic data, which will be exploited to empower dairy breeding for feed efficient and environmentally-friendly animals. The project builds on SRUC's award-wining Dairy Research Centre (Queen's Anniversary Prize) with 50-year data recording on dairy feed efficiency on a population level. We will apply new methods we recently published on Nature Genetics to this data, to fully utilize and integrate animals' genomic and transcriptomic profiles into understanding genetics of feed efficiency. To achieve the overall aim of the project, we will:
(i) Identify cattle genes and genomic regions that are associated with FE using population-level phenotypic and genomic data;
(ii) Characterize the genes and variants of the cattle genome whose expression is important to FE using genomic and RNA-sequencing information;
(iii) Develop methods and apply the newly acquired genomic and regulatory variants to enhance genomic selection for FE in dairy breeding.

The proposed project builds on SRUC's award-winning Dairy Research Centre with 50-year dairy recording on feed intake, milk production and composition, body weight (BW) and condition, health status, and reproductive events per animal. Three work packages (WP) will be conducted:

(i) WP1: We will generate whole genome-sequencing (WGS) data for 40 representative animals in the study population, plus WGS data we previously sequenced or obtained from publicly-available database. We will use these sequence data to facilitate genotype imputation to obtain sequence-level genotypes in the study population. We will conduct association analyses to identify genes and regions associated with FE using sequence-level genotypes.
(ii) WP2: We will obtain RNA-sequencing for 200 animals in the study population from blood samples. Animals' transcriptomic profiles will be integrated with their genomic data and FE phenotypes to identify regulatory variants associated with FE.
(iii) WP3: We will apply the newly acquired genomic and regulatory variants from WP1 and WP2 into genomic prediction for FE, to develop and assess methods of genomic prediction for FE using the functional variants.

The present project will facilitate improved FE and reduced methane emission in the dairy population, highly relevant to BBSRC's strategic priorities in bioscience for sustainable agriculture and priority areas in data-driven biology. This project has extremely important scientific, economic, and social impact on understanding complex trait of feed efficiency, increasing profits of farmers and dairy industry, and mitigating methane emissions of UK dairy population. The project uses high-quality data and innovative methods to provide the scientific community a role model of integrating population-level omics data into genetic research for complex traits in animals and plants. The research outcome will have great potential to be applied to the UK national genetic improvement programs of dairy cattle. The research outcome will facilitate at least 1% extra genetic progress for UK dairy breeding, worth millions of pounds per year for the UK dairy industry.

Technical Summary

Feed efficiency (FE) is a complex trait in dairy animals and is highly linked to dairy production and Agricultural Net Zero. We recently developed and published pioneering methods to integrate population-level genomic and transcriptomic data for understanding genetics of animal complex traits. Based on a 50-year database on dairy FE, the overall aim of the project is to develop and apply the methods into dissecting the genetic basis of dairy FE through integrating population-level phenotypic, genomic, and transcriptomic data, which can be exploited to empower sustainable dairy breeding for feed efficient animals.
The project builds on SRUC's award-winning Dairy Research Centre with 50-year recording on dairy FE. To achieve the overall aim, three work packages (WP) will be conducted:
(i) WP1: We will generate whole-genome sequencing (WGS) data for representative animals in the study population to facilitate genotype imputation to sequence-level genotypes. We will conduct association analyses to characterize the genomic variants associated with FE using sequence-level genotypes;
(ii) WP2: We will obtain transcriptomic profiles for 200 animals in the study population by RNA-seq of blood samples. Animals' transcriptomic profiles will be integrated with genomic data and FE phenotypes to identify the regulatory variants of the cattle genome that express functional significance to FE;
(iii) WP3: We will apply the acquired genomic and regulatory variants from WP1 and WP2 into genomic prediction for FE.
Research outcome has important scientific, economic, and social impact. The project provides novel knowledge of genomic and regulatory variants underlying FE. The project will facilitate at least 1% extra genetic progress for UK dairy breeding, worth millions of pounds per year for the industry. Research outcome delivers social impact in realizing Agricultural Net Zero and is highly relevant to BBSRC's strategic priorities in bioscience for sustainable agriculture.

Publications

10 25 50
 
Description Advanced training for postdoctoral researcher
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Influenced training of practitioners or researchers
Impact Through the project we are able to train a talented postdoctoral researcher to develop essential knowledge and skills for her scientific excellent and career resilience.
 
Description Advanced training for postgraduate students
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Influenced training of practitioners or researchers
Impact We are able to provide higher-level educational training to the Postgraduate students (MSc student and PhD student) using the methods/pipelines provided from the project.
 
Description Determining potential impacts of Precision Breeding on Animal Welfare
Amount £49,853 (GBP)
Funding ID AW0521 
Organisation Department For Environment, Food And Rural Affairs (DEFRA) 
Sector Public
Country United Kingdom
Start 01/2023 
End 11/2023
 
Description Integrating clinical, data-driven and in-vitro approaches to the study of host-pathogen interactions in bovine digital dermatitis
Amount £208,118 (GBP)
Funding ID BB/X008754/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 06/2023 
End 06/2026
 
Description UKRI Future Leaders Fellows Development Network
Amount £50,000 (GBP)
Organisation United Kingdom Research and Innovation 
Sector Public
Country United Kingdom
Start 03/2023 
End 10/2024
 
Description Understanding molecular variations of cattle genome by machine learning
Amount £600,000 (GBP)
Funding ID 2868882 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 09/2023 
End 10/2027
 
Title Developing FarmGTEx TWAS-server: An Interactive Web Server for Customized TWAS Analysis 
Description Transcriptome-wide association study (TWAS) is an effective method for elucidating the molecular mechanisms underlying the genetic loci associated with complex phenotypes. Due to the complexity of the TWAS analysis pipeline, which includes the construction of the gene expression reference panel, gene expression prediction, and the subsequent association analysis with results from large cohorts of genome-wide association study (GWAS), TWAS analyses remain challenging for genetic studies in many species. We have participated in developing an interactive and user-friendly multispecies TWAS web server, the Farm Animal (Farm) Genotype-Tissue Expression (GTEx) (FarmGTEx) TWAS-server (https://twas.farmgtex.org), to facilitate genetic finding translation across tissues and species. It enables users to conduct gene expression prediction for any individuals with genotypes, GWAS summary statistics imputation, customised TWAS with multiple eQTL models, downstream functional annotations, and result visualization. Additionally, we offer the scientific community 479,203, 1,208, and 657 tissue-gene-trait association trios, representing 1,129 traits in human, 41 traits in cattle, and 11 traits in pig, respectively. The FarmGTEx TWAS-server serves as a comprehensive and user-friendly solution for the scientific community to readily perform the TWAS analysis across tissues and species. The FarmGTEx TWAS-server is an open-access resource freely available at https://twas.farmgtex.org, which will be regularly updated, with the inclusion of more species as the FarmGTEx project expands. 
Type Of Material Improvements to research infrastructure 
Year Produced 2023 
Provided To Others? Yes  
Impact The previous TWAS-servers are mostly developed for human populations and tend to perform less efficient/accurate for animal populations due to different genetic structure. The FarmGTEx TWAS-server we developed is special in that it offers customized TWAS analysis and various downstream functional annotations across multiple tissues and species, e.g., humans, cattle, and pigs. As the FarmGTEx project advances, incorporating more tissues/cell types and more species, will be the further development for the FarmGTEx TWAS-server. The FarmGTEx TWAS-server is a free and interactive platform for the scientific community to explore the genetic mechanism of complex traits and translating genetic results between breeds and species. The case studies we conducted demonstrated that the FarmGTEx TWAS-server effectively maps complex trait genes and translates genetic findings across tissues and species (publication under review). 
URL https://twas.farmgtex.org/
 
Title High-throughput population-level sequencing data for UK cattle 
Description We have generated 240 high-throughput DNA and RNA sequencing data for UK cattle population in early 2024 and we are currently managing the raw data to be generate more reader-friendly data with metadata. We plan to make these data public available as soon as we complete the raw data management. 
Type Of Material Biological samples 
Year Produced 2024 
Provided To Others? No  
Impact We generated population-level whole-genome sequence data and transcriptomic profiles for 120 UK Holstein cattle, which is the largest so far in the UK and provides essential information for the scientific communities studying animal genetics, functional genomics, and animal breeding. 
 
Title Algorithms and pipelines for deciphering genetic regulatory effects across tissues in animal species 
Description We built up algorithms and pipelines for analyzing genetic regulatory effects across tissues in animal species. 
Type Of Material Computer model/algorithm 
Year Produced 2023 
Provided To Others? Yes  
Impact The algorithms and pipelines developed has led to high-impact research publications on Nature Genetics. 
URL https://github.com/FarmGTEx/PigGTEx-Pipeline-v0
 
Description Collaboration with Aarhus University on cattle microbiome research 
Organisation Aarhus University
Country Denmark 
Sector Academic/University 
PI Contribution The method developed from the current BBSRC project was integrated into studies in Aarhus University on dairy cattle microbiome and methane emission.
Collaborator Contribution The partner generated data for the project and conducted part of the data analyses for the project.
Impact Publication under review.
Start Year 2023
 
Description Collaboration with Agricultural and Horticulture Development Board (AHDB) 
Organisation Agricultural and Horticulture Development Board
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution We contribute to method development for genetic improvement for dairy feed efficiency in UK dairy cattle population.
Collaborator Contribution AHDB uses the method we develop in their national evaluation for dairy cattle feed efficiency and they will inform us the performance of the method.
Impact The collaboration contributes to national dairy cattle genomic evaluation for feed efficiency and research publications on genetics of dairy cattle feed efficiency that are under preparation.
Start Year 2023
 
Description Collaboration with University of Edinburgh on lab experiments for cattle feed efficiency 
Organisation University of Edinburgh
Department The Roslin Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution We lead the BBSRC project by generating data, comprehensive data analyses, and result dissemination.
Collaborator Contribution The partner contributed to the wet-lab work associated with sample generation for this project.
Impact We have sent blood samples (from on-farm sampling) to the collaborator in University of Edinburgh for DNA and RNA extraction. The collaborator has successfully conducted DNA/RNA extraction for us for the following project work. Publication under preparation.
Start Year 2023
 
Description Partner of internationally-collaborative FarmGTEx Project (Farm Animal Genotype-Tissue Expression project) 
Organisation Aarhus University
Country Denmark 
Sector Academic/University 
PI Contribution Aarhus University is currently coordinating the Farm Animal Genotype-Tissue Expression Project (FarmGTEx, https://www.farmgtex.org/) to deliver a comprehensive atlas of tissue-specific gene expression and regulation in livestock species through collaborating with over 30 institutions worldwide. (1) The current BBSRC project contributes directly to the global database for cattle genome and transcriptome, representing the core resource from the UK. (2) The current project provides the essential data analyses for the FarmGTEx project for cattle, leading to ongoing publications with the FarmGTEx project. (3) The method developed in the current BBSRC project was applied to FarmGTEx project work in other species (pigs, chicken).
Collaborator Contribution The FarmGTEx project provides efficient bioinformatic pipelines for the transcriptomic analyses (Work Package 2) in this BBSRC project.
Impact https://doi.org/10.1101/2023.02.03.527092 https://doi.org/10.1101/2023.06.27.546670 https://doi.org/10.1101/2023.10.09.561393 https://doi.org/10.1038/s41588-023-01585-7
Start Year 2023
 
Description Industry engagement with Senior Vice President of PEAK Genetics 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact The project had conducted an industry engagement workshop with Dr John Cole, the Senior Vice President of Research and Development for PEAK Genetics (headquartered in Madison, Wisconsin; for cattle genetics and breeding) in 2023. In the workshop we discussed the research methods and output from the current BBSRC project and the potential knowledge transfer of the research output from this project to dairy industry work in PEAK Genetics for cattle breeding.
Year(s) Of Engagement Activity 2023
URL https://peakgenetics.com/
 
Description Press release to general public 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact A press release on the overview and impact of this BBSRC award was published to the general public at the start of the project in 2023. As this project is highly linked to dairy production and agricultural Net Zero, the published press release received wide attention, and inquiries on the project were received from researchers nationally and internationally, from Agriculture and Horticulture Development Board (AHDB) in the UK, and from National Farmers Union Scotland (NFU Scotland). We're preparing for the second press release on disseminating the first research output from the project in mid 2024.
Year(s) Of Engagement Activity 2023,2024
URL https://www.sruc.ac.uk/all-news/breeding-for-feed-efficient-dairy-cows/
 
Description Project Engagement with Agriculture and Horticulture Development Board (AHDB) 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact The AHDB Dairy group visited SRUC Livestock Breeding Team in 2023. We had a full-day presentations and discussion with AHDB on knowledge transfer of research outputs to national genetic improvement programs in AHDB. We had discussed the current BBSRC project in the meetings and decided on the plan for knowledge transfer.
Year(s) Of Engagement Activity 2023
URL https://ahdb.org.uk/dairy
 
Description Project engagement with Farm-GTEx project partners 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact We have regular engagements with the international-collaborative FarmGTEx project (Farm Animal Genotype-Tissue Expression Project) to discuss related project activities and facilitate knowledge exchange. We have introduced the current BBSRC project to the participants of FarmGTEx project through multiple meetings. The researchers in the FarmGTEx project have given us valuable suggestions on data analyses of the project and helped us with dissemination of the project through publications and international conferences.
Year(s) Of Engagement Activity 2023,2024
URL https://www.farmgtex.org/
 
Description Project engagement with general public (LinkedIn) 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact We engaged with a wider audience to introduce the project in 2023 through LinkedIn. The link is given below. This LinkedIn engagement has received wide attention world-wide on this project (12 reposts, plus 87 recommendations) from researchers, industries, and farmers' unions from UK and Ireland, North America, EU, and Asia.
Year(s) Of Engagement Activity 2023
URL https://www.linkedin.com/feed/update/urn:li:activity:7049297231689986048/
 
Description Project engagement with general public (Twitter) 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact We've engaged with the general public to introduce the project in 2023 through Twitter. The link is given below. We received wide attention worldwide on this project (11K views, 28 reposts, 42 recommendations and bookmarks) from this post.
Year(s) Of Engagement Activity 2023
URL https://twitter.com/BingjieLi5/status/1645562542163468291
 
Description Project engagement with the genetic society 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Edinburgh Alliance for Complex Trait Genetics (E-ACTG) meetings are formal meetings sponsored by the UK Genetics Society to disseminate and discuss current hot-topics in genetic research for human, animals, and plants in the UK. I was invited to give a 30-min presentation in this meeting in Edinburgh (Royal College of Physicians of Edinburgh) in 2023 to talk about "A taste of dairy feed efficiency genetics". In the presentation I introduced the overview and work packages of this BBSRC project on "Integrating genomics and transcriptomics to empower dairy breeding for feed efficient animals" which enlightened wide attention and discussion on the project after my presentation.
Year(s) Of Engagement Activity 2023
URL https://genetics.org.uk/events/e-actg-edinburgh-alliance-for-complex-trait-genetics/
 
Description Project industry engagement with ABP Food Group 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact We had a workshop with Declan McDonnell and his colleague from ABP Food Group. The ABP Food Group covers all divisional operations from meat, petfood, renewable fuels & ingredients in the UK, Ireland and worldwide. The workshop aimed to develop R&D collaboration between ABP Food Group (ABP FG) and us in the next 5 years. In the workshop I had introduced our BBSRC project related to dairy feed efficiency and we discussed on potential knowledge transfer of the research output of this project in the next 5 years to food industry.
Year(s) Of Engagement Activity 2024
URL https://abpfoodgroup.com/
 
Description Project industry engagement with Oxford Nanopore Technologies 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact We had a formal meeting with Iain MacLaren-Lee (director of Commercial Development at Oxford Nanopore Technologies Ltd) in February 2024, to discuss the performances of long-read sequencing on genomic analyses that can be potentially integrated into the current BBSRC project. The decision from this meeting was that Oxford Nanopore Technologies will sequence 12 animals for us for free and we provide samples for sequencing. The data generated from Oxford Nanopore Technologies will be transferred to us for research work including the current project work. This activity is expected to start in mid 2024.
Year(s) Of Engagement Activity 2024
URL https://nanoporetech.com/