Developing next generation genetic improvement tools from next generation sequencing
Lead Research Organisation:
University of Edinburgh
Department Name: The Roslin Institute
Abstract
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Technical Summary
The UK dairy research and industrial sectors, as well as RCUK, will invest heavily in sequence data in the coming years. This proposal will ensure that the infrastructure and strategy underpinning this investment is optimal. The platform generated will allow for the combination and analysis of both genotype and sequence information on the UK (dairy) cattle population, and will serve as a technology example for other livestock species. There are three components to this proposal. The first will develop a strategy for collecting sequence information across a whole population. The second will put in place the infrastructure required to handle, share, analyse, and utilise inter(national) shared sequence data within the UK dairy breeding and research communities. The third will evaluate the ability of sequence data to increase the accuracy of genomic selection and the power of genome wide association studies in national dairy cattle populations. Through these activities this project will develop the strategy, infrastructure, and expertise for sequence data required by the UK breeding sector and through this will help maintain world class standards in both the science and application of dairy production in the UK.
Planned Impact
The future sustainability of the UK dairy industry relies on farmers being able to respond to key market signals and future developments in genetic improvement tools are likely to be a key. The partners have successfully worked together to deliver R&D that drives the ongoing changes in the genetic and genomic improvement tools used by farmers. For example, SRUC has delivered information on, and produced, practical dairy selection tools, particularly the inclusion of fertility, health, welfare and survival traits. Adoption of new indexes have improved animal health and welfare and economic performance compared to continued use of previous selection practices, and has cumulatively reduced greenhouse gas emissions per breeding animal by 1.4%/yr. The overall annualised economic benefits of the genetic improvement that has taken place in the years 1980-2009 is worth £127 million/year to the UK dairy industry.
Globally and within the UK dairy production is important both commercially and for research. Dairy genetics is particularly important for research because, due to its high commercial value, it serves as a model species for all other livestock. For example, dairy cattle breeding was the first to widely adopt genomic selection and was the sector that undertook many of the innovations in genetic and genomic evaluations.
Sequence data is expensive and therefore requires a unified approach involving all stakeholders. In dairy this includes research organisations, farmers, private companies, levy boards, and research funding agencies. In this proposal we will bring these groups together by developing a unified strategy for the collection, handling, and utilisation of sequence information within the UK dairy industry.
(i) The academic community. Sequence data is of great value for the prediction and understanding of quantitative traits. However, small islands of sequence data are of limited value on their own - to benefit from sequence huge quantities are needed - quantities that are far beyond the scope of a single researcher or a single research project. This proposal will put in place the strategy and infrastructure to generate the quantities of sequence data that is required by current and future researchers.
(ii) Commercial sequence and genotype providers. Companies providing SNP or sequence data will be able to add value to the data that they generate.
(iii) Society. All members of society who work to improve or depend upon the competitiveness and sustainability of agriculture will benefit from the downstream practical applications. The application of the research by breeding organisations will lead to faster and more sustainable genetic progress, leading to healthier food, and food production that is more resource efficient and affordable. Increased efficiencies in agriculture has direct societal benefits in greater food security with less environmental impact.
(iv) UK science base. The proposed research will provide a platform for increased R&D capabilities in the UK, maintaining its scientific reputation and associated institutions, with increased capability for sustainable agricultural production.
(v) Training. The proposed research will be embedded within training courses that the investigators are regularly invited to give, and the post-docs and programmer working on the project will have the opportunity to be trained in world leading livestock genetics community in a cutting edge area of research. Further, this project is aligned to delivery of already awarded projects (involving postdocs and PhD). This cohort of early career researchers will greatly benefit from the activity of the community.
(vi) Funding agencies. Funding agencies will be required to fund sequence data in the coming year. This research will put in place the tools and ideas required to optimise this. investment and to maximise its complementarity to investments from other organisations (e.g. breeding companies).
Globally and within the UK dairy production is important both commercially and for research. Dairy genetics is particularly important for research because, due to its high commercial value, it serves as a model species for all other livestock. For example, dairy cattle breeding was the first to widely adopt genomic selection and was the sector that undertook many of the innovations in genetic and genomic evaluations.
Sequence data is expensive and therefore requires a unified approach involving all stakeholders. In dairy this includes research organisations, farmers, private companies, levy boards, and research funding agencies. In this proposal we will bring these groups together by developing a unified strategy for the collection, handling, and utilisation of sequence information within the UK dairy industry.
(i) The academic community. Sequence data is of great value for the prediction and understanding of quantitative traits. However, small islands of sequence data are of limited value on their own - to benefit from sequence huge quantities are needed - quantities that are far beyond the scope of a single researcher or a single research project. This proposal will put in place the strategy and infrastructure to generate the quantities of sequence data that is required by current and future researchers.
(ii) Commercial sequence and genotype providers. Companies providing SNP or sequence data will be able to add value to the data that they generate.
(iii) Society. All members of society who work to improve or depend upon the competitiveness and sustainability of agriculture will benefit from the downstream practical applications. The application of the research by breeding organisations will lead to faster and more sustainable genetic progress, leading to healthier food, and food production that is more resource efficient and affordable. Increased efficiencies in agriculture has direct societal benefits in greater food security with less environmental impact.
(iv) UK science base. The proposed research will provide a platform for increased R&D capabilities in the UK, maintaining its scientific reputation and associated institutions, with increased capability for sustainable agricultural production.
(v) Training. The proposed research will be embedded within training courses that the investigators are regularly invited to give, and the post-docs and programmer working on the project will have the opportunity to be trained in world leading livestock genetics community in a cutting edge area of research. Further, this project is aligned to delivery of already awarded projects (involving postdocs and PhD). This cohort of early career researchers will greatly benefit from the activity of the community.
(vi) Funding agencies. Funding agencies will be required to fund sequence data in the coming year. This research will put in place the tools and ideas required to optimise this. investment and to maximise its complementarity to investments from other organisations (e.g. breeding companies).
People |
ORCID iD |
John Hickey (Principal Investigator) |
Publications
Antolín R
(2017)
A hybrid method for the imputation of genomic data in livestock populations.
in Genetics, selection, evolution : GSE
Battagin M
(2016)
Effect of manipulating recombination rates on response to selection in livestock breeding programs.
in Genetics, selection, evolution : GSE
Battagin M
(2018)
A family-based phasing algorithm for sequence data
Desire S
(2023)
A genome-wide association study for loin depth and muscle pH in pigs from intensely selected purebred lines.
in Genetics, selection, evolution : GSE
Gaynor R
(2017)
A Two-Part Strategy for Using Genomic Selection to Develop Inbred Lines
in Crop Science
Gonen S
(2017)
Potential of gene drives with genome editing to increase genetic gain in livestock breeding programs.
in Genetics, selection, evolution : GSE
Gonen S
(2017)
The potential of shifting recombination hotspots to increase genetic gain in livestock breeding
in Genetics Selection Evolution
Description | Sequence data is increasingly used in livestock genetics to design breeding strategies aiming to improve the efficiency of herds or crops within land and water constrains. However, the costs of sequence data are a hurdle to biologically informing the best breeding strategies. Therefore we have developed low-cost strategies based on imputation of sequence data by maximising the information extracted using a strategy based on sequencing key individuals. |
Exploitation Route | The AlphaSeqOpt package is freely available in AlphSuite and includes supporting manual, and access to technical support with the aim of benefiting the academic research community in animal breeding, and expect to have the publication accepted in the near future. The availability of AlphaSeqOpt is a key element on the Innovate UK funded projects with livestock breeding companies (15AGRITECHCAT3: BB/N004728/1 and BB/N004736/1) . |
Sectors | Agriculture Food and Drink Digital/Communication/Information Technologies (including Software) Environment |
URL | http://www.alphagenes.roslin.ed.ac.uk/alphasuite-softwares/alphaseqopt/ |
Description | The AlphaSeqOpt package, resulting from this project, is freely available in AlphaSuite and includes supporting manual, and access to technical support with the aim of benefiting the academic research community in animal breeding and human genetics. The availability of AlphaSeqOpt is a key element on the Innovate UK funded projects with livestock breeding companies (15AGRITECHCAT3: BB/N004728/1 and BB/N004736/1). |
First Year Of Impact | 2016 |
Sector | Agriculture, Food and Drink,Digital/Communication/Information Technologies (including Software),Environment |
Impact Types | Economic |
Description | Newton Fund Workshop Brazil |
Amount | £52,000 (GBP) |
Funding ID | 228949780 |
Organisation | British Council |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2016 |
End | 09/2016 |
Description | Newton Fund Workshop Mexico |
Amount | £37,550 (GBP) |
Funding ID | 2016-RLWK7-10399 |
Organisation | British Council |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2017 |
End | 03/2018 |
Description | Continued development of AlphaImpute |
Organisation | Geno Global Ltd. |
Country | Norway |
Sector | Private |
PI Contribution | AlphaImpute is a software package for imputing and phasing genotype data in populations with pedigree information available. The program uses segregation analysis and haplotype library imputation to impute alleles and genotypes. |
Collaborator Contribution | Trygve Solberg Geno investment supports the maintenance and improvement of AlphaImpute by contributing to the salary of a post-doctoral researcher. |
Impact | This collaboration has not produced any outputs to date. |
Start Year | 2016 |
Description | Partnership with Geno Global |
Organisation | Geno Global Ltd. |
Country | Norway |
Sector | Private |
PI Contribution | In this partnership we will work together to develop and implement genotyping, sequencing and imputation strategies and tools in the Norwegian Red population central to Geno Global. The work seeks to integrate AlphaImpute, our imputation software, into the routine breeding value estimation pipeline at Geno. We will also perform analysis of the resulting data to aid the use of genomic prediction methods in the Geno breeding program and to help the discovery of causal variants that segregate in the Norwegian Red population. |
Collaborator Contribution | Geno has provided historical data form their herd and made it available to develop and train new imputation strategies. |
Impact | Developed an imputation strategy with Geno. |
Start Year | 2016 |
Description | Sequencing of beef cattle in Ireland |
Organisation | Illumina Inc. |
Department | Illumina |
Country | United Kingdom |
Sector | Private |
PI Contribution | The objectives of this project is to generate large data set for the Irish beef and cattle market, analyse it and obtain insights into the mechanics of the resulting predictions underlying the biology of the beef and dairy population. The AlphaSuite is a collection of software that we have developed to perform many of the common tasks in animal breeding, plant breeding, and human genetics including genomic prediction, breeding value estimation, variance component estimation, GWAS, imputation, phasing, optimal contributions, simulation, field trial designs, and various data recoding and handling tools. |
Collaborator Contribution | Illumina is providing the DNA sequencing data on more than 1000 cattle. |
Impact | At this stage of the collaboration the outputs have not been generated. |
Start Year | 2016 |
Title | AlphaAssign |
Description | AlphaAssign is a parentage assignment program in genotype data, using a likelihood based model to determine the sire of an individual based on a list of potential sires. Application is in large scale genotyping/resequencing projects in livestock breeding. |
Type Of Technology | Software |
Year Produced | 2019 |
Impact | AlphaAssign has seen adaptation in both the academic and industry communities. It has been used to perform parentage assignment for ecological populations, such as squirrels and vervet monkeys. In the industry community it has been used to perform parentage assignment as part of a pig-breeding program, and was used as the basis of a maternal grand-parent assignment algorithm, AlphaMGS assign |
URL | https://alphagenes.roslin.ed.ac.uk/wp/software-2/alphaassign/ |
Title | AlphaFamImpute |
Description | AlphaFamImpute is a genotype calling, phasing, and imputation software package for large full-sib families in diploid plants and animals which supports individuals genotyped with SNP array or GBS data. |
Type Of Technology | Software |
Year Produced | 2019 |
Impact | The software package is currently used by our industrial partners in crop breeding |
URL | https://alphagenes.roslin.ed.ac.uk/wp/software-2/alphafamimpute/ |
Title | AlphaSeqOpt |
Description | With improving technologies and decreasing costs, it is now possible and much more informative to collect genomic data by whole genome sequencing. However, sequencing all individuals at high coverage in a large population is not feasible. Instead, we can harness the fact that individuals within a population are related and thus share sections of the genome. If we can identify and sequence individuals that share more of their genome with a large number of individuals in the population then we can pass on the generated sequence data to other individuals that share the same regions of the genome as the sequenced individual, a process known as imputation. AlphaSeqOpt is a software tool that enables researchers and breeders to define a minimal set of individuals that share more of their genomes with a large number of individuals in the population. AlphaSeqOpt also provides the sequencing investment required for a key individual in order to generate accurate and high quality sequence data that can be used to impute sequence for other individuals in the population. |
Type Of Technology | Software |
Year Produced | 2016 |
Impact | The AlphaSeqOpt package is freely available in AlphSuite and includes supporting manual, and access to technical support with the aim of benefiting the academic research community in animal breeding, and expect to have the publication accepted in the near future. AlphaSeqOpt is a key element on the Innovate UK funded project with PIC and Innovate UK Aviagen, and ICBF project. |
URL | http://www.alphagenes.roslin.ed.ac.uk/alphasuite-softwares/alphaseqopt/ |
Description | AlphaGenes Twitter channel |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The AlphaGenes updates the scientific community and a broader audience about news around our research group, scientific output and engagement activities |
Year(s) Of Engagement Activity | 2012,2013,2014,2015,2016,2017,2018,2019,2020 |
URL | https://twitter.com/Alpha_Genes |
Description | AlphaGenes website |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The AlphaGenes website informs the scientific community about the groups research activities, outputs, courses and available software tools. |
Year(s) Of Engagement Activity | 2017,2018,2019,2020 |
URL | https://alphagenes.roslin.ed.ac.uk |
Description | Big Data in Agriculture, Part of the DuPont Pioneer Plant Sciences Symposia Series, at Roslin Institute, 14-15 May 2018 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Symposium held at the Roslin institute, organised by members of my group, sponsored by third parties from the breeding industry |
Year(s) Of Engagement Activity | 2018 |
Description | Contribution to the New York Time article: Open Season Is Seen in Gene Editing of Animals |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Open Season Is Seen in Gene Editing of Animals was a feature article on gene Editing by Amy Harmon. Professor John Hickey was interviewed as specialist in the Quantitative Genetic field. |
Year(s) Of Engagement Activity | 2016 |
URL | https://www.nytimes.com/2015/11/27/us/2015-11-27-us-animal-gene-editing.html?_r=0 |
Description | John Hickey Guest in Farming Today (BBC Radio 4) |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | On Monday 26th September, The BBC Radio 4 Farming Today had Professor John Hickey as specialist scientist on the subject of breeding programs and scientific impact. |
Year(s) Of Engagement Activity | 2016 |
URL | http://www.bbc.co.uk/programmes/b07w5xxq |
Description | Modern plant and animal applied genomics driven by genotype and sequence data, University of Zagreb, Croatia, 17-19 July 2018 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Workshop organised and given by me and two other members of my group. |
Year(s) Of Engagement Activity | 2018 |
Description | Public engagement at the Royal Highland Show |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | All members of the research group engaged the visitors of the RHS, to show the importance of their research towards the enhancement of the agricultural sector in direct or indirect ways. |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.royalhighlandshow.org |
Description | Researcher Links workshop at CNRG, INIFAP, Tepatitlán and Guadalajara, Mexico, 3-7 February 2018 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Workshop organised and given by me and the members of my group |
Year(s) Of Engagement Activity | 2018 |
Description | Short course in Evolutionary Quantitative Genetics |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Study participants or study members |
Results and Impact | Evolutionary Quantitative Genetics course was a comprehensive review of modern concepts in Evolutionary Quantitative Genetics. The contents of the course are basic statistics, population genetics, quantitative genetics, evolutionary response in quantitative traits, estimating the fitness of traits and mixed models and their extensions. the instructor was Dr Bruce Walsh, Department of Ecology Evolutionary Biology, University of Arizona, and co-author of Genetics and Analysis of Quantitative Traits. The Course was hosted by Professor John Hickey at the Roslin Institute. |
Year(s) Of Engagement Activity | 2016 |
URL | http://www.alphagenes.roslin.ed.ac.uk/bruce-walsh-visit/ |
Description | Teaching course: Next Generation Plant and Animal Breeding Programs, Animal Science Department, University of Nebraska, Lincoln. |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Series of the lectures and workshops on Plant and Animal Breeding Programs exploring current practices and future areas of research. The course was designed and imparted by John Hickey and key members of his team. |
Year(s) Of Engagement Activity | 2016 |
URL | http://animalscience.unl.edu/next-generation-plant-and-animal-breeding-programs |
Description | The Expert Working Group on Wheat Breeding Methods and Strategies |
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 | Expert Working Group on Wheat Breeding Methods and Strategies seeks to exchange breeding methods research information and germ plasm to expert build capacity and support in wheat breeding programs, with more efficient breeding methods consistent with the latest scientific advances. The EWG is working on activities such us workshops, training courses, communications, and sharing of germplasm and information to reach larger pool of wheat breeders and trained in state-of-the-art breeding methods. |
Year(s) Of Engagement Activity | 2015,2016,2017 |
URL | http://www.wheatinitiative.org/activities/expert-working-groups/wheat-breeding-methods-and-strategie... |