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).
 
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...