report of a workshop on “the future of livestock...

1616thth Meeting of the USMeeting of the US--EC Task Force on Biotechnology Research, July 19EC Task Force on Biotechnology Research, July 19--20, 2006 20, 2006

Report of a Workshop onReport of a Workshop on““The Future of Livestock GenomicsThe Future of Livestock Genomics””

1717--18 July 200618 July 2006

Chris Warkup (Genesis Faraday), John Chris Warkup (Genesis Faraday), John Claxton (EC) and Ronnie Green (USDA)Claxton (EC) and Ronnie Green (USDA)

OverviewOverview

Animal BreedingAnimal BreedingWhere genomics fitsWhere genomics fitsThe stateThe state--ofof--thethe--artartConcordance of prioritiesConcordance of prioritiesOpportunities for collaborationOpportunities for collaborationThe way forwardThe way forward

Classical Breeding PyramidClassical Breeding Pyramid

Elite

Multiplier

Commercial

Purebreds‘Pedigree’ breeding

Multiplication ofimproved stock andhybrid production

Crossing of dam and sire

lines

Meat, milk, eggs, wool

Very Significant ProgressVery Significant Progress

6710,0006000Milk/cow/lactation (Kg)Dairy cows8090005000Eggs/tonne feed30300230Eggs per yearLayer hens431.73.0Feed conversion ratio6040100Days to 2 KgBroiler chickens10017085Kg lean meat/tonne feed375540Lean %502114Pigs weaned /sow/yearPigs

% ChangePresent1960sIndicative PerformanceTraitSpecies

Modified from van der Steen, Prall and Plastow, 2005 J. Anim Sci 83: E1-E8

Selective Breeding is a Selective Breeding is a Powerful ToolPowerful Tool

Slide courtesy of Roslin Institute

Sustainability IssuesSustainability Issues

Animal Welfare Animal HealthEnvironmental Footprint

WaterGreenhouse gases and ammoniaOdour nuisanceLandscape

BiodiversityZoonoses

ProfitCost of productionValue of Output

QualityNutritional ValueDistinctivenessSupply & Demand

Global demand for animal products growing steadily

Breeders Now Have More Balanced Breeders Now Have More Balanced Breeding GoalsBreeding Goals

Traditional breeding goalsTraditional breeding goals–– GrowthGrowth–– YieldYield–– EfficiencyEfficiency–– (quality)(quality)

Current breeding goalsCurrent breeding goals–– GrowthGrowth–– YieldYield–– EfficiencyEfficiency–– FitnessFitness–– Fertility Fertility –– Food qualityFood quality–– Food safetyFood safety–– Disease resistanceDisease resistance–– WelfareWelfare–– RobustnessRobustness–– LongevityLongevity–– BehaviourBehaviour–– Managing diversityManaging diversity

Anatomy of the WorkshopAnatomy of the Workshop

StateState--ofof--thethe--artart–– Genome architectureGenome architecture–– Comparative genomicsComparative genomics–– Functional genomicsFunctional genomics–– Dissection of complex traitsDissection of complex traits–– EpigeneticsEpigenetics–– Use of genomic information Use of genomic information

in selectionin selection–– HostHost--pathogen interactionspathogen interactions–– Genetic ModificationGenetic Modification

Society and EthicsSociety and Ethics–– Animal cloning and GM Animal cloning and GM –– a a

prospective studyprospective study–– Views of society on medical Views of society on medical

and and agriagri--food uses of food uses of biotechbiotech

–– Lessons from agronomyLessons from agronomy

The Way Forward The Way Forward

Are Animal Genomics Research Priorities the Are Animal Genomics Research Priorities the Same as for Human Genomics?Same as for Human Genomics?

Many of the research objectives are the Many of the research objectives are the samesame

Francis CollinsFrancis Collins’’2004 Nature Paper2004 Nature Paper

Francis CollinsFrancis Collins’’ Grand Grand ChallengesChallenges

1 Genomics to Biology1 Genomics to BiologyStructural and Functional componentsStructural and Functional componentsOrganisation of networks and how they contribute to Organisation of networks and how they contribute to phenotypesphenotypesA detailed understanding of heritable variationA detailed understanding of heritable variationUnderstand evolutionary variation across speciesUnderstand evolutionary variation across speciesPolicy that facilitates widespread use of genome Policy that facilitates widespread use of genome information information ……

Francis CollinsFrancis Collins’’ Grand Grand ChallengesChallenges

2 Genomics to Health2 Genomics to HealthStrategies for identifying the genetic contributions to Strategies for identifying the genetic contributions to diseasediseaseStrategies to identify gene variants that contribute to good Strategies to identify gene variants that contribute to good healthhealthGenomeGenome--based approaches to prediction of disease based approaches to prediction of disease susceptibility and drug response, early detection of susceptibility and drug response, early detection of illnessillness……Understanding of genes and pathways to develop new Understanding of genes and pathways to develop new therapeutic approaches to diseasetherapeutic approaches to disease……

3 Genomics to Society3 Genomics to Society

Are Animal Genomics Research Priorities the Are Animal Genomics Research Priorities the Same as for Human Genomics?Same as for Human Genomics?

Many of the research objectives are the Many of the research objectives are the samesameThe big differences are:The big differences are:–– Breeders seek to increase the frequency of Breeders seek to increase the frequency of

desirable allelesdesirable alleles–– They need new methods and tools to combine They need new methods and tools to combine

quantitative and molecular genetic approachesquantitative and molecular genetic approaches–– There are different societal questions There are different societal questions

A HighA High--Level View of theLevel View of theStateState--ofof--thethe--ArtArt

Genomes Sequenced:Genomes Sequenced:–– 2004 2004 ChickenChicken–– 2004/052004/05 BovineBovine–– 20062006 Rabbit Rabbit –– 2x scaffolds2x scaffolds–– 20072007 Pig Pig –– at least 4x at least 4x –– 20072007 HorseHorse–– ?? SalmonSalmon–– ?? Sheep Sheep

A HighA High--Level View of theLevel View of theStateState--ofof--thethe--ArtArt

Genomes Sequenced:Genomes Sequenced:–– ‘‘FinishingFinishing’’ of priority speciesof priority species–– Strategies for other speciesStrategies for other species

Other tools and resourcesOther tools and resources–– Curation and annotation of genomesCuration and annotation of genomes–– SNP PanelsSNP Panels

The ones we have are not big enough (for some purposes)The ones we have are not big enough (for some purposes)Some species still donSome species still don’’t have panelst have panelsSome species still need better mapsSome species still need better maps

–– Phenotyped populationsPhenotyped populations

A HighA High--Level View of theLevel View of theStateState--ofof--thethe--Art Art -- 22

Dissecting the Genetics of Complex TraitsDissecting the Genetics of Complex Traits–– QTL to QTN not easyQTL to QTN not easy–– How much variation is structural in origin?How much variation is structural in origin?

Research ToolsResearch Tools–– Functional GenomicsFunctional Genomics–– Comparative GenomicsComparative Genomics

BirdBird--Mammal ComparisonMammal Comparison

http://mulan.dcode.org/

Slide Courtesy of Martien Groenen, Wageningen University

Sequence identity plot (50 - 100 %)

Potential Enhancers


Dissecting the Genetics of Complex TraitsDissecting the Genetics of Complex Traits–– QTL to QTN, but how much variation is structural in origin?QTL to QTN, but how much variation is structural in origin?

Research ToolsResearch Tools–– Functional GenomicsFunctional Genomics–– Comparative GenomicsComparative Genomics–– Systems Biology Systems Biology –– ““the legacy of quantitative geneticsthe legacy of quantitative genetics””–– Most knowledge will come from model species, butMost knowledge will come from model species, but……

These new tools are accelerating discoveryThese new tools are accelerating discoveryChallenges for optimal combination of quantitative and Challenges for optimal combination of quantitative and molecular information (MAS and GAS)molecular information (MAS and GAS)EpigeneticsEpigenetics

«« polar polar overdominanceoverdominance »»

Michel George’s groupSlide courtesy of J. P. Renard

The CLPG (callipyge) muscle The CLPG (callipyge) muscle hypertrophy phenotype hypertrophy phenotype A single base mutation resulting in muscle hypertrophy but only for heterozygous animals inheriting the paternal mutated allele

Charlier et al. 2001


GenomeGenome--Wide SelectionWide Selection–– Predicts merit from many marker Predicts merit from many marker (~30k(~30k markers)markers)–– Becoming affordableBecoming affordable–– Back to the blackBack to the black--box approachbox approach–– Uncertainty over new risks, e.g. locus specific Uncertainty over new risks, e.g. locus specific

inbreedinginbreedingHostHost--Pathogen InteractionsPathogen Interactions–– Real progress being made, but a huge opportunityReal progress being made, but a huge opportunity

GM and CloningGM and Cloning–– Divergent views on the priority for researchDivergent views on the priority for research


Societal IssuesSocietal Issues–– Genomics and pharming seem OKGenomics and pharming seem OK–– Major issue is GM animals for foodMajor issue is GM animals for food–– Differences in attitude USDifferences in attitude US--EU on cloning for EU on cloning for

foodfood–– Risk/benefit attitudes key to future acceptabilityRisk/benefit attitudes key to future acceptability

The Way ForwardThe Way Forward

Very close concordance between USDA Animal Very close concordance between USDA Animal Genomics Strategic Plan and EU scientistsGenomics Strategic Plan and EU scientists’’views of priorities:views of priorities:–– Comparative genomicsComparative genomics–– Systems biologySystems biology–– Infectious Disease and hostInfectious Disease and host--pathogen interactionspathogen interactions–– GenomeGenome--enabled animal improvementenabled animal improvement

EU still to develop the Strategic Research EU still to develop the Strategic Research Agenda for the Agenda for the ‘‘Farm Animal Breeding and Farm Animal Breeding and Reproduction Technology PlatformReproduction Technology Platform’’ (FABRE)(FABRE)Priorities of the SRA might be a bit broaderPriorities of the SRA might be a bit broader

The Way Forward The Way Forward -- 22Are there things that we can do better, cheaper or sooner Are there things that we can do better, cheaper or sooner if we collaborate?if we collaborate?Strong agreement that transatlantic collaboration should Strong agreement that transatlantic collaboration should be encouragedbe encouragedTaskTask--Force Partners asked to consider how this might be Force Partners asked to consider how this might be encouraged through funding mechanismsencouraged through funding mechanisms–– Shared costs of tools/resourcesShared costs of tools/resources

Genome sequencingGenome sequencingCuration of genomesCuration of genomesDevelopment of SNP PanelsDevelopment of SNP PanelsPopulations with expensive phenotypesPopulations with expensive phenotypes

–– People movementPeople movement–– Competitive grants (E.g. Human Frontier Science)Competitive grants (E.g. Human Frontier Science)

The Way Forward The Way Forward -- 33Strong agreement that genomic approaches to reducing Strong agreement that genomic approaches to reducing the impact of endemic disease is a high priority:the impact of endemic disease is a high priority:BenefitsBenefits–– Animal welfareAnimal welfare–– EconomicEconomic–– EnvironmentalEnvironmental–– Food safetyFood safety–– (food quality)(food quality)

ApproachesApproaches–– Selection for resistance/resilienceSelection for resistance/resilience–– Better diagnostics and vaccinesBetter diagnostics and vaccines

And Finally And Finally ……

Animal breeders and research groups have Animal breeders and research groups have phenotypically divergent populations that can phenotypically divergent populations that can help the wider community to dissect the genetics help the wider community to dissect the genetics of complex traitsof complex traits

““Animal breeders have performed an Animal breeders have performed an unprecedented phenotype driven mutant screenunprecedented phenotype driven mutant screenfor > 10,000 years: behaviour, morphology, for > 10,000 years: behaviour, morphology, physiology, pathology, physiology, pathology, …”…” Michel GeorgeMichel George

Thank You for Your AttentionThank You for Your Attention

www.genesiswww.genesis--faraday.orgfaraday.org

report of a workshop on “the future of livestock...

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