GENOMIC SELECTION IN DAIRY CATTLE
Theory and Application
OscarGonzálezRecio
May 11th 2016
Genomic Selec+on
Popula3on
Phenotypes
GEBV,parentageverifica3on,deleterioushaplotype
Imputa3on
Es3matemarker,LD,orlinkageeffects
• Largerbreedingvalueaccuraciesfortradi3onaltraits
• GEBVfornewtraits• Genomicma3ng• Reducegenera3onalinterval• Increasegene3cgain
Current state
• Officialgenomicevalua3onsinmostcountries• Siresofsiresareselectedwithoutprogenytestavailable
Reducegenera+onintervalin42mo.!!
Not only genomic breeding values
• Gene3cTestforDUMPS,BLAD,BRACHYSPINA,CVM,CITRULINEMIA• Fer3lity-relatedhaplotypes• Redandpolledfactors• Lactoglobulinesandmilkproteins• Freemar3n(infer3le)heifers• Parentageverifica3ontoimprove/completeherdbooks(forimprovedtradi3onalevalua3ons)
Gene+c progress
Gene+c progress
Nicepace
Watchforotherconsequencesontraitswearenotcurrently
considering
On going Projects
• RoleofRareVariants
• ImproveFeedEfficiencyandreduceMethaneEmissions
• Adapttochangingenvironment:HeatTolerance
Role of Rare Variants in non-produc+ve traits
• Morerelevantin“secondary”traits
Commonvariants Pedigree Uncommonvariants Rarevariants Fat(kg) 83% 14%** 0% 3%† Milk(L) 77% 23%** 0% 0%
Protein(kg) 76% 23%** 0% 1% DaysOpen(d) 84% 2% 0% 14%**
(Gonzalez-Recioetal.,2015.PloSONE)
Role of Rare Variants in non-produc+ve traits
• Morerelevantin“secondary”traits• Rarevariantsarefrequent,andfrequentlyaresequencingerrors
(Gonzalez-Recioetal.,2015.PloSONE)
Role of Rare Variants in non-produc+ve traits
• Improvingimputa3onaccuracyofrarevariants
• Includerarevariantsingenomicevalua3ons
On going Projects
• RoleofRareVariantsinnon-produc3vetraits
• ImproveFeedEfficiencyandreduceMethaneEmissions
• Adapttochangingenvironment:HeatTolerance
Improve Feed Efficiency and reduce Methane Emissions
• Feedresources• Averagemilkyield
FAO(2014)
Improve Feed Efficiency and reduce Methane Emissions
• Feedresources• Roughageinra3on(%)
FAO(2014)
Improve Feed Efficiency and reduce Methane Emissions
• Feedresources• Feedcost
FAO(2014)
Improve Feed Efficiency and reduce Methane Emissions
• MethaneisaGHGwithhea3ngpowerx21-28,comparedtoCO2
• Entericfermenta3onmakesupto25%oftotalmethaneemissionsfromagriculture
• Wastesourceoffeedenergy
Improve Feed Efficiency and reduce Methane Emissions
Hostgene3cs
Feedefficiency
Methane
Rumenphysiology
Microbiome
• Studytherela3onshipbetweenfeedefficiency,methaneemissionsandmicrobiomecomposi3onandtheinfluenceofthehost’sgene3cs
• 550animalswithmicrobiome16Sandmethaneemissions
• Feedefficiencyinassociatedfarmandmetagenome
On going Projects
• RoleofRareVariantsinnon-produc3vetraits
• ImproveFeedEfficiencyandreduceMethaneEmissions
• Adapttochangingenvironment:HeatTolerance
Adapt to changing environment: Heat Tolerance
• Researchteam:
• MaríaJ.Carabaño,ManuelRamón,ClaraDíaz,MalenaSerrano,JuanManuelSerradilla,etal.
• HediHammami,BetkaLogaretal.
Adapt to changing environment: Heat Tolerance
• Thermotolerance–gene3cvariability
HeatSuscepLble
HeatTolerant
HeatSuscepLbleHeatSuscepLble
HeatTolerant
ChangesingeneLcvaluealongaveragedailytemperatureforhigh,averageandlowproducLvecowsinSpanishH-Friesian
HeatTolerant
Adapt to changing environment: Heat Tolerance
• Thermotolerance–GxEinterac3onGxESpainvs.otherEUcountriesatdifferentvaluesoftemperature-humidityindex(THI)forproteinyield
GxEcomfort(10ºC)–othertemperaturesSpanishH-Friesian
GxEunderHS
Adapt to changing environment: Heat Tolerance
• Thereisgene3cvariabilityoftolerancetoHSmeasuredfrommilkrecords
• Thegene3cbackgroundofmilkproduc3on(andcomponents)changesunderheatstressàGxE
• Con3nuedselec3onforhighyieldsisexpectedtodeteriorateadapta3ontohightemperatures
• Iden3fica3onofheattolerancemeritindependentfrommilkproducLonrequiresoffinerphenotypes(physiologicalmeasures)anduseof-omicsàNewproject
Fer+lity
Fer+lity recover
PhenotypictrendinSpain
Gene3ctrendforESPsiresWorldtrendforcalvinginterval
New challenges
• FurtherincreaseofGEBVaccuracy• Adop3onofnewtechnologies–precisionfarming• Reducetheenvironmentalimpactofdairyproduc3on• New-omics
New challenges
• FurtherincreaseofGEBVaccuracy• Adop3onofnewtechnologies–precisionfarming• Reducetheenvironmentalimpactofdairyproduc3on• New-omics
Further increase of GEBV accuracy and genomic evalua+on systems
=1
Further increase of GEBV accuracy and genomic evalua+on systems • Reducetheoveres3ma3onofgenomicevalua3onfortopsires• Sequencedata
• Morethan1500animalssequencedRun5• Smallincreases0-5accuracypoints• Newanddifferentstrategies
• Mul3breedgenomicevalua3ons• Smallpopula3ons• Closelyrelatedorsizereducedpopula3ons• Largeordistantpopula3ons
• Lowheritabletraits• Weretoldthatmuchmoreincreasewaspossible.Butnotalwaysthecase.• Workonbenerphenotyping
New challenges
• FurtherincreaseofGEBVaccuracyandgenomicevalua3onsystems• Adop3onofnewtechnologies–precisionfarming• Reducetheenvironmentalimpactofdairyproduc3on• New-omics
Adop+on of new technologies – precision farming • MIR
• Predictlactose,caseins,proteins,milkureanitrogen,PUFA&MUFA
• Hormones• Othermilkmetabolites
• Onfarmsensors• Pedometersandcollars• Sniffersandlaserformethaneemissions• Weathercondi3ons(T,RH,P)
• Internetofthings• Real3meinforma3ontothefarmer• ITandmul3disciplinary
MethaneemissionsHeatstress
FerLlity
Behavioran
d
environmental
informaLon
New challenges
• FurtherincreaseofGEBVaccuracyandgenomicevalua3onsystems• Adop3onofnewtechnologies–precisionfarming• Reducetheenvironmentalimpactofdairyproduc3on• New-omics
Reduce the environmental impact of dairy produc+on • Animalfeedresourcescompe3ngwithhumanediblefood• Compe33onforlandincreases• Reducewasteandemissions
• Methaneemissions• Slurrypollu3on• Usean3bio3cs
• Improveconsumer’sacceptabilityofanimalproduc3onanddairyproducts
Reduce the environmental impact of dairy produc+on • Nomiracles
• Manytraits,slowgene3cprogress
• Selec3onindices40-50%weighttoproduc3on• Theother50%tolongevity,fer3lity,diseaseresistance,feedefficiency,temperament
• Farmers=EUinterest?
• Whatarethefuturecondi3onsgoingtobe?• efficiencyatproducingalotofmilkwithHighqualityforageandconcentrate• produceasmuchasyoucanwithPoorQF• applica3onofcarbontaxesonlivestockfarming
Manytraitsselec+ondependonthesecondi+ons
New challenges
• FurtherincreaseofGEBVaccuracyandgenomicevalua3onsystems• Adop3onofnewtechnologies–precisionfarming• Reducetheenvironmentalimpactofdairyproduc3on• New-omics
New -omics
SNPs
Microbiome
EpigeneLcs
RNAseq
SequencingRareA
lleles
New -omics
SNPs
Microbiome
EpigeneLcs
RNAseq
SequencingRareA
lleles
Epigene+cs
• 1942.Waddington.“thebranchofbiologythatstudiesthecausalinterac3onsbetweenthegenesandtheirproductswhichbringthephenotypesintobeing”.
• Roleindevelopmentandenvironmentalinfluence
• 2016-• Notconsensusonanuniquedefini3onofepigene3cs• Richards(2006).-ThestudyofpossiblyheritablechangesingeneexpressionthatarenotcausedbychangesinDNAsequence
• ‘Epigene3cs’commonlyusedasa‘generegula3on’term–Worthit?
Epigene+cs
• Epigene3cinforma3oncanbethoughtasthegrammarororthographyoftheDNAalphabetbecauseepigene3cmarksareregula3onmechanismassociatedwithgenesilencing,expression,chroma3nremodellingorimprin3ng.
ESTAESTÁ
BEBEBEBÉCÍRCULO
CIRCULÓAGTCCGCTAATAGTCCmGCTAAT
Epigene+cs
• Occursmainlyduringgesta3onandembryodevelopment• Relatedtocellulardifferenta3on
• Occurs‘denovo’alsothroughoutlife3me(builtbyenvironment)• Serveinothergeneac3va3on
• Diet• Managamentprac3ces• Stress
CH3
CH3
Methylase
Demethylase
Environment
diet
social
Rearing
Manage
ment
GENE
TICS
Epigene+cs
• Inheritedsomawide,butnottransgenera3onal.Veryfewexamplesoftransgenera3oninheritancefurtherthan3genera3ons,noneinmammals
• Epigene3cmarksareerasedduringmeiosis• Fewmightescape,buttheireffectisunclearanddissapearinthenextgenera3on(erase)
• Varonaetal.(2015)showedneglibleepigene3cvarianceinbeefcanle
Germ cells
ENVIRONMENTAL EFFECTS
Epigene+cs
• Poten3aluseandapplica3onsinanimalbreeding
1. Monitoringlife3memethyla3on,andstudytheirimpactonproduc3veandeconomictraits.Interferonthemethyla3onprocess(promoteorremove)
2. Includeepigene3cinforma3oningene3cevalua3onforalargeraccuracyanddiscriminatebtwheritablevsnon-heritableinforma3on
Epigene+cs
• Poten3aluseandapplica3onsinanimalbreeding3. EnvironmentalxEpigene3cxGenotypeInterac3onsduringembryo
development• candeterminetheadultlifeoftheindividual(Gluckmanetal.,2008;Burdgeetal.,2011;Bach,2012)
Cowsfromnon-lacta3ngdamswhilepregnantproducedmoremilkandlivedlongerinherds(González-Recioetal.,2012)
Epigene+cs
• Poten3aluseandapplica3onsinanimalbreeding
4. Epigene3cstatusaphenotypeitselfforthepredic3onoffuturephenotypes(GoddardandWhitelaw,2014)
5. Crossbreeding• Maternalandpaternallinesselectedonepigene3cstatuses-Ma3ngs(GoddardandWhitelaw,2014)
6. Selec3onofgenotypesthatfavorsomecertainepigene3cstatus(González-Recio,2012)