GENOMIC SELECTION IN DAIRY CATTLE Theory and Application€¦ · • 1942. Waddington. “the...

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)