Genomic Selection in Dairy Cattle Dairy Cattle AQUAGENOME AQUAGENOME Applied Training Workshop, Sterling Hans Daetwyler, The Roslin Institute and R(D)SVS
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Genomic Selection in Dairy CattleDairy Cattle
AQUAGENOMEAQUAGENOMEApplied Training Workshop, Sterling
Hans Daetwyler, The Roslin Institute and R(D)SVS
Overview• Dairy introduction
T diti l b di• Traditional breeding• Genomic selection• Advantages• DisadvantagesDisadvantages• Genomic selection around the world
S mmar• Summary
Dairy Cattle • Most are specialised dairy breeds
– Holstein, Jersey, Brown Swiss, Ayrshire, etcHolstein, Jersey, Brown Swiss, Ayrshire, etc
• Some dual purpose• Some dual purpose– Simmental, Montbeliarde,
N d tNormande, etc
Dairy Industry• Relies very heavily (>80%) on artificial
insemination (AI)insemination (AI)• Nucleus herds exist but a large part of
b di i ill d b f b dbreeding is still done by farmer breeders• Global exchange of genetic material
between countries and AI companies– International genetic evaluation g
Traits selected for• Production
– Milk, fat and protein yield...Milk, fat and protein yield...
• Conformation• Conformation– Udder, legs, capacity...
• Functional & Health– Somatic cell score, fertility,....
Cornerstone of genetic progressg p g
• AI Companies increase the accuracy ofAI Companies increase the accuracy of selection through progeny testing.– Young bulls sire approx 100 daughters whichYoung bulls sire approx. 100 daughters which
provide information for their EBV once the daughters produce records
– Only 1 in 10 (or less) of bulls return to active service
– Very costly
Life cyclesBullBull
Birth 1 yr 2 yr 5 yr 10 yr
Bull isprogeny tested
Son is progenytestedDaughters born
Selected on parent avg
Cow
progeny tested testedg
Birth 1 yr 2 yr 4 yr 7 yr
Gives BirthGives Birth Son is progenytested
Daughter GivesBirth
Traditional Breeding
EstimationPedigree + BreedingV lEstimationRecords Value
• Accuracy increased with:• Own phenotypic recordsOwn phenotypic records• Information on relatives (sibs, progeny,…)
Traditional Breeding
• Works well in:– Med.- high heritability traits– Own records or progeny data is available
• Less effective – Low heritability traits, sex limited traits– Young animals (no records, no progeny)Young animals (no records, no progeny)
Genotypic Information• Thousands of single nucleotide
polymorphisms (SNP) are now available in imany species
• SNP have 2 alleles or gene variants
1 22 1 2 21
12 2 1 1 2 212 2 1 1 2 2
Genotypic Information• Thousands of single nucleotide
polymorphisms (SNP) are now available in y ( )many species
1 22 1 2 211 22 1 2 21
1Recode 1 20 11 0
12 2 1 1 2 2
1Recode 1 20 11 0
Genotype Data for yElevation - Chromosome 1
1000111220020012111011112111101111001121100020122002220111120210120021112211002111200111100101101101022001100220110112002011010202221211221020100111000112202212221120211201202010020220200002110001120201122111211102201111000021220200201002022020000211000112020112211121110220111100002122020002210120200022112201110121001112111021121100201021000220002201000201100002202211022112101121110122220012112122200200020020202012221100222222200221211112100211112001101110112002022200011120110102111212111020221002112012110011111021112110211122000101101110202200221110102011121111011202102102121101102212200121101121101202201100222002100211000111002110211011100022200202212121100022201020022221212211211120021021101110002220020221212110002220102002222121221121112002011020200122222211221202121121011001211011020022000200100200011110110012110212121112010101212022101010111110211021122111111212111210110120011111021111011111220121012121101022202021211222120222002121210121210201100111222121101• From Filippo Miglior, Canadian Dairy Network.
The Opportunity• Genotyping gives us ‘picture/snapshot’ of
the genetic makeup of an animalthe genetic makeup of an animal• The more SNP the clearer the picture (up to a limit)
• This new source of information can now (or soon) be used in genetic evaluation by:(or soon) be used in genetic evaluation by:– Combining genotyping data with traditional
pedigree and phenotypic recordspedigree and phenotypic records
Method• Meuwissen et al., Genetics, 2001
– Divide the genome into many segments (each g y g (with 1+ markers)
– Estimate the genetic effect of each segment g gfrom a sample of individuals
• Many small black boxes– Genotype another population sample and
sum the segment effects to get a breeding l f hvalue for each
How is this different?Pedigree +Records +
GenomicBreedingRecords +
Genomic Datag
ValueEstimate SNPeffects
How is this different?Pedigree +Records +
GenomicBreedingRecords +
Genomic Datag
ValueEstimate SNPeffects
Genomic BreedingValues for animalsWITHOUT records!WITHOUT records!
2 Main Genomic Estimation Methods• Genomic BLUP
– Easy to implement because similar to classic– Easy to implement because similar to classic BLUP
• Bayesian methodsMore complicated– More complicated
– May have higher accuracy than GBLUPPapers say yes practice says not so much• Papers say yes, practice says not so much…
Advantages of Genomic Selection
• Increase genetic gainB i i f l ti– By increasing accuracy of selection
• Parent avg 40%, Genomic BVs higherB d i th ti i t l– By reducing the generation interval
• Select animals before they are of productive and/or reproductive agereproductive age
• Reduce/eliminate the need for progeny testing– Reduces cost
Life cyclesBullBull
Birth 1 yr 2 yr 5 yr 10 yr
Bull isprogeny tested
Son is progenytestedDaughters born
Selected on parent avg
Cow
progeny tested testedg
Birth 1 yr 2 yr 4 yr 7 yr
Gives BirthGives Birth Son is progenytested
Daughter GivesBirth
Life cyclesBull Select Select Select Great-Bull
Birth 1 yr 2 yr 5 yr 10 yrSons here
Select Grand-sons
Select Greatgrand-sons
Bull isprogeny tested
Son is progenytestedDaughters born
Selected on parent avg
Cow
progeny tested testedg
Birth 1 yr 2 yr 4 yr 7 yr
Gives BirthGives Birth Son is progenytested
Daughter GivesBirth
Advantages• Lower rate of inbreeding per generation
(Daetwyler et al., JABG, 2007)( y )– Moves from family selection to individual selection– Example:
• Parent average same for full sib newborns• Genomic BV different for full sibs
– If generation intervals are shortened substantially then annual inbreeding rates could be higher
Inbreeding rates of methods3
Phenotypic Sel.
2
e pe
r gen
. (%
)
Classic BLUP
Genomic Sel.
1
nbre
edin
g ra
te
00.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
I
Daetwyler et al., J. Anim. Breed. Genet., 2007
0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
Heritability
Advantagesg• Once marker effects are estimated they
b d f f tican be used for a few generations – BUT accuracy will reduce in each generation
if t ti t dif not re-estimated• Selection on novel traits, expensive
phenotyping• New breeding strategiesg g
Disadvantages• New method, not fully proven and tested• Need to genotype a sufficiently large set ofNeed to genotype a sufficiently large set of
animals for accurate marker estimates (Daetwyler et al., PLoS One, 2008)
• Lower heritability more records needed
• Marker estimates must be estimated in population that they will be used in
• Across breed accuracy low
Disadvantages• Genotypes still costly (125£ dairy)• Some species have no dense markerSome species have no dense marker
maps yet• When generation intervals are already low• When generation intervals are already low
genetic gain due to genomic selection will be lessbe less
• In large litters accuracy can be gained f i f ib l d t f GSfrom info on sibs less advantage of GS
Genotyping• Illumina BovineSNP50TM BeadChip
– 58,000 genetic markers, equally spaced – 38,416 used in genomic predictions
• Total of one-third non-informative (currently) or without variation across dairy cattlewithout variation across dairy cattle
– Openly commercialized to several laboratories in various countries
– Current genotyping cost ≈$250 USD per animal
Miglior, Can. Dairy Network
Genomic selection around the ldworld
• USA & Canada (N.A.) Collaboration• New Zealand (LIC)• Netherlands (CRV)Netherlands (CRV)• Australia (ADHIS & co.)
D k & S d (Viki G ti )• Denmark & Sweden (Viking Genetics)• Several other countries likely to follow
fairly soonMiglior, Can. Dairy Network
Australian resultsTable 1. Accuracy of genomic breeding values calculated at time of birth for Genetic Australia’s 2003 progeny test team with two genomic selection methods, BLUP and a Bayesian method (BAYES).
Trait
Records in reference
populationNumber ofSNPs used
Sire pathway EBV GBLUP GBayesA
AUS SelectionAUS Selection Index 637 3889 0.62 0.66 0.69
AUS Profit Ranking 635 3414 0.59 0.73 0.74
Protein yield 637 4055 0.53 0.67 0.69
Protein % 637 4369 0.45 0.54 0.60
Fertility 332 3090 0.40 0.42 0.37
Hayes et al, Review, JDS, 2008
World wide results• North America
– GS Accuracy avg 71%, PA 52%Diff b t BLUP d B i 1%– Difference between BLUP and Bayesian was 1%
• Netherlands• Netherlands– Large increases in accuracy of GS over PA– Use Bayesian methodsy
• New Zealand
Hayes et al, Review, JDS, 2008– GS accuracy avg 70 – 80%, PA 58%
Higher risk vs. Lower risk• How will different AI companies use it?• Examples:Examples:
– LIC: Reduce progeny testing from 300 to 100-150 bulls, emphasis on DNA teams150 bulls, emphasis on DNA teams
– Recent recall announcement for HO team(s)
– CRV: Reduce progeny testing from 500 to p g y g300 bulls, reduce YS incentives
– North-American units likely to use a more yconservative transitional approach
Miglior, Can. Dairy Network
Possible strategy• Genotype a large number of elite females
and bull calvesand bull calves• Put the best GEBV bulls into organized
progeny testingprogeny testing • Use the best of those as sires of sons, and
in teams for the GEBV bull marketin teams for the GEBV bull market• Use the best proven bulls for the proven
bull marketbu a et
Miglior, Can. Dairy Network
How can we do better?• Genotype more SNP to get clearer
‘picture’ of genetic variation (up to a limit)picture of genetic variation (up to a limit)• Genotype and get records for more
i lanimals• Refine estimation methods
– Determine when to use BLUP or Bayes• Develop new estimation methodsp
Summary• Dairy industry uniquely suited for genomic
selection– Faster genetic progress possible with higher
accuracy and shorter generation intervals• Several countries are implementing
genomic selection– Hybrid systems merging classic and genomic
selection
SummaryU f l f i l ti d d• Usefulness of genomic selection depends on:
P l ti t t /hi t– Population structure/history• Size of sib families• Generation intervalGeneration interval
– Availability of dense marker mapsy p
– Availability of many genotyped individuals with records
Acknowledgements• Filippo Miglior, Canadian Dairy Network,
Guelph
B H Vi t i D P i• Ben Hayes, Victoria Dep. Primary Industries, Melbourne
• And my funding...y gSABRETRAIN is funded by the Marie Curie Host fellowships for Early Stage Research Training funding mechanism, as part of the 6th Framework Programme of the European Union European Commission.
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