2007 paul vanraden 1, george wiggans 1, curt van tassell 2, tad sonstegard 2, jeff o’connell 1,...
TRANSCRIPT
2007
Paul VanRadenPaul VanRaden11, George Wiggans, George Wiggans11, Curt Van Tassell, Curt Van Tassell22, Tad , Tad SonstegardSonstegard22, Jeff O’Connell, Jeff O’Connell11, Bob Schnabel, Bob Schnabel33, Jerry Taylor, Jerry Taylor33, and , and Flavio SchenkelFlavio Schenkel44, , 1Animal Improvement Programs Lab and 2Bovine Functional Genomics Lab, USDA Agricultural Research Service, Beltsville, MD, USA, 3U. Missouri, Columbia, 4U. Guelph, ON, [email protected]
2008
North American Cooperation in North American Cooperation in Genomic Prediction Genomic Prediction
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Sequencing and GenotypingSequencing and Genotyping
Cattle genome sequenced in 2004• 30 chromosome pairs (including X,Y)• 3 billion letters from each parent
Illumina BovineSNP50 BeadChip• 58,000 genetic markers in 2007• 38,416 used in genomic predictions• Current cost < $250 per animal
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History of Genomic CooperationHistory of Genomic Cooperation
1992 USDA request for CAN, USA AI companies to join Dairy Bull DNA Repository maintained at U. Illinois• CIAQ (Brian Van Doormaal) provided 1110
straws from 110 bulls
1999 Cooperative Dairy DNA Repository maintained at Beltsville, MD• Semex and Alta contributed semen for all
progeny tested bulls
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CDDR ContributorsCDDR Contributors
National Association of Animal Breeders (NAAB, Columbia, MO)• ABS Global (DeForest, WI)• Accelerated Genetics (Baraboo, WI)• Alta (Balzac, AB)• Genex (Shawano, WI)• New Generation Genetics (Fort Atkinson, WI)• Select Sires (Plain City, OH)• Semex Alliance (Guelph, ON)• Taurus-Service (Mehoopany, PA)
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Genotype Data for ElevationGenotype Data for Elevation Chromosome 1Chromosome 1
10001112200200121110111121111011110011211000201220022201111202101200211122110021112001111001011011010220011002201101120020110102022212112210201001110001122022122211202112012020100202202000021100011202011221112111022011110000212202000221012020002211220111012100111211102112110020102100022000220100020110000220221102211210112111012222001211212220020002002020201222110022222220022121111210021111200110111011200202220001112011010211121211102022100211201211001111102111211021112200010110111020220022111010201112111101120210210212110110221220012110112110120220110022200210021100011100211021101110002220020221212110002220102002222121221121112002011020200122222211221202121121011001211011020022000200100200011110110012110212121112010101212022101010111110211021122111111212111210110120011111021111011111220121012121101022202021211222120222002121210121210201100111222121101
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Genotype Data from Inbred BullGenotype Data from Inbred BullChromosome 24 of MegastarChromosome 24 of Megastar
102122210102102101110211011211221121100220200022202000202022000002200202222022020000200202222220000202222000002202000020022002000000222200022220000000000020222022002000222020222220002202222222220000200220202220200020002200000000220222000000220020200022220020200200202022202222222202220200020220220222202022202020202200022002220220022200000220200002002002000200222220002222020200222002220200002020000002222202020000200200222200020220222200220002222022002222020200022022022220022200220002002202000002200220222000022000022000222202002222000220020020202202000222000222002220220220000022022002002002022000200022220220022200202202002222022200000202200020200202020002200220000022022200202220200022002000200022002002000200220222220022022000200002000200002022002022020020000222000022200200020022200002202200200220022022020202020202000222020002202002022022202200002020200002020200022222200222200020022022220000020220020200202022022020200002000200220220002200
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Close Inbreeding Close Inbreeding (F=14.7%)(F=14.7%): : Double Double Grandson of AerostarGrandson of Aerostar
Aerostar
Aerostar
Megastar
Chromosome 24
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Holstein Experimental DesignHolstein Experimental Design
Compute genomic evaluations and parent averages from 2003 data• 3576 older Holstein bulls born 1952-1998
Compare ability to predict daughter deviations in 2008 data• 1759 younger bulls born 1999-2002
Test results for 27 traits: 5 yield, 5 health, 16 conformation, and Net Merit
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Genotyped Holsteins (n=6005)Genotyped Holsteins (n=6005)As of April 2008As of April 2008
0
200
400
600
800
100019
50
1970
1990
1992
1994
1996
1998
2000
2002
2004
2006
2008
Year of Birth
Nu
mb
er o
f A
nim
als
Predictor
Predictee
Young
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Jersey and Brown SwissJersey and Brown Swiss
Jersey experimental design• Data from 579 bulls born before 1999 and
204 cows with data before 2003• Predict 352 bulls born during or after 1999
Brown Swiss experimental design• Data from 225 bulls born before 1999 • Predict 118 bulls born during or after 1999
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Genomic MethodsGenomic Methods
Direct genomic evaluation• Evaluate genotyped animals by summing
effects of 38,416 genetic markers (SNPs)
Combined genomic evaluation• Include phenotypes of nongenotyped
ancestors by selection index
Transferred genomic evaluation• Propagate info from genotyped animals to
nongenotyped relatives (not done yet)
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Significance Tests for Net MeritSignificance Tests for Net Merit
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Marker Effects for Net MeritMarker Effects for Net Merit
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Major Gene on Chromosome 18Major Gene on Chromosome 18Net Merit, Productive Life, Calving Ease, Stature, Strength, Rump WidthNet Merit, Productive Life, Calving Ease, Stature, Strength, Rump Width
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Marker Effects for MilkMarker Effects for Milk
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Marker Effects for Final ScoreMarker Effects for Final Score
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Reliability Gain by BreedReliability Gain by Breed
Trait HO JE BS
Net merit 23 14 3
Milk 23 6 0
Fat 33 10 5
Protein 22 3 1
Fat % 43 31 10
Protein % 34 22 5
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Reliability Gain by BreedReliability Gain by Breed
Trait HO JE BS
Productive life 18 8 2
Somatic cell score 21 3 16
Dtr pregnancy rate 16 3 -
Final score 18 4 -
Udder depth 35 11 3
Foot angle 14 8 -
Stature 26 8 3
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Reliability Gains for Proven BullsReliability Gains for Proven Bulls
Proven bulls included in test had:• >10 daughters in August 2003• >10% increase in reliability by 2008• Numbers of bulls in test ranged from
104 to 735 across traits• Predicted the change in evaluation
Significant increase in R2 (P < .001) for 26 of 27 traits
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Net Merit by Chromosome for O ManNet Merit by Chromosome for O ManTop bull for Net MeritTop bull for Net Merit
-40
-20
0
20
40
60
80
X 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30
Chromosome
NM
$
NM$
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SNPs on X ChromosomeSNPs on X Chromosome
Each animal has two evaluations:• Expected genetic merit of daughters• Expected genetic merit of sons• Difference is sum of effects on X• SD = .1 σG, smaller than expected
Correlation with sire’s daughter vs. son PTA difference was significant (P<.0001), regression close to 1.0
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X, X, YY, , Pseudo-autosomalPseudo-autosomal SNPs SNPs
487 SNPs
35 SNPs
0 SNPs
35 SNPs
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Clones and Identical TwinsClones and Identical Twins21HO2121, 21HO2125, 21HO2100, CAN6139300, CAN613930321HO2121, 21HO2125, 21HO2100, CAN6139300, CAN6139303
Traditional Genomic
Bull Dtrs NM$ REL NM$ REL
Triton - ETN 98 -363 82 -371 91
Triad - ETN 26 -306 68 -370 91
Trey - ETN 108 -395 83 -371 91
Loyalty 108 -185 78 -196 87
Lauriet 83 -203 76 -196 87
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Value of Genotyping More Value of Genotyping More SNPSNP9,604 (10K), 19,208 (20K), and 38,416 (40K) SNP9,604 (10K), 19,208 (20K), and 38,416 (40K) SNP
REL of PA
Genomic REL
Trait 10K 20K 40K
Net Merit $ 30 48 50 53
Milk yield 35 53 56 58
Fat yield 35 64 66 68
Protein yield 35 54 56 57
Productive Life 27 38 41 45
SCS (mastitis) 30 45 47 51
Dtr Preg Rate 25 37 39 41
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Value of Genotyping More BullsValue of Genotyping More Bulls
Bulls R2 for Net Merit
Predictor Predictee PA Genomic Gain
1151 251 8 12 4
2130 261 8 17 9
2609 510 8 21 13
3576 1759 11 28 17
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SimulatedSimulated Results ResultsWorld Holstein PopulationWorld Holstein Population
15,197 older and 5,987 younger bulls in Interbull file
40,000 SNPs and 10,000 QTLs
Provided timing, memory test
Reliability vs parent average REL• REL = corr2 (EBV, true BV) • 80% vs 34% expected for young bulls• 72% vs 30% observed in simulation
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Expected vs Observed ReliabilityExpected vs Observed ReliabilityHolsteinsHolsteins
Reliability for predictee bulls • Traditional PA: 27% average across traits• Genomic: 63% expected vs. 50% observed• Observed range 78% (fat pct) to 31% (SCE)• PTA regressions .8 to .9 of expected
Multiply genomic daughter equivalents by .7 to make expected closer to observed • For example, 16 * .7 = 11• Include polygenic effect, less than 5%
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Genetic ProgressGenetic ProgressHolsteinsHolsteins
Assume 60% REL for net merit• Sires mostly 2 instead of 6 years old• Dams of sons mostly heifers with 60% REL
instead of cows with phenotype and genotype (66% REL)
Progress could increase by >50%• 0.37 vs. 0.23 genetic SD per year• Reduce generation interval more than
accuracy
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Genetic Evaluation AdvancesGenetic Evaluation Advancesand increases in genetic progressand increases in genetic progress
Year Advance % Gain
1935 Daughter-dam comparison 100
1962 Herdmate comparison 50
1973 Records in progress 10
1974 Modified cont. comparison 5
1977 Protein evaluated 4
1989 Animal model 4
1994 Net merit, PL, and SCS 50
2008 Genomic selection >50
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Genetic Evaluation TimingGenetic Evaluation Timing
CAN, USA had same genetic evaluation schedule since early 1980’s• Same with 2X, 4X, and 3X releases per year• Files exchanged 1 week before a combined
release, 1993-1996 Interbull evaluations began in 1995
• MACE methods developed in CAN• Correlation estimation programs from USA • First director: PhD in USA, post-doc in CAN• MACE conformation by N.A. Consortium
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CAN, USA Combined DataCAN, USA Combined Data
Evaluations tested and reported in 1991• Banos and Wiggans, Robinson and
Wiggans, Powell et al, Wiggans et al• Both countries used Cornell computer
Animal models applied to yield data of Jerseys and Ayrshires
Correlations .98 and .96 between combined vs. converted evaluation
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ConclusionsConclusions
Genomic predictions significantly better than parent average (P < .0001) for all 26 traits tested
High reliability requires many genotypes and phenotypes
Close cooperation between CAN and USA will continue• Science, software, and data sharing
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AcknowledgmentsAcknowledgments
Genotyping and DNA extraction:• BFGL, U. Missouri, U. Alberta, GeneSeek, GIFV, and
Illumina
Computing: • AIPL staff (Mel Tooker, Leigh Walton, etc.)
Funding: • National Research Initiative grants
– 2006-35205-16888, 2006-35205-167012006-35205-16888, 2006-35205-16701• Agriculture Research Service• Contributors to Cooperative Dairy DNA Repository
(CDDR)
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CDDR ContributorsCDDR Contributors
National Association of Animal Breeders (NAAB, Columbia, MO)• ABS Global (DeForest, WI)• Accelerated Genetics (Baraboo, WI)• Alta (Balzac, AB)• Genex (Shawano, WI)• New Generation Genetics (Fort Atkinson, WI)• Select Sires (Plain City, OH)• Semex Alliance (Guelph, ON)• Taurus-Service (Mehoopany, PA)