1. John B. Cole Animal Improvement Programs Laboratory Agricultural Research Service, USDA Beltsville, MD 20705-2350 john.cole@ars.usda.gov March 2012 AIPL Update

2. Select Sires Sire Evaluation Committee, March 19, 2012 (2) Cole Topics Genomics overview April 2012 changes Accounting for bias Selection index adjustments Cow adjustments Calving traits update

3. Select Sires Sire Evaluation Committee, March 19, 2012 (3) Cole Whole-genome selection Use many markers to track inheritance of chromosomal segments Estimate the impact of each segment on each trait Combine estimates with traditional evaluations to produce genomic evaluations (GPTA) Select animals shortly after birth using GPTA Very successful worldwide

4. Select Sires Sire Evaluation Committee, March 19, 2012 (4) Cole Illumina genotyping arrays BovineSNP50 54,001 SNPs (version 1) 54,609 SNPs (version 2) 45,187 SNPs used in evaluation BovineHD 777,962 SNPs Only BovineSNP50 SNPs used >1,700 SNPs in database BovineLD 6,909 SNPs Allows for additional SNPs BovineSNP50 v2 BovineLD BovineHD

5. Select Sires Sire Evaluation Committee, March 19, 2012 (5) Cole Reliabilities for young Holsteins* *Animals with no traditional PTA in April 2011 0 1000 2000 3000 4000 5000 6000 7000 8000 9000 404550556065707580 Reliability for PTA protein (%) Number of animals 3K genotypes 50K genotypes

6. Select Sires Sire Evaluation Committee, March 19, 2012 (6) Cole Date SNP Estimation* Young animals** All animals BullsCows BullsHeifers 04-10 9,770 7,41516,007 8,630 41,822 08-1010,430 9,37218,65211,021 49,475 12-1011,29312,82521,16118,336 63,615 04-1112,15211,22425,20236,545 85,123 08-1116,51914,38029,09052,053112,042 09-1116,81214,41530,18556,559117,971 10-1116,83214,57331,86561,045124,315 11-1116,83414,71632,97565,330129,855 12-1117,28817,23633,86168,051136,436 01-1217,68117,41835,40474,072144,575 02-1217,71017,67936,59780,845152,831 *Traditional evaluation **No traditional evaluation Genotyped Holsteins

7. Select Sires Sire Evaluation Committee, March 19, 2012 (7) Cole What’s a SNP genotype worth? For the protein yield (h 2 =0.30), the SNP genotype provides information equivalent to an additional 34 daughters Pedigree is equivalent to information on about 7 daughters

8. Select Sires Sire Evaluation Committee, March 19, 2012 (8) Cole And for daughter pregnancy rate (h 2 =0.04), SNP = 131 daughters What’s a SNP genotype worth?

9. Select Sires Sire Evaluation Committee, March 19, 2012 (9) Cole High density update HD tests before and after GBR, ITA 342 HD animals with 636,967 SNPs 1,074 HD animals with 636K or 311K 1,510 HD animals with 311,725 SNPs REL gain above 50K for the 3 tests -0.5% decrease in REL using 342 HD +0.4% increase using 1,074 HD +1.0% increase using 1,510 HD

10. Select Sires Sire Evaluation Committee, March 19, 2012 (10) Cole Trait a Bias b bREL (%)REL gain (%) Milk (kg)−64.30.9267.128.6 Fat (kg)−2.70.9169.831.3 Protein (kg) 0.70.8561.523.0 Fat (%) 0.01.0086.548.0 Protein (%) 0.00.9079.040.4 PL (months)−1.80.9853.021.8 SCS 0.00.8861.227.0 DPR (%) 0.00.9251.221.7 Sire CE 0.80.7331.010.4 Daughter CE−1.10.8138.419.9 Sire SB 1.50.9221.8 3.7 Daughter SB− 0.20.8330.313.2 a PL = productive life, CE = calving ease and SB = stillbirth. b 2011 deregressed value – 2007 genomic evaluation. Holstein prediction accuracy

11. Select Sires Sire Evaluation Committee, March 19, 2012 (11) Cole April 2012 changes Genotypes from GGP included Revised weights used to combine information for genotyped animals Reduces evaluations of top young animals compared with older animals Reliabilities changed only slightly, but would decrease if DGV weights were reduced more Some regressions lower than expected, and the revised weights helped bring those into compliance with validation tests

12. Select Sires Sire Evaluation Committee, March 19, 2012 (12) Cole April 2012 changes, cont’d Reliabilities revised to agree more precisely with observed reliabilities from truncated data Published reliabilities for young Holstein animals were adjusted: -3 percentage points for yield traits +3 to 6 percentage points for fitness traits -7 to 10 percentage points for calving traits +1 percentage point for type traits

13. Select Sires Sire Evaluation Committee, March 19, 2012 (13) Cole April 2012 changes, cont’d Traditional PL evaluations for females less than 48 months of age not used in the genomic evaluation Eliminated large differences between genomic and traditional PL for some bulls Traditional DPR evaluations for genotyped cows less than 36 months of age now excluded from genomic evaluation Similar edit for CCR

14. Select Sires Sire Evaluation Committee, March 19, 2012 (14) Cole Some sources of bias Pre-selection bias Affects domestic and international evaluations Preferential treatment of bull dams Results in inflated PTA

15. Select Sires Sire Evaluation Committee, March 19, 2012 (15) Cole Expected value of Mendelian sampling no longer equal to 0 Key assumption of animal models References: Patry, Ducrocq 2011 GSE 43:30 Vitezica et al 2011 Genet Res (Camb) pp. 1–10. Bias from pre-selection

16. Select Sires Sire Evaluation Committee, March 19, 2012 (16) Cole Bulls born in 2008, progeny tested in 2009, with daughter records in 2012, were pre-selected: 3,434 genotyped vs. 1,096 sampled Now >10 genotyped per 1 marketed Potential for bias: 178 genotyped progeny 32 sons progeny tested Pre-selection bias now beginning

17. Select Sires Sire Evaluation Committee, March 19, 2012 (17) Cole 1-Step to incorporate genotypes Flexible models, many recent studies Foreign data not yet included Multi-step GEBV, then insert in AM Same trait (Ducrocq and Liu, 2009) Or correlated trait (Mantysaari and Stranden, 2010; Stoop et al, 2011) Foreign genotyped bulls included National methods to reduce bias

18. Select Sires Sire Evaluation Committee, March 19, 2012 (18) Cole Multi-step genomic methods Direct genomic value (DGV) Sum of effects for 45,187 genetic markers Does not include polygenic effect (USA) Does include the polygenic effect (CAN, others) Model: y = Xb + Zg + poly + e Combined genomic evaluation (GPTA) Include phenotypes not used in estimating DGV Selection index includes 3 terms per animal: (DGV + poly), traditional PTA, and subset PTA GPTA = w 1 (DGV + poly) + w 2 PTA + w 3 SPTA

19. Select Sires Sire Evaluation Committee, March 19, 2012 (19) Cole Combined GPTA GPTA = w 1 (DGV + poly) + w 2 PTA + w 3 SPTA (DGV + poly) = contribution from SNP effects PTA = contribution from the traditional evaluation SPTA = subset PTA estimated using pedigree relationships among the genotyped animals Terms combined using theoretical weights based on reliabilities Weights average 0.99 for DGV, 0.12 for EBV, and -0.11 for SBV

20. Select Sires Sire Evaluation Committee, March 19, 2012 (20) Cole Selection index examples Dam not genotyped, low GREL GPTA =.99 (DGV+poly) +.41 PTA -.40 SPTA Dam not genotyped, high GREL GPTA =.99 (DGV+poly) +.11 PTA -.10 SPTA Dam is genotyped GPTA = 1.00 (DGV+poly) +.00 PTA -.00 SPTA

21. Select Sires Sire Evaluation Committee, March 19, 2012 (21) Cole Proposal: Shift weight from DGV to SPTA Dam not genotyped, low GREL GPTA =.90 (DGV+poly) +.41 PTA -.31 SPTA Dam not genotyped, high GREL GPTA =.90 (DGV+poly) +.11 PTA -.01 SPTA Dam is genotyped GPTA =.90 (DGV+poly) +.10 PTA -.00 SPTA

22. Select Sires Sire Evaluation Committee, March 19, 2012 (22) Cole Results of shifting DGV weight Similar to adding more polygenic variance but easier computation Some genomic REL higher with.90 weight, but lower if <.80 weight Regressions of future on past data higher if DGV weight lower Highest animals have lower GPTAs with.90 weight

23. Select Sires Sire Evaluation Committee, March 19, 2012 (23) Cole Convert and exchange DYD g National GEBV and DYD g unbiased Can’t deregress GEBV without G Exchange similar to simple GMACE Other countries need DYD anyway Deregress, reregress EBVs in MACE Countries deregress MACE EBV Avoid bias by exchanging DYD g International bias reduction

24. Select Sires Sire Evaluation Committee, March 19, 2012 (24) Cole 6,743 bulls with no USA daughters Corr (National EBV, MACE EBV).77 before adding foreign data.995 after adding foreign data Few foreign bulls in JE reference population, so hard to test gain in REL of young bull GEBV Foreign data in 1-Step: results

25. Select Sires Sire Evaluation Committee, March 19, 2012 (25) Cole EvaluationRegression Squared Correlation Parent Average.73.436 Multi-Step GEBV.75.520 1-Step GEBV.85.520 Expected.93 1-Step vs multi-step Data cutoff in August 2008

26. Select Sires Sire Evaluation Committee, March 19, 2012 (26) Cole Holstein convergence much slower JE took 11 sec / round including G HO took 1.6 min / round including G JE needed ~1000 rounds HO needed >5000 rounds All-breed model without genomics Replace software used since 1989 Correlations >.995 with traditional AM Preliminary larger analyses

27. Select Sires Sire Evaluation Committee, March 19, 2012 (27) Cole Bias in cow evaluations Top cows over-evaluated compared to top bulls Parent averages over-estimate eventual evaluations of bulls Unreasonable estimates of SNP effects in PAR reflect sex effect Adjustment of evaluations of genotyped cows implemented April 2010 Adjustment made genotyped cows not comparable to non genotyped cows

28. Select Sires Sire Evaluation Committee, March 19, 2012 (28) Cole Genomic evaluation Deregressed traditional evaluations used for estimation of SNP effects Predictor population consists of animals with both genotypes and traditional evaluations Cows can be predictors Increases size of predictor population Requires that cow and bull evaluations be comparable

29. Select Sires Sire Evaluation Committee, March 19, 2012 (29) Cole Adjustment of cow evaluations US industry requested adjustment of all cow evaluations to restore comparability Desirable to leave estimates of genetic trend unchanged Variability of cow evaluations to be reduced Industry requested proposal in February for possible implementation in April 2011 Industry partners collaborated in developing and distributing information on the new adjustment

30. Select Sires Sire Evaluation Committee, March 19, 2012 (30) Cole Method Adjustment for Milk, Fat, and Protein only Mendelian Sampling (MS) = PTA - PA Deregressed Value = MS/R DE cow = DE tot – DE pa R = DE cow /(DE tot + k) SD of Deregressed Values of cows and bulls compared l Adj Var = SD bull /SD cow Varies with reliability

31. Select Sires Sire Evaluation Committee, March 19, 2012 (31) Cole Mean adjustment Calculate mean PA by birth year Adj Mean = factor*(PA – PA mean ) HO factor = -0.434 Dev adj = Adj Var *Deregressed Value + Adj Mean + PA HO Adj Var = 0.3165 + 1.433 * R cow R cow = DE cow /(DE cow + k) PTA adj = R*Dev adj + (1-R)*PA new PA new includes PTA adj of dam

32. Select Sires Sire Evaluation Committee, March 19, 2012 (32) Cole PTA milk for cows born in 2005 ADJNo ADJDifference -1500 -1000 -500 0 500 1000 1500 -1000-760-520-280-40200440680920 PA PTA

33. Select Sires Sire Evaluation Committee, March 19, 2012 (33) Cole Effect of reliability -400 -300 -200 -100 0 100 200 300 400 500 600 303234363840424446485052545658606264 PTA Reliability ADJ No ADJDifference

34. Select Sires Sire Evaluation Committee, March 19, 2012 (34) Cole Additional adjustment for genomics DGV – direct genomic value, sum of SNP effects Further adjust so Mean PTA = Mean DGV All cow adjustment not able to remove bias in cows selected to be genotyped Reduce adjusted PTA by following amounts HolsteinJersey & Brown Swiss Milk (lb)169.7165.9 Fat (lb)8.36.4 Protein (lb)4.25.8

35. Select Sires Sire Evaluation Committee, March 19, 2012 (35) Cole Possible further applications Additional breeds Ayrshire, Guernsey, Milking Shorthorn Additional traits Large SNP effects on PAR observed in type and functional traits Limitation with One-Step method Adjustment between traditional and genomic evaluations not possible

36. Select Sires Sire Evaluation Committee, March 19, 2012 (36) Cole Cow adjustment summary Improved adjustment of cow evaluations for use in genomic evaluations Accommodation of different population being genotyped with 3K chip Improved comparability of evaluations of genotyped and non genotyped cows Foreign cow evaluations not used in estimation of SNP effects

37. Select Sires Sire Evaluation Committee, March 19, 2012 (37) Cole Calving traits topics Proposed changes Multiple-trait evaluation Interbull trend validation Future research

38. Select Sires Sire Evaluation Committee, March 19, 2012 (38) Cole Calving traits Sire-maternal grandsire threshold model y = HY + YS + PS + Ys + Ym + s + m + e All parities combined into a single trait Low heritabilities, 2 to 8%

39. Select Sires Sire Evaluation Committee, March 19, 2012 (39) Cole Interbull trend validation Ensures evaluation results are in line with expectations Must pass every two years The US was failing the method 3 trend test If we don’t pass, we get kicked out

40. Select Sires Sire Evaluation Committee, March 19, 2012 (40) Cole How do we fix it? Wiggans et al. (2007) tried multiple- trait linear models Poor correlations w/other countries Did not implement New approach – first and later parities evaluated separately and blended into a single PTA Method may be too simple

41. Select Sires Sire Evaluation Committee, March 19, 2012 (41) Cole Results Bulls ranked similarly Reliabilities for bulls with little data decreased Good correlations with MACE for high-reliability bulls Poor correlations with test run results

42. Select Sires Sire Evaluation Committee, March 19, 2012 (42) Cole Decision We don’t have a good explanation for the drop in correlations May be way reliabilities are blended Errors found in trend-testing code Both models now pass validation Continue with current model until we figure our correlation issue

43. Select Sires Sire Evaluation Committee, March 19, 2012 (43) Cole Ongoing research Is there a link between use of sexed semen and stillbirths? What about effects of age at first calf on calving traits? What’s wrong with our correlations?

44. Select Sires Sire Evaluation Committee, March 19, 2012 (44) Cole Overall conclusions No changes made to calving traits evaluations All data are important We are working on biases in both cow and bull evaluations 1-step looks promising if we can get the calculations done

45. Select Sires Sire Evaluation Committee, March 19, 2012 (45) Cole Questions?