1. G.R. Wiggans Animal Improvement Programs Laboratory Agricultural Research Service, USDA Beltsville, MD george.wiggans@ars.usda.gov 2011 G.R. Wiggans DNA LandMarks User Group Meeting- Oct, 2011 (1) North American Dairy Cattle Genomic Selection Program

2. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (2) History of genomic evaluations l Dec. 2007BovineSNP50 BeadChip available l Apr. 2008First unofficial evaluation released l Jan. 2009Genomic evaluations official for Holstein and Jersey l Aug. 2009Official for Brown Swiss l Sept. 2010Unofficial evaluations from 3K chip released l Dec. 20103K genomic evaluations to be official l Sept. 2011 Infinium BovineLD BeadChip available

3. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (3) Cattle SNP Collaboration - iBMAC l Develop 60,000 Bead Illumina iSelect® assay w USDA-ARS Beltsville Agricultural Research Center: Bovine Functional Genomics Laboratory and Animal Improvement Programs Laboratory w University of Missouri w University of Alberta w USDA-ARS US Meat Animal Research Center l Started w/ 60,800 beads – 54,000 useable SNP

4. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (4) Chips l BovineSNP50 w Version 1 54,001 SNP w Version 2 54,609 SNP w 45,187 used in evaluations l HD w 777,962 SNP w Only 50K SNP used, w >1700 in database l LD w 6,909 SNP w Replaces 3K HD 50KV2 LD

5. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (5) Use of HD l Currently only 50K subset of SNP used l Some increase in accuracy from better tracking of QTL possible l Potential for across breed evaluations l Requires few new HD genotypes once adequate base for imputation developed

6. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (6) LD chip l 6909 SNP mostly from SNP50 chip w 9 Y Chr SNP included for sex validation w 13 Mitocondrial DNA SNP w Evenly spaced across 30 Chr l Developed to address performance issues with 3K while continuing to provide low cost genotyping l Provides over 98% accuracy imputing 50K genotypes l To be included in Nov genomic evaluation

7. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (7) Development of LD chip l Consortium included researchers from USA, AUS and FRA l Objective: good imputation performance in dairy breeds w Uniform distribution except heavier at chromosome ends w High MAF, avg MAF over 30% for most breeds w Adequate overlap with 3K

8. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (8) Responsibilities of requester l Insure animal is properly identified eg HOCANF000123456789 l Enroll animal with breed association or insure pedigree on animal and dam reaches AIPL l Collect clean, clearly labeled DNA sample l Get sample to lab in time to be included in desired month’s results l Resolve parentage conflicts quickly

9. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (9) Steps to prepare genotypes l Nominate animal for genotyping l Collect blood, hair, semen, nasal swab, or ear punch w Blood may not be suitable for twins l Extract DNA at laboratory l Prepare DNA and apply to BeadChip l Do amplification and hybridization, 3-day process l Read red/green intensities from chip and call genotypes from clusters

10. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (10) What can go wrong l Sample does not provide adequate DNA quality or quantity l Genotype has many SNP that can not be determined (90% call rate required) l Parent-progeny conflicts w Pedigree error w Sample ID error (Switched samples) w Laboratory error w Parent-progeny relationship detected that is not in pedigree

11. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (11) Lab QC l Each SNP evaluated for w Call Rate w Portion Heterozygous w Parent-progeny conflicts l Clustering investigated if SNP exceeds limits l Number of failing SNP is indicator of genotype quality l Target fewer than 10 SNP in each category

12. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (12) Before clustering adjustment 86% call rate

13. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (13) After clustering adjustment 100% call rate

14. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (14) Parentage validation and discovery l Parent-progeny conflicts detected w Animal checked against all other genotypes w Reported to breeds and requesters w Correct sire usually detected l Maternal Grandsire checking w SNP at a time checking w Haplotype checking more accurate l Breeds moving to accept SNP in place of microsatellites

15. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (15) Checking facility l Labs place genotype files on AIPL server l Genotypes run through analysis procedures, but not added to database l Reports on missing nominations and QC data returned to Lab l Lab can w Detect sample misidentification w Improve clustering w Applying the same checks used by AIPL

16. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (16) Imputation l Based on splitting the genotype into individual chromosomes (maternal & paternal contributions) l Missing SNP assigned by tracking inheritance from ancestors and descendents l Imputed dams increase predictor population l 3K, LD, & 50K genotypes merged by imputing SNP not on LD or 3K

17. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (17) Data and evaluation flow Genomic Evaluation Lab Requester (Ex: AI, breeds) Dairy producers DNA laboratories samples genotypes nominations evaluations

18. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (18) Collaboration l Full sharing of genotypes with Canada w CDN calculates genomic evaluations on Canadian base l Trading of Brown Swiss genotypes with Switzerland, Germany, and Austria w Interbull may facilitate sharing l Agreements with Italy and Great Britain provide genotypes for Holstein w Negotiations underway with other countries

19. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (19) Genotyped Holsteins Date Young animals** All animals Bulls*Cows* Bulls Heifers 04-10 9,770 7,415 16,007 8,630 41,822 08-1010,430 9,37218,65211,021 49,475 12-1011,29312,82521,16118,336 63,615 01-1111,19413,58222,56722,999 70,342 02-1111,19613,93523,33026,270 74,731 03-1111,71314,38224,50529,929 80,529 04-1112,15211,22425,20236,545 85,123 05-1112,42911,83426,13940,996 91,398 06-1115,37912,09827,50845,632100,617 07-1115,38612,21928,45650,179106,240 08-1116,51914,38029,09052,053112,042 09-1116,81214,41530,18556,559117,971 *Traditional evaluation **No traditional evaluation

20. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (20) Calculation of genomic evaluations l Deregressed values derived from traditional evaluations of predictor animals l Allele substitutions random effects estimated for 45,187 SNP l Polygenic effect estimated for genetic variation not captured by SNP l Selection Index combination of genomic and traditional not included in genomic l Applied to yield, fitness, calving and type traits

21. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (21) Holstein prediction accuracy 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.

22. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (22) 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

23. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (23) Holstein Protein SNP Effects

24. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (24) Use of genomic evaluations l Determine which young bulls to bring into AI service l Use to select mating sires l Pick bull dams l Market semen from 2-year-old bulls

25. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (25) Use of LD genomic evaluations l Sort heifers for breeding w Flush w Sexed semen w Beef bull l Confirm parentage to avoid inbreeding l Predict inbreeding depression better l Precision mating considering genomics (future)

26. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (26) Ways to increase accuracy l Automatic addition of traditional evaluations of genotyped bulls when reach 5 years of age l Possible genotyping of 10,000 bulls with semen in CDDR l Collaboration with more countries l Use of more SNP from HD chips l Full sequencing

27. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (27) Application to more traits l Animal’s genotype is good for all traits l Traditional evaluations required for accurate estimates of SNP effects l Traditional evaluations not currently available for heat tolerance or feed efficiency l Research populations could provide data for traits that are expensive to measure l Will resulting evaluations work in target population?

28. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (28) Impact on producers l Young-bull evaluations with accuracy of early 1st­crop evaluations l AI organizations marketing genomically evaluated 2- year-olds l Genotype usually required for cow to be bull dam l Rate of genetic improvement likely to increase by up to 50% l Studs reducing progeny-test programs

29. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (29) Why Genomics works in Dairy l Extensive historical data available l Well developed genetic evaluation program l Widespread use of AI sires l Progeny test programs l High valued animals, worth the cost of genotyping l Long generation interval which can be reduced substantially by genomics

30. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (30) Summary l Extraordinarily rapid implementation of genomic evaluations l Chips provide genotypes of high accuracy l Comprehensive checking insures quality of genotypes stored l Young-bull acquisition and marketing now based on genomic evaluations l Genotyping of many females because of Low density chips

31. G.R. Wiggans 2011 DNA LandMarks User Group Meeting- Oct, 2011 (31)