1. G.R. Wiggans Animal Improvement Programs Laboratory Agricultural Research Service, USDA Beltsville, MD george.wiggans@ars.usda.gov G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (1) Why genomics works and what is coming

2. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (2) What is genomics? l Study of the effects of an animal’s genes l Evaluations are based on DNA markers l Single-nucleotide polymorphism (SNP) markers are abundant and cheap to read l Illumina BovineSNP50 BeadChip provides genotypes for >50,000 (50K) SNP l Possible genotypes across 2 chromosomes at each SNP are AA, AB, and BB

3. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (3) What is whole-genome selection? l Many markers used to track inheritance of chromosomal segments l Impact of each segment estimated for each trait l Estimates combined with traditional predicted transmitting ability (PTA) to produce genomic evaluation (GPTA) l Animals can be selected shortly after birth

4. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (4) What is a SNP? l Place on the chromosome where animals differ in their DNA nucleotides (A, C, T, or G) l Usually not part of the gene that controls a trait – quantitative trait locus (QTL) l With enough SNPs, association between SNP and QTL alleles allows useful genetic evaluation l SNPs chosen to be distributed evenly and have both alleles well represented in the population

5. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (5) Source of genomic evaluations l DNA extracted from blood, hair, or semen l 43,385 SNPs evaluated l SNP effect is difference in PTA from having 1 more A (BB v AB or AB v AA) l Genomic evaluation combines SNP effect estimates with existing parent average (PA) or PTA

6. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (6) Genotyping preparation l Nominate animal for genotyping l Collect hair, blood, or semen from animal w Blood may not be suitable for twins l Send to laboratory for DNA extraction l Transfer DNA to BeadChip (12 samples/chip) for 3-day genotyping process

7. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (7) Genotyping l Read red/green intensities from chip l Call genotypes from intensity file l Check genotypes: w Duplicates w Parent-progeny conflicts w Wrong Breed w Wrong sex

8. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (8) Clustering adjustment … before 86% call rate

9. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (9) Clustering adjustment … after 100% call rate

10. G.R. WiggansADSA 18 th DISCOVER Conference –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enotype for Elevation l Chromosome 1

11. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (11) 10212221010210210111021101121122112110022020002220 20002020220000022002022220220200002002022222200002 02222000002202000020022002000000222200022220000000 00002022202200200022202022222000220222222222000020 02202022202000200022000000002202220000002200202000 22220020200200202022202222222202220200020220220222 20202220202020220002200222022002220000022020000200 20020002002222200022220202002220022202000020200000 02222202020000200200222200020220222200220002222022 00222202020002202202222002220022000200220200000220 02202220000220000220002222020022220002200200202022 02000222000222002220220220000022022002002002022000 20002222022002220020220200222202220000020220002020 02020200022002200000220222002022202000220020002000 22002002000200220222220022022000200002000200002022 00202202002000022200002220020002002220000220220020 02200220220202020202020002220200022020020220222022 00002020200002020200022222200222200020022022220000 020220020200202022022020200002000200220220002200 Genotype for inbred bull (Megastar) l Chromosome 24 Double grandson of Aerostar

12. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (12) What can go wrong l Sample does not provide adequate DNA quality or quantity l Genotype has many SNPs that can’t be determined (90% call rate required) l Parent-progeny conflicts w Pedigree error w Sample ID error w Laboratory error w Unrelated animal qualifies as parent or progeny

13. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (13) Parent-progeny conflict l Parent 10212002101201211001020120100 l Progeny 10202010100200221001120120220

14. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (14) l Bull 202220200002022220002020222020202 l Cow 120120121222201011102221021021202 X chromosome

15. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (15) Data & evaluation flow Animal Improvement Programs Laboratory, USDA AI organizations, breed associations Dairy producers DNA laboratories samples genotypes nominations evaluations

16. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (16) Protein PTA

17. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (17) Protein reliability

18. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (18) Reliabilities for young bulls Genomic PTA Traditional PA

19. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (19) Actual results from 50K chip l High correlation between genomic merit in November 2004 and August 2009 merit that includes performance l Bull with highest genomic net merit in November 2004 (Man O Man) now ranks 4th of 1,925 bulls l Bull with highest genomic net merit in January 2009 (Freddie) now ranks 2nd

20. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (20) Use of genomic evaluations l Determine which young bulls to bring into AI l Aid in selection of mating sires l Increasing impact on bull dam selection l Market semen from 2-year-old bulls

21. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (21) Updates between official evaluations l Genomic evaluations calculated every 2 months l Not released for animals that already have an official evaluation l Evaluations of new animals distributed to owners w Females by breed associations w Males by NAAB l Usually 2,000 new genotypes included

22. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (22) Impact on producers l Young-bull evaluations with accuracy of early 1st- crop evaluations l AI organizations marketing genomically evaluated 2-year-olds l Bull dams likely to be required to be genotyped l Rate of genetic improvement likely to increase by up to 50% l Progeny-test programs changing

23. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (23) International implications l All major dairy countries investigating genomic selection l Interbull working on how genomic evaluations should be integrated l Collaboration within Europe to share genotypes l Prediction accuracy continues to increase with increasing numbers of predictor animals l Importing countries must change rules to allow for genomically evaluated young bulls

24. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (24) Possible selection of embryos l In vitro fertilization of embryos from immature animals w Further reduces generation interval w Not yet feasible l Frozen, genotyped embryo market w Cost of genotyping < cost of ET w Could replace AI if accuracy high

25. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (25) Best chromosome 1 Co-Op Boliver Lisha-ET

26. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (26) Best chromosome 2 Kellercrest Earnit Hank

27. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (27) Best 30 chromosomes Genomics Extraordinare Overall net merit = $3,148

28. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (28) What may be coming l Approximate (impute) genotypes of missing ancestors to increase predictor population l Increase number of SNPs or even use entire DNA sequence l Impute 600K SNP from current 50K chip l Impute 50K from lower cost, lower density chip

29. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (29) Application to more traits l Animal’s genotype good for all traits l Traditional evaluations required for accurate estimation of SNP effects l Traditional evaluations not currently available for heat tolerance l Research populations could provide data for traits that are expensive to measure w Estimates of SNP effects must be appropriate for target population

30. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (30) Implications l Extraordinarily rapid implementation of genomic evaluations l Young-bull acquisition and marketing now based on genomic evaluations l Genomic evaluations may allow more cows from commercial herds to be used as bull dams

31. G.R. WiggansADSA 18 th DISCOVER Conference – 2009 (31) Financial support l National Research Initiative grants, USDA l NAAB (Columbia, MO) w ABS Global (DeForest, WI) w Accelerated Genetics (Baraboo, WI) w Alta (Balzac, AB) w Genex (Shawano, WI) w New Generation Genetics (Fort Atkinson, WI) w Select Sires (Plain City, OH) w Semex Alliance (Guelph, ON) w Taurus-Service (Mehoopany, PA) l Holstein Association USA (Brattleboro, VT) l American Jersey Cattle Association (Reynoldsburg, OH) l American Brown Swiss Association (Beloit, WI) l Agricultural Research Service, USDA