Why genomics works and what is coming

1. Why genomics works and what is coming

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

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

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

5. Source of genomic evaluations • DNA extracted from blood, hair, or semen • 43,385 SNPs evaluated • SNP effect is difference in PTA from having 1 more A (BB v AB or AB v AA) • Genomic evaluation combines SNP effect estimates with existing parent average (PA) or PTA

6. Genotyping preparation • Nominate animal for genotyping • Collect hair, blood, or semen from animal • Blood may not be suitable for twins • Send to laboratory for DNA extraction • Transfer DNA to BeadChip (12 samples/chip) for 3-day genotyping process

7. Genotyping • Read red/green intensities from chip • Call genotypes from intensity file • Check genotypes: • Duplicates • Parent-progeny conflicts • Wrong Breed • Wrong sex

8. Clustering adjustment … before 86% call rate

9. Clustering adjustment … after 100% call rate

10. Genotype for Elevation • Chromosome 1 10001112200200121110111121111011110011211000201220022201111202101200211122110021112001111001011011010220011002201101120020110102022212112210201001110001122022122211202112012020100202202000021100011202011221112111022011110000212202000221012020002211220111012100111211102112110020102100022000220100020110000220221102211210112111012222001211212220020002002020201222110022222220022121111210021111200110111011200202220001112011010211121211102022100211201211001111102111211021112200010110111020220022111010201112111101120210210212110110221220012110112110120220110022200210021100011100211021101110002220020221212110002220102002222121221121112002011020200122222211221202121121011001211011020022000200100200011110110012110212121112010101212022101010111110211021122111111212111210110120011111021111011111220121012121101022202021211222120222002121210121210201100111222121101

11. Double grandson of Aerostar Genotype for inbred bull (Megastar) • Chromosome 24 102122210102102101110211011211221121100220200022202000202022000002200202222022020000200202222220000202222000002202000020022002000000222200022220000000000020222022002000222020222220002202222222220000200220202220200020002200000000220222000000220020200022220020200200202022202222222202220200020220220222202022202020202200022002220220022200000220200002002002000200222220002222020200222002220200002020000002222202020000200200222200020220222200220002222022002222020200022022022220022200220002002202000002200220222000022000022000222202002222000220020020202202000222000222002220220220000022022002002002022000200022220220022200202202002222022200000202200020200202020002200220000022022200202220200022002000200022002002000200220222220022022000200002000200002022002022020020000222000022200200020022200002202200200220022022020202020202000222020002202002022022202200002020200002020200022222200222200020022022220000020220020200202022022020200002000200220220002200

12. What can go wrong • Sample does not provide adequate DNA quality or quantity • Genotype has many SNPs that can’t be determined (90% call rate required) • Parent-progeny conflicts • Pedigree error • Sample ID error • Laboratory error • Unrelated animal qualifies as parent or progeny

13. Parent-progeny conflict • Parent 10212002101201211001020120100 • Progeny 10202010100200221001120120220

14. X chromosome • Bull 202220200002022220002020222020202 • Cow 120120121222201011102221021021202

15. Data & evaluation flow AI organizations, breed associations nominations samples evaluations Animal Improvement Programs Laboratory, USDA Dairy producers samples samples genotypes DNA laboratories

16. Protein PTA

17. Protein reliability

18. Reliabilities for young bulls Traditional PA Genomic PTA

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

20. Use of genomic evaluations • Determine which young bulls to bring into AI • Aid in selection of mating sires • Increasing impact on bull dam selection • Market semen from 2-year-old bulls

21. Updates between official evaluations • Genomic evaluations calculated every 2 months • Not released for animals that already have an official evaluation • Evaluations of new animals distributed to owners • Females by breed associations • Males by NAAB • Usually 2,000 new genotypes included

22. Impact on producers • Young-bull evaluations with accuracy of early 1st-crop evaluations • AI organizations marketing genomically evaluated 2-year-olds • Bull dams likely to be required to be genotyped • Rate of genetic improvement likely to increase by up to 50% • Progeny-test programs changing

23. International implications • All major dairy countries investigating genomic selection • Interbull working on how genomic evaluations should be integrated • Collaboration within Europe to share genotypes • Prediction accuracy continues to increase with increasing numbers of predictor animals • Importing countries must change rules to allow for genomically evaluated young bulls

24. Possible selection of embryos • In vitro fertilization of embryos from immature animals • Further reduces generation interval • Not yet feasible • Frozen, genotyped embryo market • Cost of genotyping < cost of ET • Could replace AI if accuracy high

25. Best chromosome 1 Co-Op Boliver Lisha-ET

26. Best chromosome 2 Kellercrest Earnit Hank

27. Best 30 chromosomes Genomics Extraordinare Overall net merit = $3,148

28. What may be coming • Approximate (impute) genotypes of missing ancestors to increase predictor population • Increase number of SNPs or even use entire DNA sequence • Impute 600K SNP from current 50K chip • Impute 50K from lower cost, lower density chip

29. Application to more traits • Animal’s genotype good for all traits • Traditional evaluations required for accurate estimation of SNP effects • Traditional evaluations not currently available for heat tolerance • Research populations could provide data for traits that are expensive to measure • Estimates of SNP effects must be appropriate for target population

30. Implications • Extraordinarily rapid implementation of genomic evaluations • Young-bull acquisition and marketing now based on genomic evaluations • Genomic evaluations may allow more cows from commercial herds to be used as bull dams

31. Financial support • National Research Initiative grants, USDA • 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) • Holstein Association USA (Brattleboro, VT) • American Jersey Cattle Association (Reynoldsburg, OH) • American Brown Swiss Association (Beloit, WI) • Agricultural Research Service, USDA