Biological Insights Gained from Genomic Prediction

1. Biological Insights Gained from Genomic Prediction

2. 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

3. What is a SNP? • Location on a chromosome at which nucleotides differ among animals • Usually not a quantitative trait locus (QTL) • With enough SNP, association between SNP and QTL alleles allows useful genetic evaluation • SNP chosen to be distributed evenly and have both alleles well represented in the population

4. Source of genomic evaluations • DNA is extracted from blood, hair, or semen • 43,385 SNP are 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

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

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

7. Clustering

8. Genotype for Elevation Chromosome 1 10001112200200121110111121111011110011211000201220022201111202101200211122110021112001111001011011010220011002201101120020110102022212112210201001110001122022122211202112012020100202202000021100011202011221112111022011110000212202000221012020002211220111012100111211102112110020102100022000220100020110000220221102211210112111012222001211212220020002002020201222110022222220022121111210021111200110111011200202220001112011010211121211102022100211201211001111102111211021112200010110111020220022111010201112111101120210210212110110221220012110112110120220110022200210021100011100211021101110002220020221212110002220102002222121221121112002011020200122222211221202121121011001211011020022000200100200011110110012110212121112010101212022101010111110211021122111111212111210110120011111021111011111220121012121101022202021211222120222002121210121210201100111222121101

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

10. What can go wrong? • Inadequate DNA quality or quantity • Genotype has many SNP that can’t be determined (90% call rate required) • Conflicts between parents and progeny • Pedigree error • Sample ID error • Laboratory error • An unrelated animal qualifies as parent or progeny

11. Parent-progeny conflict • Parent 10212002101201211001020120100 • Progeny 10202010100200221001120120220 • The two genotypes are inconsistent because parents and offspring can’t be homozygous for different alleles at the same locus

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

13. Genotyped animals (n=6,005)In North America as of April 2008

14. Genotyped animals (n=19,464)In North America as of December 2008

15. Genotyped animals (n=29,313)In North America as of June 2009

16. Reliability testHolstein, Jersey, and Brown Swiss breeds Data from 2004 used to predict independent data from 2009

17. Reliability gain1 for young bulls (Yield) 1Gain above parent average reliability of ~35%

18. Reliability gain for young bulls (Non-yield)

19. Reliability frequency

20. Protein PTA

21. Protein reliability

22. Adoption of genomic testingUS young bulls with NAAB codes, Apr 2009 * 2007-2008 counts are incomplete

23. Actual results from 50K chip • High correlation between genomic merit in November 2004 and August 2009 merit that includes performance data • 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

24. 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

25. 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

26. 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

27. International implications • All major dairy countries investigating genomic selection • Interbull researching how to integrate genomic evaluations • European collaboration 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

28. 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 and vitality not affected

29. Net merit by chromosome Freddie (1HO08784) - high Net Merit bull

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

31. Best chromosome 2 Kellercrest Earnit Hank

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

33. Finding QTL quickly and easily

34. Locating autosomal recessives

35. Relationships among genotyped Holsteins

36. Interbreed relationships

37. Closing thoughts • 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 • SNP data are valuable tools for basic research

38. Acknowledgments • Genotyping and DNA extraction: • BFGL, U. Missouri, U. Alberta, GeneSeek, Genetics & IVF Institute, Genetic Visions, and Illumina • Computing: • AIPL staff (Leigh Walton, Jay Megonigal) • Funding: • NRI grants 2006-35205-16888 and 2006-35205-16701 • Agriculture Research Service • Holstein, Jersey and Brown Swiss breed associations • Cooperative Dairy DNA Repository (CDDR)

39. CDDR contributors • National Association of Animal Breeders (Columbia, MO) • ABS Global (DeForest, WI) • Accelerated Genetics (Baraboo, WI) • Alta (Balzac, AB, Canada) • Genex (Shawano, WI) • New Generation Genetics (Fort Atkinson, WI) • Select Sires (Plain City, OH) • Semex Alliance (Guelph, ON, Canada) • Taurus-Service (Mehoopany, PA)