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North American Cooperation in Genomic Prediction

North American Cooperation in Genomic Prediction. Sequencing and Genotyping. Cattle genome sequenced in 2004 30 chromosome pairs (including X,Y) 3 billion letters from each parent Illumina BovineSNP50 BeadChip 58,000 genetic markers in 2007 38,416 used in genomic predictions

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North American Cooperation in Genomic Prediction

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  1. North American Cooperation in Genomic Prediction

  2. Sequencing and Genotyping • Cattle genome sequenced in 2004 • 30 chromosome pairs (including X,Y) • 3 billion letters from each parent • Illumina BovineSNP50 BeadChip • 58,000 genetic markers in 2007 • 38,416 used in genomic predictions • Current cost <$250 per animal

  3. History of Genomic Cooperation • 1992 USDA request for CAN, USA AI companies to join Dairy Bull DNA Repository maintained at U. Illinois • CIAQ (Brian Van Doormaal) provided 1110 straws from 110 bulls • 1999 Cooperative Dairy DNA Repository maintained at Beltsville, MD • Semex and Alta contributed semen for all progeny tested bulls

  4. CDDR Contributors • National Association of Animal Breeders (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)

  5. Genotype Data for ElevationChromosome 1 1000111220020012111011112111101111001121100020122002220111 1202101200211122110021112001111001011011010220011002201101 1200201101020222121122102010011100011220221222112021120120 2010020220200002110001120201122111211102201111000021220200 0221012020002211220111012100111211102112110020102100022000 2201000201100002202211022112101121110122220012112122200200 0200202020122211002222222002212111121002111120011011101120 0202220001112011010211121211102022100211201211001111102111 2110211122000101101110202200221110102011121111011202102102 1211011022122001211011211012022011002220021002110001110021 1021101110002220020221212110002220102002222121221121112002 0110202001222222112212021211210110012110110200220002001002 0001111011001211021212111201010121202210101011111021102112 2111111212111210110120011111021111011111220121012121101022 202021211222120222002121210121210201100111222121101

  6. Genotype Data from Inbred BullChromosome 24 of Megastar 1021222101021021011102110112112211211002202000222020002020220 0000220020222202202000020020222222000020222200000220200002002 2002000000222200022220000000000020222022002000222020222220002 2022222222200002002202022202000200022000000002202220000002200 2020002222002020020020202220222222220222020002022022022220202 2202020202200022002220220022200000220200002002002000200222220 0022220202002220022202000020200000022222020200002002002222000 2022022220022000222202200222202020002202202222002220022000200 2202000002200220222000022000022000222202002222000220020020202 2020002220002220022202202200000220220020020020220002000222202 2002220020220200222202220000020220002020020202000220022000002 2022200202220200022002000200022002002000200220222220022022000 2000020002000020220020220200200002220000222002000200222000022 0220020022002202202020202020200022202000220200202202220220000 2020200002020200022222200222200020022022220000020220020200202 022022020200002000200220220002200

  7. Close Inbreeding (F=14.7%): Double Grandson of Aerostar Aerostar Megastar Aerostar Chromosome 24

  8. Holstein Experimental Design • Compute genomic evaluations and parent averages from 2003 data • 3576 older Holstein bulls born 1952-1998 • Compare ability to predict daughter deviations in 2008 data • 1759 younger bulls born 1999-2002 • Test results for 27 traits: 5 yield, 5 health, 16 conformation, and Net Merit

  9. Genotyped Holsteins (n=6005)As of April 2008

  10. Jersey and Brown Swiss • Jersey experimental design • Data from 579 bulls born before 1999 and 204 cows with data before 2003 • Predict 352 bulls born during or after 1999 • Brown Swiss experimental design • Data from 225 bulls born before 1999 • Predict 118 bulls born during or after 1999

  11. Genomic Methods • Direct genomic evaluation • Evaluate genotyped animals by summing effects of 38,416 genetic markers (SNPs) • Combined genomic evaluation • Include phenotypes of nongenotyped ancestors by selection index • Transferred genomic evaluation • Propagate info from genotyped animals to nongenotyped relatives (not done yet)

  12. Significance Tests for Net Merit

  13. Marker Effects for Net Merit

  14. Major Gene on Chromosome 18Net Merit, Productive Life, Calving Ease, Stature, Strength, Rump Width

  15. Marker Effects for Milk

  16. Marker Effects for Final Score

  17. Reliability Gain by Breed

  18. Reliability Gain by Breed

  19. Reliability Gains for Proven Bulls • Proven bulls included in test had: • >10 daughters in August 2003 • >10% increase in reliability by 2008 • Numbers of bulls in test ranged from 104 to 735 across traits • Predicted the change in evaluation • Significant increase in R2 (P < .001) for 26 of 27 traits

  20. Net Merit by Chromosome for O ManTop bull for Net Merit

  21. SNPs on X Chromosome • Each animal has two evaluations: • Expected genetic merit of daughters • Expected genetic merit of sons • Difference is sum of effects on X • SD = .1 σG, smaller than expected • Correlation with sire’s daughter vs. son PTA difference was significant (P<.0001), regression close to 1.0

  22. X, Y, Pseudo-autosomal SNPs 35 SNPs 35 SNPs 0 SNPs 487 SNPs

  23. Clones and Identical Twins21HO2121, 21HO2125, 21HO2100, CAN6139300, CAN6139303

  24. Value of Genotyping More SNP9,604 (10K), 19,208 (20K), and 38,416 (40K) SNP

  25. Value of Genotyping More Bulls

  26. Simulated ResultsWorld Holstein Population • 15,197 older and 5,987 younger bulls in Interbull file • 40,000 SNPs and 10,000 QTLs • Provided timing, memory test • Reliability vs parent average REL • REL = corr2 (EBV, true BV) • 80% vs 34% expected for young bulls • 72% vs 30% observed in simulation

  27. Expected vs Observed ReliabilityHolsteins • Reliability for predictee bulls • Traditional PA: 27% average across traits • Genomic: 63% expected vs. 50% observed • Observed range 78% (fat pct) to 31% (SCE) • PTA regressions .8 to .9 of expected • Multiply genomic daughter equivalents by .7 to make expected closer to observed • For example, 16 * .7 = 11 • Include polygenic effect, less than 5%

  28. Genetic ProgressHolsteins • Assume 60% REL for net merit • Sires mostly 2 instead of 6 years old • Dams of sons mostly heifers with 60% REL instead of cows with phenotype and genotype (66% REL) • Progress could increase by >50% • 0.37 vs. 0.23 genetic SD per year • Reduce generation interval more than accuracy

  29. Genetic Evaluation Advancesand increases in genetic progress

  30. Genetic Evaluation Timing • CAN, USA had same genetic evaluation schedule since early 1980’s • Same with 2X, 4X, and 3X releases per year • Files exchanged 1 week before a combined release, 1993-1996 • Interbull evaluations began in 1995 • MACE methods developed in CAN • Correlation estimation programs from USA • First director: PhD in USA, post-doc in CAN • MACE conformation by N.A. Consortium

  31. CAN, USA Combined Data • Evaluations tested and reported in 1991 • Banos and Wiggans, Robinson and Wiggans, Powell et al, Wiggans et al • Both countries used Cornell computer • Animal models applied to yield data of Jerseys and Ayrshires • Correlations .98 and .96 between combined vs. converted evaluation

  32. Conclusions • Genomic predictions significantly better than parent average (P < .0001) for all 26 traits tested • High reliability requires many genotypes and phenotypes • Close cooperation between CAN and USA will continue • Science, software, and data sharing

  33. Acknowledgments • Genotyping and DNA extraction: • BFGL, U. Missouri, U. Alberta, GeneSeek, GIFV, and Illumina • Computing: • AIPL staff (Mel Tooker, Leigh Walton, etc.) • Funding: • National Research Initiative grants • 2006-35205-16888, 2006-35205-16701 • Agriculture Research Service • Contributors to Cooperative Dairy DNA Repository (CDDR)

  34. CDDR Contributors • National Association of Animal Breeders (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)

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