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Genomics for Emerging Markets . Proven Bulls or Emerging Bulls?. Genetic Terms. Predicted transmitting ability and parent average PTA required progeny or own records PA included only parent data Genomics provides more information Reliability = Corr 2 (predicted, true TA)
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Genetic Terms • Predicted transmitting ability and parent average • PTA required progeny or own records • PA included only parent data • Genomics provides more information • Reliability = Corr2(predicted, true TA) • Reliability of PA could not exceed 50% because of Mendelian sampling • Genomics can predict the other 50% • Reliability limit at birth theoretically 99%
New Genetic Terms • Genomic vs. pedigree relationships • Expected genes in common (A) • Actual genes in common (G) • Several formulas to compute G • Genomic vs. pedigree inbreeding • Correlated by 0.68 in Holstein • Correlated by 0.80 in Angus • Daughter merit vs. son merit (X vs. Y)
Differences in G and AG = genomic and A = pedigree relationships • Detected clones, identical twins, and duplicate samples • Detected incorrect DNA samples • Detected incorrect pedigrees • Identified correct source of DNA by genomic relationships with other animals
Genomic vs. PedigreeInbreeding Correlation = .68
Phenotypic Data • 26 traits plus the Net Merit index • The 6,184 bulls genotyped have >10 million phenotyped daughters (average 2,000 daughters per bull) • Most traits recorded uniformly across the world • Foreign data provided by Interbull
Repeatability of Genotypes • 2 laboratories genotyped the same 46 bulls • About 1% missing genotypes per lab • Mean of 98% SNP same (37,624 out of 38,416) • Range across animals of 20 to 2,244 SNP missing • Mean of 99.997% SNP concordance (conflict <0.003%) • Mean of 0.9 errors per 38,416 SNP • Range across animals of 0 to 7 SNP conflicts
Genomic Methods • Direct genomic evaluation • Sum of effects for 38,416 genetic markers • Not published • Combined genomic evaluation • Include phenotypes of non-genotyped ancestors by selection index • Transferred genomic evaluation • Propagate info from genotyped animals to non-genotyped relatives by selection index
Genotyped Animals (n=22,344)In North America as of February 2009
Experimental Design - UpdateHolstein, Jersey, and Brown Swiss breeds Data from 2004 used to predict independent data from 2009
Reliability Gain1 by BreedYield traits and NM$ of young bulls 1Gain above parent average reliability ~35%
Reliability Gain by BreedHealth and type traits of young bulls
Value of Genotyping More AnimalsActual and predicted gains for 27 traits and for Net Merit Cows: 947 1916
USA Evaluation • Genomic PTAs official in January • Traditional PTAs sent to Interbull • MACE used if foreign dtrs included • Genomic info used for most bulls • Genomic PTA transferred to descendants (to ancestors in future) • Jersey results also are official • More Brown Swiss needed (CHE)
Net Merit of Top 20 Bulls from 2009 data based on selection in 2004
Average regressions across all traits Predict 2009 from 2004 data, expected = 1.00
Net Merit regressions Predict 2009 from 2004 data, expected = 1.00
Adoption of Genomic TestingUS young bulls purchased by AI companies * 2007-2008 counts are incomplete
Genetic Progress • Assume 60% REL for net merit • Sires mostly 1-3 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
Worldwide Dairy Genotypingas of January 2009 1Using a customized Illumina 50K chip (different markers)
North American Cooperation • 174 markers, 1068 USA and CAN bulls • Illinois, Israel, and USDA researchers • 1991-1999 • 367 markers, 1415 USA and CAN bulls • USDA, Illinois, and Israel • 1995-2004 • 38,416 markers, 22,344 animals • USDA, Missouri, Canada, and Illumina • Oct 2007- Dec 2008
Foreign DNA in North American DataProven bulls, Young bulls, and Females
Country Borders • Most phenotypic data collected and stored within country • Genomic data allows simple, accurate prediction across borders • Need traditional EBV or PA for foreign animals, but not available for young bulls, cows, or heifers • May need full foreign pedigrees • Genomic evaluations official on USA scale for many foreign animals (not just CAN)
Simulation ResultsWorld Holstein Population • 40,360 older bulls to predict 9,850younger bulls in Interbull file • 50,000 or 100,000 SNP; 5,000 QTL • Reliability vs. parent average REL • Genomic REL = corr2 (EBV, true BV) • 81% vs 30% observed using 50K • 83% vs 30% observed using 100K
Cooperative International Projects • Traditional genetic evaluations • MACE instead of merging phenotypes • Small benefits expected from data merger • Proven bulls only, not cows or young bulls • Parentage testing, genetic recessives, pedigrees done by breed associations • Genomics: what role for Interbull? • Benefits of sharing genotypes are large
Genotype Exchange Options • Give away for free (not likely) • Genotype own bulls, then trade? • Trade an equal number or all bulls? • Country A has 5000 and B has 1000 • Proportional to population size? • Trade among organization pairs or create central genomic database? • Service fee for young animals to pay for ancestor genotyping?
Problems of Not Sharing • Genetic progress not as fast as with full access to genotypes • Severe limits on researcher access to genotypes (secrecy) • Genomics may lead to natural monopoly, similar to railroads • Small companies / countries can’t afford to buy sufficient genotypes
Low Density SNP Chip • Choose 384 marker subset • SNP that best predict net merit • Parentage markers to be shared • Use for initial screening of cows • 40% benefit of full set for 10% cost • Could get larger benefits using haplotyping (Habier et al., 2008)
Insignificant SNP Effects • Traditional selection on PA • 50 : 50 chance of better chromosome • 1 SNP with tiny effect • 50.01 : 49.99 chance • 38,416 SNPs with tiny effects • 70 : 30 chance • Only test overall sum of effects!
Conclusions - 1 • High accuracy requires very many genotypes and phenotypes • 100X more markers allows MAS across rather than within families • 5X more bulls allows estimation of much smaller QTL effects (HO) • Most traits are very quantitative (few major genes)
Conclusions - 2 • Reliability increases by tracing actual genes inherited instead of expected average from parents • Genomic reliability > traditional • 30-40% with traditional parent average • 60-70% using 8,100 genotyped Holsteins • 81-83% from 40,000 simulated bulls • Gains much smaller for USA JER and BSW breeds • Trading, sharing, profit is needed
Acknowledgments • Genotyping and DNA extraction: • USDA Bovine Functional Genomics Lab, U. Missouri, U. Alberta, GeneSeek, Genetics & IVF Institute, Genetic Visions, and Illumina • Computing: • AIPL staff (Mel Tooker, Leigh Walton, Jay Megonigal) • Funding: • National Research Initiative grants • 2006-35205-16888, 2006-35205-16701 • Agriculture Research Service • Holstein and Jersey breed associations • Contributors to Cooperative Dairy DNA Repository (CDDR)
CDDR Contributors • National Association of Animal Breeders (NAAB, 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)