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2007 Paul VanRaden, Mel Tooker, and Nicolas Gengler Animal Improvement Programs Lab, Beltsville, MD, USA, and Gembloux Agricultural U., Belgium Paul.VanRaden@ars.usda.gov 2008 Effects of Allele Frequency Estimation on Genomic Predictions and Inbreeding Coefficients
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FASS annual meeting, July 2008 (2) Mel Tooker 2008 Experimental Design Predict April 2008 PTA from August 2003 PTA 3,576 older Holstein bulls 1,759 younger bulls (total = 5,335) Using 38,416 SNP from Illumina Bovine SNP50 TM Chip
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FASS annual meeting, July 2008 (3) Mel Tooker 2008 Goals Compare genomic to traditional relationships and inbreeding Formulas to compute G and A G – A differences for 5,335 bulls Compare genomic predictions using different estimates of frequency Estimate 38,416 allele frequencies Simple estimates vs. base population Or ignore frequency, use 0.5 instead
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FASS annual meeting, July 2008 (4) Mel Tooker 2008 Differences in G and A 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
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FASS annual meeting, July 2008 (5) Mel Tooker 2008 Genotype Data for Elevation Chromosome 1 1000111220020012111011112111101111001121100020122002220111 1202101200211122110021112001111001011011010220011002201101 1200201101020222121122102010011100011220221222112021120120 2010020220200002110001120201122111211102201111000021220200 0221012020002211220111012100111211102112110020102100022000 2201000201100002202211022112101121110122220012112122200200 0200202020122211002222222002212111121002111120011011101120 0202220001112011010211121211102022100211201211001111102111 2110211122000101101110202200221110102011121111011202102102 1211011022122001211011211012022011002220021002110001110021 1021101110002220020221212110002220102002222121221121112002 0110202001222222112212021211210110012110110200220002001002 0001111011001211021212111201010121202210101011111021102112 2111111212111210110120011111021111011111220121012121101022 202021211222120222002121210121210201100111222121101
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FASS annual meeting, July 2008 (6) Mel Tooker 2008 Genotype Data from Inbred Bull Chromosome 24 of Megastar 1021222101021021011102110112112211211002202000222020002020220 0000220020222202202000020020222222000020222200000220200002002 2002000000222200022220000000000020222022002000222020222220002 2022222222200002002202022202000200022000000002202220000002200 2020002222002020020020202220222222220222020002022022022220202 2202020202200022002220220022200000220200002002002000200222220 0022220202002220022202000020200000022222020200002002002222000 2022022220022000222202200222202020002202202222002220022000200 2202000002200220222000022000022000222202002222000220020020202 2020002220002220022202202200000220220020020020220002000222202 2002220020220200222202220000020220002020020202000220022000002 2022200202220200022002000200022002002000200220222220022022000 2000020002000020220020220200200002220000222002000200222000022 0220020022002202202020202020200022202000220200202202220220000 2020200002020200022222200222200020022022220000020220020200202 022022020200002000200220220002200
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FASS annual meeting, July 2008 (7) Mel Tooker 2008 Close Inbreeding (F=14.7%): Double Grandson of Aerostar Aerostar Megastar Chromosome 24
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FASS annual meeting, July 2008 (8) Mel Tooker 2008 3 Formulas to Compute G Sum products of genotypes (g) adjusted for allele frequency (p) G1 jk = ∑ (g ij -p i ) (g ik -p i ) / [2 ∑ p i (1-p i )] Or individually weighted by p G2 jk = ∑ (g ij -p i ) (g ik -p i ) / 2p i (1-p i ) Or scaled by intercept (b 0 ) and regression (b 1 ) on A, using p = 0.5 G3 jk = [∑ (g ij - 0.5) (g ik - 0.5) – b 0 ] / b 1
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FASS annual meeting, July 2008 (9) Mel Tooker 2008 Compare A with 3 formulas for G Simulated Data Diagonals 1 of G FormulaMeanSDCorr. with A A1.05.0231.00 G10.95.0310.60 G20.88.0280.54 G31.10.0360.66 1 Diagonal = 1 + Inbreeding
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FASS annual meeting, July 2008 (10) Mel Tooker 2008 Compare A with 3 formulas for G Actual Data Diagonals 1 of G FormulaMeanSDCorr. with A A1.05.0231.00 G11.00.0310.68 G20.98.0310.69 G31.13.0350.63 1 Diagonal = 1 + Inbreeding
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FASS annual meeting, July 2008 (11) Mel Tooker 2008 Summary of G Formulas for Genomic Inbreeding Correlations ranked G3 > G1 > G2 in simulation vs. G2 > G1 > G3 with real data (opposite) G2 and G1 biased down, G3 up G1 and G2 can be adjusted toward A using b 0 and b 1, similar to G3 formula After adjusting, mean G1 = 1.08 and G2 = 1.09 compared to G3 = 1.13 and A = 1.05 G1 was unbiased in simulation using true rather than estimated frequencies
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FASS annual meeting, July 2008 (12) Mel Tooker 2008 Allele Frequency Estimation Base population frequencies Combine genotypes and pedigrees Efficient algorithm (Gengler, 2007) Simple frequency estimates p i = ∑ g ij / 2n Extra simple estimates (p = 0.5) Z = 0.5, 0, -0.5 in mixed model
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FASS annual meeting, July 2008 (13) Mel Tooker 2008 Effects of Frequency on G1 Frequency Estimate Mean of Diagonal Corr (G1, A) DiagonalOff-diag Base1.00.68.86 Simple1.00.32.75.51.26.63.83
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FASS annual meeting, July 2008 (14) Mel Tooker 2008 R 2 of Genomic Predictions Frequency estimates Trait.5SimpleBase Net Merit.276.278.284 Milk.467.480.485 Protein yield.468.469.470 Fat %.586.632.633 Productive life.248.263.274 Somatic cell score.369.375.383 Dtr pregnancy rate.283.284.290
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FASS annual meeting, July 2008 (15) Mel Tooker 2008 Conclusions Genomic relationships and inbreeding are more useful than Wright’s 1922 pedigree formulas Formulas to compute G have Large effects on inbreeding coefficients Small effects on reliability of predictions Estimates of allele frequencies For base population better than simple Not needed using regression of G on A
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FASS annual meeting, July 2008 (16) Mel Tooker 2008 Acknowledgments Funding: National Research Initiative grants CDDR Contributors (NAAB, Semex) Genotyping and DNA extraction: BFGL, U. Missouri, U. Alberta, GeneSeek, GIFV, and Illumina Computing from AIPL staff George Wiggans, Leigh Walton
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