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2007 Melvin Tooker Animal Improvement Programs Laboratory USDA Agricultural Research Service, Beltsville, MD, USA Melvin.Tooker@ars.usda.gov Melvin.Tooker@ars.usda.gov 2009 An Introduction to Genomics
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India Emerging Markets Conference, May 2009 (2) Melvin Tooker 2009 Genomic Goals Predict young bulls and cows more accurately Compare actual DNA inherited Use exact relationship matrix G instead of expected values in A Trace chromosome segments Locate genes with large effects
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India Emerging Markets Conference, May 2009 (3) Melvin Tooker 2009 Short history Illumina BovineSNP50™ BeadChip developed Accuracy of genomic information assessed by using 2004 evaluations of bulls born before 2000 to predict 2009 evaluations of young bulls Unofficial genomic evaluations of bull calves provided to industry beginning in April 2008 Jersey results released in October 2008 Over 23,000 animals genotyped through Mar. 2009
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India Emerging Markets Conference, May 2009 (4) Melvin Tooker 2009 Source of genomic evaluations DNA extracted from blood, hair, or semen ~40,000 genetic markers (SNPs) evaluated For each SNP, difference in PTA estimated between animals with 1 allele compared to the other allele Genomic data contribute ~11 daughter equivalents to reliability
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India Emerging Markets Conference, May 2009 (5) Melvin Tooker 2009 How Related are Relatives? Example: Full sibs are expected to share 50% of their DNA on average may actually share 45% or 55% of their DNA because each inherits a different mixture of chromosome segments from the two parents. Combine genotype and pedigree data to determine exact fractions
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India Emerging Markets Conference, May 2009 (6) Melvin Tooker 2009 Genomic Relationships Measures of genetic similarity A = Expected % genes identical by descent from pedigree (Wright, 1922) G = Actual % of DNA shared (using genotype data) T = % genes shared that affect a given trait (using genotype and phenotype)
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India Emerging Markets Conference, May 2009 (7) Melvin Tooker 2009 Markers vs QTLs Models contain markers, not QTLs M is markers inherited minus freq M M’ / ∑ p(1-p) = G List all QTL affecting a trait Q is alleles inherited minus freq q contains effects of alleles u = Q q, var(q) = V q var(u) = E(u u’) = Q V q Q’ = T
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India Emerging Markets Conference, May 2009 (8) Melvin Tooker 2009 QTL Relationship Matrix (T) Three bulls have +50 PTA protein. Do they have the same genes? Extremely unlikely. Bull A could have 10 positive genes. Bull B could have 10 positive genes, but on different chromosomes. Bull C could have 20 positive and 10 negative genes.
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India Emerging Markets Conference, May 2009 (9) Melvin Tooker 2009 Genes in Common at One Locus If Full Sib 1 inherits: If Full Sib 2 inherits: w,yw,zx,yx,z w,y2110 w,z1201 x,y1021 x,z0112 w = gene from sire of sire x = gene from dam of sire y = gene from sire of dam z = gene from dam of dam
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India Emerging Markets Conference, May 2009 (10) Melvin Tooker 2009 Unrelated Individuals? No known common ancestors Many unknown common ancestors born before the known pedigree Relationships in base 0 ± x.x% due to earlier ancestors Called linkage disequilibrium (LD) Poor terminology, genes may not be physically linked
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India Emerging Markets Conference, May 2009 (11) Melvin Tooker 2009 Traditional Pedigree Sire of Sire Sire Dam of Sire Animal Sire of Dam Dam Dam of Dam
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India Emerging Markets Conference, May 2009 (12) Melvin Tooker 2009 Genomic Pedigree
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India Emerging Markets Conference, May 2009 (13) Melvin Tooker 2009 Example of a SNP haplotype caacgtat caacggat SNP atccgaat atccgcat … …… … SNP tctaggat tctcggat SNP … …Chr1 Chr2 Haplotype is a set of single nucleotide polymorphisms (SNPs) associated on a single chromosome. Identification of a few alleles of a haplotype block can identify other polymorphic sites in the region. Haplotype 1tca gacHaplotype 2
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India Emerging Markets Conference, May 2009 (14) Melvin Tooker 2009 SNP Pedigree atagatcgatcg ctgtagcttagg agggcgcgcagt cgatctagatcg cggtagatcagt agagatcgatct atggcgcgaacg ctatcgctcagg ctgtagcgatcg agatctagatcg agagatcgcagt atgtcgctcacg ctgtctagatcg atgtcgcgcagt
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India Emerging Markets Conference, May 2009 (15) Melvin Tooker 2009 Haplotype Pedigree atagatcgatcg ctgtagcttagg agggcgcgcagt cgatctagatcg cggtagatcagt agagatcgatct atggcgcgaacg ctatcgctcagg ctgtagcgatcg agatctagatcg agagatcgcagt atgtcgctcacg ctgtctagatcg atgtcgcgcagt
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India Emerging Markets Conference, May 2009 (16) Melvin Tooker 2009 Translate Haplotype to Genotype agatctagatcg 111211120200 ctgtagcgatcg
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India Emerging Markets Conference, May 2009 (17) Melvin Tooker 2009 Genotype Pedigree Count number of second allele 121101011110 111211120200 101121101111 122221121111 101101111102 011111012011 121120011010 0 = homozygous for first allele (alphabetically) 1 = heterozygous 2 = homozygous for second allele (alphabetically)
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India Emerging Markets Conference, May 2009 (18) Melvin Tooker 2009 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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India Emerging Markets Conference, May 2009 (19) Melvin Tooker 2009 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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India Emerging Markets Conference, May 2009 (20) Melvin Tooker 2009 Genotype Parents and Grandparents Manfred O-Man Jezebel O-Style Teamster Deva Dima
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India Emerging Markets Conference, May 2009 (21) Melvin Tooker 2009 Expected Relationship Matrix 1 1HO9167 O-Style PGSPGDMGSMGDSireDamBull Manfred 1.0.0.5.0.25 Jezebel.01.0.0.5.0.25 Teamster.0 1.0. 0.5.25 Dima.0 1.0.0.5.25 O-Man.5.0 1.0.0.5 Deva.0.5.01.0.5 O-Style.25.5 1.0 1 Calculated assuming that all grandparents are unrelated
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India Emerging Markets Conference, May 2009 (22) Melvin Tooker 2009 Pedigree Relationship Matrix 1HO9167 O-Style PGSPGDMGSMGDSireDamBull Manfred 1.053.090.105.571.098.334 Jezebel.0901.037.051.099.563.075.319 Teamster.090.0511.035.120.071.578.324 Dima.105.099.1201.042.102.581.342 O-Man.571.563.071.1021.045.086.566 Deva.098.075.578.581.0861.060.573 O-Style.334.319.324.342.566.5731.043
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India Emerging Markets Conference, May 2009 (23) Melvin Tooker 2009 Genomic Relationship Matrix 1HO9167 O-Style PGSPGDMGSMGDSireDamBull Manfred 1.201.058.050.093.609.054.344 Jezebel.0581.131.008.135.618.079.357 Teamster.050.0081.110.100.014.613.292 Dima.093.135.1001.139.131.610.401 O-Man.609.618.014.1311.166.080.626 Deva.054.079.613.610.0801.148.613 O-Style.344.357.292.401.626.6131.157
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India Emerging Markets Conference, May 2009 (24) Melvin Tooker 2009 Difference (Genomic – Pedigree) 1HO9167 O-Style PGSPGDMGSMGDSireDamBull Manfred.149-.032-.040-.012.038-.043.010 Jezebel -.032.095-.043.036.055.004.038 Teamster -.040-.043.075-.021-.057.035-.032 Dima -.012.036-.021.097.029.059 O-Man.038.055-.057.029.121-.006.060 Deva -.043.004.035.029-.006.087.040 O-Style.010.038-.032.059.060.040.114
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India Emerging Markets Conference, May 2009 (25) Melvin Tooker 2009 Conclusions Relationships can be defined as: A = expected genes in common G = actual DNA in common T = QTL alleles in common for a trait Full sibs share 50% ± 3.5% of DNA. “Unrelated” animals share more or fewer unknown ancestors than average. Reliability can increase if genomic (G) replace traditional (A) relationships
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India Emerging Markets Conference, May 2009 (26) Melvin Tooker 2009 Where are the Major Genes?
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India Emerging Markets Conference, May 2009 (27) Melvin Tooker 2009 Distribution of Marker Effects (Net Merit)
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India Emerging Markets Conference, May 2009 (28) Melvin Tooker 2009 Distribution of Marker Effects (DPR)
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India Emerging Markets Conference, May 2009 (29) Melvin Tooker 2009 Marker Effects on Website
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India Emerging Markets Conference, May 2009 (30) Melvin Tooker 2009 Marker Effects on Website
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India Emerging Markets Conference, May 2009 (31) Melvin Tooker 2009 Marker Effects on Website
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India Emerging Markets Conference, May 2009 (32) Melvin Tooker 2009 Positive or Negative Traits
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India Emerging Markets Conference, May 2009 (33) Melvin Tooker 2009 From whom did the bad allele come? From whom did the bad allele come? Round Oak Rag Apple Elevation (7HO00058)
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India Emerging Markets Conference, May 2009 (34) Melvin Tooker 2009 Net Merit by Chromosome Freddie (1HO08784) - highest Net Merit bull
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India Emerging Markets Conference, May 2009 (35) Melvin Tooker 2009 Net Merit by Chromosome O Man (7HO06417) – Sire of Freddie
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India Emerging Markets Conference, May 2009 (36) Melvin Tooker 2009 Net Merit by Chromosome Die-Hard (29HO08538) - maternal grandsire
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India Emerging Markets Conference, May 2009 (37) Melvin Tooker 2009 New Chromosomal PTA Query
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India Emerging Markets Conference, May 2009 (38) Melvin Tooker 2009 Chromosomal PTA Query Example
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India Emerging Markets Conference, May 2009 (39) Melvin Tooker 2009 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, Jersey & Brown Swiss breed associations Contributors to Cooperative Dairy DNA Repository (CDDR)
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