2007 Melvin Tooker Animal Improvement Programs Laboratory USDA Agricultural Research Service, Beltsville, MD, USA

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Presentation transcript:

2007 Melvin Tooker Animal Improvement Programs Laboratory USDA Agricultural Research Service, Beltsville, MD, USA An Introduction to Genomics

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

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

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

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

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)

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

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.

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

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

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

India Emerging Markets Conference, May 2009 (12) Melvin Tooker 2009 Genomic Pedigree

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

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

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

India Emerging Markets Conference, May 2009 (16) Melvin Tooker 2009 Translate Haplotype to Genotype agatctagatcg ctgtagcgatcg

India Emerging Markets Conference, May 2009 (17) Melvin Tooker 2009 Genotype Pedigree Count number of second allele = homozygous for first allele (alphabetically) 1 = heterozygous 2 = homozygous for second allele (alphabetically)

India Emerging Markets Conference, May 2009 (18) Melvin Tooker 2009 Genotype Data for Elevation Chromosome

India Emerging Markets Conference, May 2009 (19) Melvin Tooker 2009 Genotype Data from Inbred Bull Chromosome 24 of Megastar

India Emerging Markets Conference, May 2009 (20) Melvin Tooker 2009 Genotype Parents and Grandparents Manfred O-Man Jezebel O-Style Teamster Deva Dima

India Emerging Markets Conference, May 2009 (21) Melvin Tooker 2009 Expected Relationship Matrix 1 1HO9167 O-Style PGSPGDMGSMGDSireDamBull Manfred Jezebel Teamster Dima O-Man Deva O-Style Calculated assuming that all grandparents are unrelated

India Emerging Markets Conference, May 2009 (22) Melvin Tooker 2009 Pedigree Relationship Matrix 1HO9167 O-Style PGSPGDMGSMGDSireDamBull Manfred Jezebel Teamster Dima O-Man Deva O-Style

India Emerging Markets Conference, May 2009 (23) Melvin Tooker 2009 Genomic Relationship Matrix 1HO9167 O-Style PGSPGDMGSMGDSireDamBull Manfred Jezebel Teamster Dima O-Man Deva O-Style

India Emerging Markets Conference, May 2009 (24) Melvin Tooker 2009 Difference (Genomic – Pedigree) 1HO9167 O-Style PGSPGDMGSMGDSireDamBull Manfred Jezebel Teamster Dima O-Man Deva O-Style

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

India Emerging Markets Conference, May 2009 (26) Melvin Tooker 2009 Where are the Major Genes?

India Emerging Markets Conference, May 2009 (27) Melvin Tooker 2009 Distribution of Marker Effects (Net Merit)

India Emerging Markets Conference, May 2009 (28) Melvin Tooker 2009 Distribution of Marker Effects (DPR)

India Emerging Markets Conference, May 2009 (29) Melvin Tooker 2009 Marker Effects on Website

India Emerging Markets Conference, May 2009 (30) Melvin Tooker 2009 Marker Effects on Website

India Emerging Markets Conference, May 2009 (31) Melvin Tooker 2009 Marker Effects on Website

India Emerging Markets Conference, May 2009 (32) Melvin Tooker 2009 Positive or Negative Traits

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)

India Emerging Markets Conference, May 2009 (34) Melvin Tooker 2009 Net Merit by Chromosome Freddie (1HO08784) - highest Net Merit bull

India Emerging Markets Conference, May 2009 (35) Melvin Tooker 2009 Net Merit by Chromosome O Man (7HO06417) – Sire of Freddie

India Emerging Markets Conference, May 2009 (36) Melvin Tooker 2009 Net Merit by Chromosome Die-Hard (29HO08538) - maternal grandsire

India Emerging Markets Conference, May 2009 (37) Melvin Tooker 2009 New Chromosomal PTA Query

India Emerging Markets Conference, May 2009 (38) Melvin Tooker 2009 Chromosomal PTA Query Example

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 – , Agriculture Research Service Holstein, Jersey & Brown Swiss breed associations Contributors to Cooperative Dairy DNA Repository (CDDR)