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Use of DNA information in Genetic Programs.
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Outline DNA Information in Genetic Evaluation: DNA Tests
Inclusion in Genetic Evaluations Commercial Ranch Genetic Evaluations Sorting Bulls on DNA Genotyping DNA Parent identification
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Discovery, Validation, Assessment and Application
DNA Test Terminology Discovery, Validation, Assessment and Application Discovery: Process of identifying QTL Validation: Process of replicating results in independent data through blind testing Assessment: Process of evaluating the effect of the QTL in a broader context (other traits and environments) Application: Process of using the DNA information in genetic decisions
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DNA Tests for Carcass Merit Traits
Thyroglobulin Calpain (MARC Discovery) Calpistatin Leptin Three QTL from NCBA Carcass Merit Project (genes unknown) DGAT1
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Marker Assisted EPD’s EPD
Expected Haplotype Effect given sire genotype Polygenic effect
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Progeny Genotype vs. Sire Genotype
Progeny Phenotype Sire Haplotype Sire Genotype Dam Haplotype The mixed model analysis is most appropriate as it accounts for differences among sires, e.g., a bull might have a very good/bad Breeding Value for marbling score but have the reverse GeneSTAR marbling genotype Progeny Genotype Progeny Phenotype
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Four Gametes
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WBSF: EPD vs MA-EPD
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Commercial Ranch Project and the need for using DNA in sire assignments.
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Bull Sorting
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Create genetically diverse groups.
Objective: is to maximize the probability of uniquely identifying one sire to a calf.
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Outline DNA Information in Genetic Evaluation: DNA Tests
Inclusion in Genetic Evaluations Commercial Ranch Genetic Evaluations Sorting Bulls on DNA Genotyping DNA Parent identification
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Verification Verification: Verifying that the putative parent is the real parent. In the seedstock industry, pedigree integrity is the primary reason for DNA testing for parent verification AI sires, ET cows and calves, random checks.
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Identification Identification: Identifying a parent from a group of potential parents (e.g., multiple-sire breeding pastures).
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Practical Application
We are currently developing a program for genetic evaluation for the commercial sector. A problem is that the large commercial ranches use multiple-sire pastures so DNA testing for identification becomes necessary.
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Perfect World Begin by assuming that genotypes are scored without error. Process of excluding bulls. A mismatch between the genotype of the putative sire and the calf in question. Sire = 110/110 Calf = 112/114
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Panel Exclusion Rate Measure of the effectiveness of a DNA panel to exclude an animal as a parent. Probability of excluding as the parent any animal drawn at random from the population.
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Sire Identification The probability of uniquely identifying the sire in a group of “N” bulls is: ( Exclusion rate ) N
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Two or more qualify 18% of the time
Bulls 0.90 0.95 0.98 2 0.81 0.96 3 0.73 0.86 0.94 4 0.66 0.92 5 0.59 0.77 6 0.53 0.74 0.89 7 0.48 0.70 0.87 8 0.43 0.85 9 0.39 0.63 0.83 10 0.35 0.60 0.82 Two or more qualify 18% of the time
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Multiple Qualifying Sires
Could run more markers (a second panel). If this was a seedstock problem probably would. In the commercial program however this is not cost effective, so we compute the probability that each qualifying sire is the true sire.
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Commercial Genetic Evaluation
Using probabilities then requires a system for genetic evaluation that “models” sire uncertainty. Under a sire uncertainty model do not need to uniquely identify the sire. We will use the probability associated with each bull of being the sire.
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Probabilities Competing sires Bull 1 = 110/110 Bull 2 = 110/112
Calf = 110/114 If Bull 1: P(110) =1 If Bull 2: P(110) =0.5
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Probabilities Competing sires Bull 1 = 220/222 Bull 2 = 224/228
Dam genotype 224/224 Calf = 220/224 Bull 1: P(220)=0.5 Bull 1: P(224)=0.5
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0.5 of his calves will have the calf genotype in question.
Two Qualifying Bulls Bull 1: P(locus one) = 1.0 P(locus two) = 0.5 0.5 of his calves will have the calf genotype in question. Locus 1: 110/114 Locus 2: 220/224
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0.25 of his calves will have the calf genotype in question.
Two Qualifying Bulls Bull 2: P(locus one) = 0.5 P(locus two) = 0.5 0.25 of his calves will have the calf genotype in question. Locus 1: 110/114 Locus 2: 220/224
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Two Qualifying Bulls Bull 1 = 0.50 Bull 2 = 0.25
Bull 1 is twice as likely as bull 2 to be the sire so the probability of each bull is then: Bull 1 = 2/3 Bull 2 = 1/3
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Example: Bell Ranch Data
3077 106/6 99 3167 A0053 81 11 1 2099J 46 24 3074 87 A8035 12 3057 8101J 70 19 3170 AID Sire Prob Excl Sire Prob Excl
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Scoring genotypes is NOT a process without error.
Real World Scoring genotypes is NOT a process without error. A mismatch between the genotype of the sire and calf in question does not exclude the bull. Sire = 110/110 Calf = 112/114
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Types of Scoring Errors
Independent of genotype (2-base pair repeats): Base pair mis-reads (usually two bases off) More likely in large DNA repeat segments Dependent of genotype (2-base pair repeats): Heterozygotes for alleles differing by two bases are read as a homozygote for the smaller allele: genotype 110/112 => scored as 110/110
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chance he still qualifies
Real World A mismatch between the genotype of the sire and calf in question does not exclude the bull. Sire = 110/110 Calf = 112/114 Experience % chance he still qualifies
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The Phenotypic Representation of a Sire Identification Problem
Animal Genotype Animal Scored Genotype Will use a four allele locus as an example.
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The Phenotypic Representation of a Sire Identification Problem
Animal Genotype Animal Scored Genotype P(A1) = 0.5-E P(A2) = 0.5-E P(A3) = E P(A4) = E E = simple independent error rate Bull 1: A1/A2
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Population Frequencies
Possible Alleles 108 (.4) 110 (.3) 112 (.2) 114 (.1)
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Sire Scored Genotype = 108/110
Genotyping Errors Sire Scored Genotype = 108/110 Assume 4% error Sire Possible Alleles 108 (0.48) 110 (0.48) 112 (0.02) 114 (0.02)
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Progeny Probabilities
Dam 108 110 112 114 Sire 0.4 0.3 0.2 0.1 0.48 0.02
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Progeny Probabilities
Dam 108 110 112 114 Sire 0.4 0.3 0.2 0.1 0.48 0.192 0.144 0.096 0.048 0.02 0.008 0.006 0.004 0.002
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The Phenotypic Representation of a Sire Identification Problem
Animal Genotype Animal Scored Genotype P(A1) = 0.5-E P(A2) = E P(A3) = E P(A4) = 0.5-E E = simple independent error rate Calf: A1/A4
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Progeny Probabilities
Calf 108 110 112 114 0.985 0.005
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Progeny Probabilities
Calf 108 110 112 114 0.985 0.005
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Bell Ranch
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Progeny Exclusions X0135 A1017 X1095 1 6 5 2 7 3 8 4 9
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X0135 A1017 X1095 9999 1 6 5 100 2 7 3 8 4 67 33 9
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X0135 A1017 X1095 9999 1 6 5 100 2 7 3 8 96 4 99 74 26 65 33 9
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