Use of DNA information in Genetic Programs .

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Use of DNA information in Genetic Programs.

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Use of DNA information in Genetic Programs. Outline. DNA Information in Genetic Evaluation: DNA Tests Inclusion in Genetic Evaluations Commercial Ranch Genetic Evaluations Sorting Bulls on DNA Genotyping DNA Parent identification. DNA Test Terminology. - PowerPoint PPT Presentation

Transcript of Use of DNA information in Genetic Programs .

Page 1: Use of DNA information in Genetic Programs .

Use of DNA information in Genetic

Programs.

Page 2: Use of DNA information in Genetic Programs .

Outline

1. DNA Information in Genetic Evaluation:

• DNA Tests

• Inclusion in Genetic Evaluations

2. Commercial Ranch Genetic Evaluations

• Sorting Bulls on DNA Genotyping

• DNA Parent identification

Page 3: Use of DNA information in Genetic Programs .

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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• EPD

– Expected Haplotype Effect given sire

genotype

– Polygenic effect

Marker Assisted EPD’s

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Progeny Genotype vs. Sire Genotype

Progeny Genotype

Progeny Phenotype

Progeny Genotype

Progeny Phenotype

Sire Haplotype

Sire Genotype

Dam Haplotype

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-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

blank CG AA CG AG CG GG GG AA GG AG GG GG

Observed Sire Genotype Effects (Constructed from Haplotype Effects)

Four Gametes

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-1.2

-1.0

-0.8

-0.6

-0.4

-0.2

0.0

0.2

0.4

0.6

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-1.0 -0.8 -0.6 -0.4 -0.2 0.0 0.2 0.4 0.6 0.8

EPD (without marker)

Ma

rke

r A

ssis

ted

EP

D

unit slope CG AA CG AG CG GG GG AA GG AG GG GG

WBSF: EPD vs MA-EPD

-0.4

-0.2

0.0

0.2

Page 9: Use of DNA information in Genetic Programs .

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.

Page 12: Use of DNA information in Genetic Programs .

Outline

1. DNA Information in Genetic Evaluation:

• DNA Tests

• Inclusion in Genetic Evaluations

2. Commercial Ranch Genetic Evaluations

• Sorting Bulls on DNA Genotyping

• DNA Parent identification

Page 13: Use of DNA information in Genetic Programs .

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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The probability of uniquely identifying the sire in a group of “N” bulls is:

( Exclusion rate ) N

Sire Identification

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Bulls 0.90 0.95 0.98

2 0.81 0.90 0.96

3 0.73 0.86 0.94

4 0.66 0.81 0.92

5 0.59 0.77 0.90

6 0.53 0.74 0.89

7 0.48 0.70 0.87

8 0.43 0.66 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

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.

Using probabilities then requires a system for genetic evaluation that “models” sire uncertainty.

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Probabilities

Competing sires

Bull 1 = 110/110

Calf = 110/114

Bull 2 = 110/112

If Bull 1: P(110) =1 If Bull 2: P(110) =0.5

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Probabilities

Competing sires

Bull 1 = 220/222

Calf = 220/224

Bull 2 = 224/228

Bull 1: P(220)=0.5 Bull 1: P(224)=0.5

Dam genotype224/224

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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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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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3077 106/6 99 0

3167 A0053 81 0 106/6 11 1

3077 2099J 46 0 106/6 24 0

3074 106/6 87 0 A8035 12 0

3057 8101J 70 0 A0053 19 0

3170 8101J 70 0 A0053 19 0

AID Sire Prob Excl Sire Prob Excl

Example: Bell Ranch Data

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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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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

Experience10 - 15%

chance he still qualifies

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The Phenotypic Representation of a Sire Identification Problem

Animal ScoredGenotype

AnimalGenotype

Will use a four allele locus as an example.

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The Phenotypic Representation of a Sire Identification Problem

Animal ScoredGenotype

AnimalGenotype

P(A1) = 0.5-EP(A2) = 0.5-EP(A3) = EP(A4) = E

E = simple independent error rate

Bull 1:A1/A2

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Population Frequencies

Possible Alleles108 (.4)110 (.3)112 (.2)114 (.1)

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Genotyping Errors

Sire Scored Genotype = 108/110

Assume 4% error

Sire Possible Alleles108 (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

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

108 0.48 0.192 0.144 0.096 0.048

110 0.48 0.192 0.144 0.096 0.048

112 0.02 0.008 0.006 0.004 0.002

114 0.02 0.008 0.006 0.004 0.002

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The Phenotypic Representation of a Sire Identification Problem

Animal ScoredGenotype

AnimalGenotype

P(A1) = 0.5-EP(A2) = EP(A3) = EP(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 0.005 0.005

108 0.005

110 0.005

112 0.005

114 0.985

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Progeny Probabilities

Calf          

    108 110 112 114

    0.985 0.005 0.005 0.005

108 0.005 0.004925 0.000025 0.000025 0.000025

110 0.005 0.004925 0.000025 0.000025 0.000025

112 0.005 0.004925 0.000025 0.000025 0.000025

114 0.985 0.970225 0.004925 0.004925 0.004925

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Bell Ranch

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Progeny Exclusions

  X0135 A1017 X1095

1 6 0 5

2 7 6 0

3 7 1 8

4 5 5 6

5 0 1 3

6 0 5 7

7 6 2 7

8 0 0 1

9 6 6 7

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  X0135 A1017 X1095 X0135 A1017 X1095 9999

1 6 0 5 0 100 0 0

2 7 6 0 0 0 100 0

3 7 1 8 0 0 0 100

4 5 5 6 0 0 0 100

5 0 1 3 100 0 0 0

6 0 5 7 100 0 0 0

7 6 2 7 0 0 0 100

8 0 0 1 67 33 0 0

9 6 6 7 0 0 0 100

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  X0135 A1017 X1095 X0135 A1017 X1095 9999

1 6 0 5 0 100 0 0

2 7 6 0 0 0 100 0

3 7 1 8 0 96 0 4

4 5 5 6 0 1 0 99

5 0 1 3 100 0 0 0

6 0 5 7 100 0 0 0

7 6 2 7 0 74 0 26

8 0 0 1 65 33 2 0

9 6 6 7 0 0 0 100