1Lecture 18

Marker Assisted SelectionWhere, When, and How

Lecture 18

2Lecture 18

IntroductionQuantitative Genetics

– Selection Based on Phenotype and Relatives Information

εµβ ++= ddZXYChuck

=

+ − YZYX

AZZXZ

ZXXX

dd

ddd

d

''''

2

21'' µ

β

σσ ε

3Lecture 18

Introduction• Molecular Genetics

– Direct Selection on the Genotype Via Markers or Candidate Genes

Hans

A Better Mouse Trap

4Lecture 18

Introduction

• Combined (MAS)– Selection Based on

Phenotype, Relatives Information, and Markers

εµβ ++= ddZXY MAS

5Lecture 18

HowLinked Markers

• Marker Assisted– Recombination an Issue– Must use IBD methods

• Single Marker-– Fernando and Grossman (1989)

• Multiple Marker– Goddard (1992), – Meuwissen and Goddard (1996)

• Multi-Marker, Multi-Stage– Xie and Xu (1998)

6Lecture 18

HowCandidate Genes

• Direct Selection on Candidate Genes (group)– Recombination Not an Issue– Selection Index

• Two Trait– Phenotype– Candidate Gene

• Lande and Thompson (1990)

7Lecture 18

What Are the Theoretical Optimal Weights In the Short Term?

8Lecture 18

Phenotype

Polygenes Candidate gene

Correlated Trait MethodLande and Thompson (1990)

Yp

Yc

ccPp YbYbI +=

9Lecture 18

Selection Index Solution

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2

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,2

ccp

cp

YYY

YYYp

c

p

bb

σσσσ

=

22

22

cc

cp

c

p

bb

σσσσ

10Lecture 18

Optimal Short Term Weights

( ) cP YhYhI 22 1−+=

11Lecture 18

Phenotype

Polygenes Candidate gene

AlternativeIndependent Trait Method: Gibson (1994)

Yp’ Yc

ccPp YbYbI += ''

12Lecture 18

Optimal Short Term Weights

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00

cY

pY

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p

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σσ

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13Lecture 18

Optimal Short Term Weights

cP

cP

YYEBVIYYhI

+=+=

)( '

'2

14Lecture 18

When Will These Advances Cause

Animal Breeding To Become A Biotechnology Or Will It Just Be

A Passing Fad?Bulfield (1998)

15Lecture 18

Quest of Commercial Breeders

• Maximize Long And Short Term Response For All Traits Of Economic Importance – Selection Intensity– Accuracy Of Selection– Initial Genetic Variation– Effective Population Size

• How Does Molecular Genetic Impact Each of These?

16Lecture 18

Fixation

Loss

IntensityGene Pool

Selection

DriftInbreeding

Accuracy

RelativesSelected

Number Measured

Number Bred

Mutations

17Lecture 18

Selection Intensity• Function of Number of

Animals Tested– Costs and Space Limit

Numbers• Egg Production In The Dam

Line Of Broilers– Multi-stage Selection

• First Stage– Chicks– MAS Selection

• Second Stage– Hens– Phenotypic Selection

18Lecture 18

Lost Selection Intensity• Males In Poultry

Layer Programs– Usually Only One Or

Two Roosters Are Kept From Each Full Sib Family And Those Are Chosen At Random

19Lecture 18

BLUP Cannot Help– Selection Using

Ancestors Information Cannot Distinguish EBV’s Between Full Sibs

– Must Progeny Test: Too Costly

– MAS To The Rescue– Tremendous Increase

in Selection Intensity Within Family

20Lecture 18

Fixation

Loss

IntensityGene Pool

Selection

DriftInbreeding

Accuracy

RelativesSelected

Number Measured

Number Bred

Mutations

MAS

21Lecture 18

Accuracy of Selection• Factors

– Heritability of the Trait – Amount of Information

Available From The Individual And Relatives

• Sex Limited Traits– Egg Production

22Lecture 18

Accuracy of Selection• Cannot Be Measured

Directly In Either Sex – Disease Resistance– Meat Quality– Aspects Of Well-being

Environment of Selection

Environment of Production

23Lecture 18

Fixation

Loss

IntensityGene Pool

Selection

DriftInbreeding

Accuracy

RelativesSelected

Number Measured

Number Bred

Mutations

MAS

24Lecture 18

Initial Genetic Variation• Start With Elite

Populations– Highly Selected

• Favorable Alleles – May Have Been Lost

in Selection Program– Never Had

25Lecture 18

Initial Genetic Variation• Introgression

– MAS• Select Against

Undesirable Background

• Requires Fewer Generations

MAS

26Lecture 18

Fixation

Loss

IntensityGene Pool

Selection

DriftInbreeding

Accuracy

RelativesSelected

Number Measured

Number Bred

Mutations

MAS

27Lecture 18

Complex Issues

• Require Simulations• See Dekkers and Hospital (2002) for Review• Impact of Selecting for Single QTL

– Gibson (1994)– Ruane Colleau (1995, 1996)– Dekkers (1998, 1999)– Meuwissen and Goddard (1996)

28Lecture 18MAS Phenotypic

MAS: Short Term Advantage, Long Term Loss (Gibson, 1994 and others)

29Lecture 18

Due to Polygenic Drag (Dekkers (1998, 1999))

OptimumShort TermWeights

Relative Polygenic ResponseNegative

30Lecture 18

Fixation

Loss

IntensityGene Pool

Selection

DriftInbreeding

Accuracy

RelativesSelected

Number Measured

Number Bred

Mutations

QTLPolygenes

MAS

31Lecture 18

Optimize The Short Term

• Meuwissen and Goddard (1996)– There Will Be a Series of New QTL

Found Sequentially, Concentrate on the Short Term

– Tandem Selection on QTL’s + Phenotype

32Lecture 18

Generation

Where: Additional Response (%) From MAS

Meuwissen and Goddard, 1996

0

20

40

60

80

100

1 2 3 5

Phen BeforePhen After

Sex-limitedCarcass

2459152530

3838 37 31 21

64 62 5539

6 wk wtFertility

Broilers

Egg Production% Fat

33Lecture 18

Non Sex-Limited TraitsBody Weight

Not Much Help (4%)

34Lecture 18

Sex-limited TraitsEgg ProductionEffective (25%)

35Lecture 18

Destructive TraitsCarcass Quality

Disease ResistanceHighly Effective (55%)

36Lecture 18

Long Term Goals

Impacts of Increased Accuracy

37Lecture 18

Pure Quantitative Genetics Problem BLUP vs. IOP

38Lecture 18

Due to Increased Rate of Inbreeding

BLUP

IOP

39Lecture 18

Fixation

Loss

IntensityGene Pool

Selection

DriftInbreeding

Accuracy

RelativesSelected

Number Measured

Number Bred

Mutations

BLUP

40Lecture 18

What Is the Impact of Genotypic Selection on Rate of Inbreeding, Loss of Genetic Variance, Long Term Response?

• Assume all Alleles at All Loci Are Known• Cannot Fix All Alleles in One Generation• Select on Index of All QTL’s at All Loci

i

l

iiQTLbI ∑

=

=1

41Lecture 18

Genotypic Selection Increases Rate of Inbreeding

Genotypic

Phenotypic

42Lecture 18

Phenotypic

Genotypic

Genotypic Selection Wins Short + Long Term

43Lecture 18

Fixation

Loss

IntensityGene Pool

Selection

DriftInbreeding

Accuracy

RelativesSelected

Number Measured

Number Bred

Mutations

Genotypic

44Lecture 18

Selection Goals Change

“In Real Life Selection Objectives - Especially In An Industry Like

Ours - Change. So Do The Best You Can In The Short Run”

Max Rothschild

45Lecture 18

Changing Selection Goals

Changes Problem From Multi-trait Single Stage to Multi-trait Multi-

Stage (Tandem) Selection Where Traits of Future Stages Are

Unknown

46Lecture 18

Trait Index 1: First Stage (30 Generations)

47Lecture 18

Trait Index 2: Second Stage (Next 30 Generations)

48Lecture 18

Trait Index 3: Third Stage (Next 30 Generations)

49Lecture 18Loss

Intensity

Gene Pool

DriftInbreeding

Accuracy

RelativesSelected

Mutations

Genotypic

Negatively Correlated Traits

Selection

MAS

50Lecture 18Loss

Gene Pool

DriftInbreeding

Accuracy

RelativesSelected

Mutations

Genotypic

Uncorrelated Traits

51Lecture 18

Optimal Selection Program

• Any Selection Program That Does Not Also Attempt to Minimize Rate of Inbreeding is Suboptimal

• Minimize Mating With Relatives

52Lecture 18

AlternativesCan the Same Result or Better Be

Achieved Without Molecular Information

53Lecture 18

Expand Operation

Increase Selection IntensityMeasure More Animals

Keep Number of Breeders the Same

54Lecture 18

Generation 3

Response of Phenotypic Selection Relative to MAS With Selection Intensity

MAS Better

Phenotypic Better

Additional Proportion Measured

55Lecture 18

Generation 8

Response of Phenotypic Selection Relative to MAS With Selection Intensity

Phenotypic Better

Additional Proportion Measured

56Lecture 18

Conclusion

Choice is EconomicsAnd

Risk/Benefit

57Lecture 18

Lab Problem 1• Each Group Chose A Different Commodity

Group from below.– Fish, Shellfish, Dairy, Beef, Swine, Sheep (wool),

Sheep (meat), Horse, Broiler, Layer, Swine– What are the critical traits for each commodity group?– Subdivide Traits into categories where you feel MAS

will be Highly, Moderate, or Minor effective in improving the trait. Give Reason for putting into each category.

58Lecture 18

Lab Problem 2

• From the paper by Dekkers and Hospital– List the top 3 most important conclusions,

opinions, or findings– Discuss why you listed those in the top 3