Marker Assisted Selection Where, When, and How. Lecture 18

Transcription

1 Marker Assisted Selection Where, When, and How 1

2 2 Introduction Quantitative Genetics Selection Based on Phenotype and Relatives Information ε µ β + + = d Z d X Y Chuck = + Y Z Y X A Z Z X Z Z X X X d d d d d d ' ' ' ' ' ' µ β σ σ ε

3 Introduction Molecular Genetics Direct Selection on the Genotype Via Markers or Candidate Genes A Better Mouse Trap Hans 3

4 Introduction Combined (MAS) Selection Based on Phenotype, Relatives Information, and Markers Y = Xβ + Z µ + ε d d MAS 4

5 Marker Assisted How Linked Markers 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) 5

6 How Candidate Genes Direct Selection on Candidate Genes (group) Recombination Not an Issue Selection Index Two Trait Phenotype Candidate Gene Lande and Thompson (1990) 6

7 What Are the Theoretical Optimal Weights In the Short Term? 7

8 Correlated Trait Method Lande and Thompson (1990) Phenotype Yp Polygenes Candidate gene Yc I = b Y + p P b c Y c 8

9 9 Selection Index Solution = 2,, 2 c c p c p Y Y Y Y Y Yp c p b b σ σ σ σ = c c c p c p b b σ σ σ σ

10 Optimal Short Term Weights I = h 2 Y P + ( ) 1 h 2 Y c 10

11 Alternative Independent Trait Method: Gibson (1994) Phenotype Polygenes Yp Candidate gene Yc I + = b Y p' P' b c Y c 11

12 12 Optimal Short Term Weights = 2 2 ' ' 0 0 Y c p Y c p b b σ σ = 2 2 ' ' 0 0 c p c p b b σ σ

13 Optimal Short Term Weights I = h 2 Y P' + Y c I = EBV ( YP ' ) + Y c 13

14 When Will These Advances Cause Animal Breeding To Become A Biotechnology Or Will It Just Be A Passing Fad? Bulfield (1998) 14

15 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? 15

16 Fixation Selection Number Measured Accuracy Mutations Gene Pool Intensity Relatives Selected Drift Inbreeding Number Bred Loss 16

17 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 17

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 18

19 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 19

20 Fixation MAS Selection Number Measured Accuracy Mutations Gene Pool Intensity Relatives Selected Drift Inbreeding Number Bred Loss 20

21 Accuracy of Selection Factors Heritability of the Trait Amount of Information Available From The Individual And Relatives Sex Limited Traits Egg Production 21

22 Accuracy of Selection Cannot Be Measured Directly In Either Sex Disease Resistance Meat Quality Aspects Of Well-being Environment of Selection Environment of Production 22

23 Fixation MAS Selection Number Measured Accuracy Mutations Gene Pool Intensity Relatives Selected Drift Inbreeding Number Bred Loss 23

24 Initial Genetic Variation Start With Elite Populations Highly Selected Favorable Alleles May Have Been Lost in Selection Program Never Had 24

25 Initial Genetic Variation Introgression MAS Select Against Undesirable Background Requires Fewer Generations MAS 25

26 Fixation Selection Number Measured Accuracy MAS Mutations Gene Pool Intensity Relatives Selected Drift Inbreeding Number Bred Loss 26

27 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) 27

28 MAS: Short Term Advantage, Long Term Loss (Gibson, 1994 and others) MAS Phenotypic 28

29 Due to Polygenic Drag (Dekkers (1998, 1999)) Relative Polygenic Response Negative Optimum Short Term Weights 29

30 Fixation Selection Number Measured MAS Accuracy Polygenes Mutations Gene Pool QTL Intensity Relatives Selected Drift Inbreeding Number Bred Loss 30

31 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 31

32 Where: Additional Response (%) From MAS Generation Carcass Sex-limited Phen After Phen Before Broilers % Fat Egg Production Fertility 6 wk wt Meuwissen and Goddard,

33 Non Sex-Limited Traits Body Weight Not Much Help (4%) 33

34 Sex-limited Traits Egg Production Effective (25%) 34

35 Destructive Traits Carcass Quality Disease Resistance Highly Effective (55%) 35

36 Long Term Goals Impacts of Increased Accuracy 36

37 Pure Quantitative Genetics Problem BLUP vs. IOP 37

38 Due to Increased Rate of Inbreeding BLUP IOP 38

39 Fixation BLUP Selection Number Measured Accuracy Relatives Selected Mutations Gene Pool Drift Inbreeding Intensity Number Bred Loss 39

40 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 l I = b i QTL i= 1 i 40

41 Genotypic Selection Increases Rate of Inbreeding Genotypic Phenotypic 41

42 Genotypic Selection Wins Short + Long Term Genotypic Phenotypic 42

43 Fixation Genotypic Selection Number Measured Accuracy Relatives Selected Mutations Gene Pool Drift Inbreeding Intensity Number Bred Loss 43

44 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 44

45 Changing Selection Goals Changes Problem From Multi-trait Single Stage to Multi-trait Multi- Stage (Tandem) Selection Where Traits of Future Stages Are Unknown 45

46 Trait Index 1: First Stage (30 Generations) 46

47 Trait Index 2: Second Stage (Next 30 Generations) 47

48 Trait Index 3: Third Stage (Next 30 Generations) 48

49 Negatively Correlated Traits Genotypic Accuracy Mutations Gene Pool Selection MAS Intensity Relatives Selected Drift Inbreeding Loss 49

50 Uncorrelated Traits Genotypic Accuracy Relatives Selected Mutations Gene Pool Drift Inbreeding Loss 50

51 Optimal Selection Program Any Selection Program That Does Not Also Attempt to Minimize Rate of Inbreeding is Suboptimal Minimize Mating With Relatives 51

52 Alternatives Can the Same Result or Better Be Achieved Without Molecular Information 52

53 Expand Operation Increase Selection Intensity Measure More Animals Keep Number of Breeders the Same 53

54 Response of Phenotypic Selection Relative to MAS With Selection Intensity Phenotypic Better Generation 3 MAS Better Additional Proportion Measured 54

55 Response of Phenotypic Selection Relative to MAS With Selection Intensity Phenotypic Better Generation 8 Additional Proportion Measured 55

56 Conclusion Choice is Economics And Risk/Benefit 56

57 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. 57

58 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 58