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Combination of genotype, pedigree, 

local and foreign information

J. Vandenplas

1,2

, F.G. Colinet

1

, N. Gengler

1,*

University of Liège, Gembloux Agro‐Bio Tech, BelgiumNational Fund for Scientific Research, Brussels, Belgium 64thannual EAAP Meeting, Nantes, France,  August 26th– 30th2013

Introduction 

For genomic prediction

To get reliable GEBV use of multiple sources needed

Traditional traits (i.e., in dairy cattle)

Local genomic evaluations  MACE

Novel traits 

(e.g., milk quality, feed efficiency, methane) Combining different sources of often locally sparse  phenotypic data even more needed 2 64thannual EAAP Meeting, Nantes, France,  August 26th– 30th2013

 Adapting strategies to use multiple sources

Aims

To develop strategies to use simultaneously:

Genotypes,  Pedigree,  Local phenotypes and, Foreign phenotypes

By combining and adapting:

Single‐step genomic evaluations (ssGBLUP) and, Bayesian procedure to integrate external  information* *Vandenplas, J., & Gengler, N. (2012).  J. Dairy Sci. 95: 1513‐1526 

Aims

To develop strategies to use simultaneously:

Genotypes,  Pedigree,  Phenotypes from multiple sources

ssGBAYES

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ssGBLUP 

Single‐step genomic evaluation (ssGBLUP)

Allows direct combination of genomic, pedigree and  phenotypic information

However: current limitation

Only available local phenotypic records can be used 5 64thannual EAAP Meeting, Nantes, France,  August 26th– 30th2013

ssGBLUP 

Single‐step genomic evaluation (ssGBLUP)

Allows direct combination of genomic, pedigree and  phenotypic information

However: current limitation

Only available local phenotypic records can be used 6 64thannual EAAP Meeting, Nantes, France,  August 26th– 30th2013

 In opposition to multi‐step methods 

(e.g., use of local‐EBV and MACE‐EBV in prediction equation step)

ssGBLUP 

Single‐step genomic evaluation (ssGBLUP)

Allows direct combination of genomic, pedigree and  phenotypic information

However: current limitation

Only available local phenotypic records can be used

Reason for this limitation

Local ssGBLUP based on modified system of mixed  model equations (MME) 7 64thannual EAAP Meeting, Nantes, France,  August 26th– 30th2013

Modified MME

ssGBLUP

 : inverse of combined genomic‐ pedigree based (co)variances matrix  : vector of local phenotypes

 : vector of estimated local fixed effects

 : vector of estimated local GEBV

 8 64thannual EAAP Meeting, Nantes, France,  August 26th– 30th2013                            L 1 L 1 * L * L 1 * 1 1 1 1 y R Z' y R X' u β G Z R Z' X R Z' Z R X' X R X' ˆ ˆ 1 0 1 1 * G H G     L y * L βˆ * L

 

*

*1

L 0,G u p  MVN

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As alternative to introduce phenotypes

Also allowing for foreign information

However avoiding double counting

E.g. MACE‐EBV contain our phenotypes

Also avoiding deregression

Potential source of trouble

Be simple and flexible

Allowing to extend to multiple sources

Alternative

9 64thannual EAAP Meeting, Nantes, France,  August 26th– 30th2013

Concept of “Hybrid” ssGBLUP

10 64thannual EAAP Meeting, Nantes, France,  August 26th– 30th2013

       L 1 L 1 * L * L 1 * 1 1 1 1

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 More details later

Assumption: a priori known information on

Source of phenotypic information

Vector of local EBV:       “external”*information Prediction error (co)variances matrix:      

Allows use of simplified models

E.g., Test‐day model  lactation EBV

Bayesian priors

* L L L D

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L

replaced by      and        

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L * “external” = outside of original system of MME 

Using only local information as source

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“Hybrid” ssGBLUP  ssGBAYES

Least square part of LHS of hypothetical  BLUP generating local information RHS of hypothetical BLUP  generating  local information

       L 1 L 1 * L * L 1 * 1 1 1 1

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(4)

Assumption: a priori known information on

Extended to 2 sources of phenotypic information

Vector of local EBV:       1st“external”*information 

Vector of foreign EBV:        2nd“external”*information  Prediction error (co)variances matrices:      ,  Issue: only available for some animals  ,      ,       and      : (partially) unknown

Bayesian priors

13 64thannual EAAP Meeting, Nantes, France,  August 26th– 30th2013 * L L uˆ DL DF L F L D DF F * “external” = outside of original system of MME 

Methods

For both sources: estimation of     

(i=L,F) Available EBV of some animals (so‐called “external”      ) “Internal” animals: prediction of EBV (     ) : genetic (co)variances matrix  14 64thannual EAAP Meeting, Nantes, France,  August 26th– 30th2013 i E i

 

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1

, ˆ ˆ ˆ   IIE EE IE E I i i 1 i i i i u G G u G u MVN p

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i ' i i uE uI uˆ  ˆ ˆ   0 G A G  I i

 Correct propagation of information

Methods

For both sources: estimation of      

(i=L,F) 15 64thannual EAAP Meeting, Nantes, France,  August 26th– 30th2013 i

D

i 1 i G Λ D   

          0 Δ Δ Δ R Δ Λ j j j 1 0 j i  : animals   internal   For traits   ,..., 1  ;    : animals   external   For animals   ,..., 1  ;     t k RE diag n j diag block k

 All matrices      depend only on contributions

due to own records 

i

Λ

Issue

Non‐Independence of information sources

E.g., Local information included in MACE‐EBV 16 64thannual EAAP Meeting, Nantes, France,  August 26th– 30th2013 Lc 1 Lc F 1 F Ff 1 Ff

u

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Vector of foreign  EBV free of local  information Vector of  foreign EBV Vector of local EBV  contributing to  foreign information

 Estimation of external information

free from local information

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Combination of genotype, pedigree, local and 

foreign information (ssGBayes)

Lc 1 Lc F 1 F L 1 L * L Lc F L 1 *

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Methods

17 64thannual EAAP Meeting, Nantes, France,  August 26th– 30th2013 Least square part of  LHS of hypothetical  BLUP of local  information Least square part of  LHS of hypothetical  BLUP of foreign  information free of  local information RHS of hypothetical  BLUP of local  information RHS of hypothetical  BLUP of foreign  information free of  local information

 No double counting of contributions    

Example : 

Walloon genomic evaluation

 ssGBAYES results for milk yield But already used for all INTERBULL traits  1,909 genotyped Holstein bulls and cows  16,234 animals (genotyped and ancestors) 12,046 animals with Walloon EBV (EBVW) 1,981 bulls with MACE EBV (EBVM) 601 bulls with Walloon EBV contributing to MACE (EBVWc)  Reliabilities (REL) for GEBV obtained through inversion of left‐hand side 18 64thannual EAAP Meeting, Nantes, France,  August 26th– 30th2013

Results

 Averaged REL (SD) associated to EBVW, GEBVWand  GEBVW+M‐Wcfor genotyped bulls for milk yield Class of  RELw N EBVW 1 No. of  publishable  bulls GEBVW 2 No. of  publishable bulls GEBVW+M‐Wc3 No. of  publishable  bulls < 0.50 647 0.25  (0.12) 0 0.44  (0.09) 194 0.80 (0.09) 628 0.50 – 0.74 173 0.63  (0.07) 173 0.69  (0.06) 173 0.87 (0.05) 173 ≥ 0.75 390 0.90  (0.07) 390 0.91  (0.06) 390 0.94 (0.04) 390 1REL obtained from Walloon polygenic evaluation

2REL obtained from Walloon genomic evaluation using only EBV W 3REL obtained from Walloon genomic evaluation using EBV

W, EBVMand EBVWc 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 1.00 0.00 0.10 0.200.30 0.40 0.500.60 0.70 0.800.90 1.00 GRELW+M‐Wc REL

Results

 Bulls  Cows

 Bulls not yet included in  national polygenic evaluation  Increase of REL for genotyped animals without MACE 

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Conclusions

Applied to Walloon dairy genomic evaluations

Bayesian approach integrates well MACE results into  ssGBLUP Recovers large amount of phenotypic information More accurate predictions for genotyped animals  and their progeny Correct propagation of all available information 21 64thannual EAAP Meeting, Nantes, France,  August 26th– 30th2013

Combining “s” sources of information

   





s 1, i i 1 i * C s 1, i i 1 *

+

Λ

 

u

=

D

u

G

ˆ

ˆ

General notation

22 64thannual EAAP Meeting, Nantes, France,  August 26th– 30th2013 Least square part of LHS of hypothetical BLUP  for information source i RHS of hypothetical BLUP for information source i

 Potential to improve current    

genomic prediction strategies

Further implications ssGBayes

No deregression

Direct use of EBV from multiple sources

Applicable to multi‐trait models

E.g., external information for correlated and/or 

predictor traits

Open general framework, can be modified to 

accomodate latest genomic models, e.g.:

GWAS models based on ssGBLUP

SNP based single‐step models

23 64thannual EAAP Meeting, Nantes, France,  August 26th– 30th2013 64thannual EAAP Meeting, Nantes, France,  August 26th– 30th2013

Thank you for your attention 

Acknowledgments for financial support

 Service Public of Wallonia SPW – DGO3  through project D31‐1274 DairySNP   National Fund for Scientific Research and  Wallonie Brussels Internationalfor scientific stays

Acknowledgments

 Animal Breeding Association for providing data  CECI for computational resources  Animal and Dairy Science Department,  University of Georgia, Athens, USA  Animal Science Department, University  of Ljubljana, Slovenia

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