A new Marker-Assisted BLUP genomic evaluation for French dairy breeds

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A new Marker-Assisted BLUP genomic evaluation for French dairy breeds Pascal Croiseau, Aurélia Baur, David Jonas, Chris Hoze, Julie Promp, Didier Boichard, Sébastien Fritz, Vincent Ducrocq *

Genomic evaluation in France : 2009-2014 Holstein, Normande, Montbéliarde then Brown Swiss A Marker-Assisted BLUP model with pre-detected QTL (via an LDLA approach) traced using haplotypes of 3 to 5 SNP 300 to 700 QTL per trait a residual polygenic effect (explaining 30-50% of total genetic variance) using pedigree information imputation LD 50k, with DagPhase (Druet & George, 2010) phases needed, created using DagPhase Reference populations consisting of bulls only

Previous model: limits Imputation could be improved: DagPhase seemed less efficient than initially Our research projects showed that 500 QTL did not give maximal accuracy Large residual polygenic variance penalized sons / daughters of bulls with no progeny test information Time consuming computations (old software)

Imputation Software comparison FImpute (Sargolzaei et al, 2011) is as accurate as Beagle in populations with a dense pedigree information Accuracy increased from 98.0 % to 99.2% Fimpute is at least 3 times faster Can impute the whole population in one run => Switch to Fimpute (with commercial licence)

A new genomic model QTL size Large Moderate Small Tiny Genomic evaluation traced with markers haplotype effects Consider their sum only: ĥ j DGV = + j 1,... K u ˆ mˆ ~ N 0, pedigree relationship matrix j' j' ~ N 0, genomic relationship hˆ j matrix

g i j 1 In practice n n n i g i ui ( ij 1 ( hij 12) hg + iji2) ui ( hij 1 hij 2) j 1 j 1 j 1 Trait dependent Trait independent n + k g u h h ( h ) ij1 hij2 ( SNP j 1 ij1 SNP Genomic relationships via EuroG10K chip: System size = constant New software to cope with very large increase in number of genotyped animals strategy: read genotypes and store in memory preconditioned conjugate gradient with iteration on data in memory ij2 )

QTL modelisation First step: QTL (SNP) detection with GWAS Bayes Cp, K (=1000 3000 6000) largest SNP selected To modelize each QTL, we use: SNP QTL information Haplotype including the SNP and flanking markers Haplotype including the SNP and the «best» combination of SNP in a window of 10 SNP (David Jonas et al., this congress) The optimal combination is the one with the highest number of alleles and the most homogeneous distribution of these alleles in the population.

Reference populations Reference population Learning Validation Normande 1945 385 Montbéliarde 2115 535 Brown Swiss 5557 458 Holstein 27309 3391 Comparison criteria : correlation (GEBV t-4, DYD t ), regression slope

Corr (GEBV, DYD) 0.70 Validation results: all breeds 0.65 0.60 0.55 GBLUP BAYESCpi 0.50 0.45 0.40 1K 3K 6K 1K 3K 6K 1K 3K 6K 1K 3K 6K 33 41 27 34 Normande Montbéliarde Brown Swiss Holstein

Validation results: all breeds 0.70 0.65 0.60 0.55 0.50 GBLUP BAYESCp SNP_A Haplo_flk_A 0.45 0.40 1K 3K 6K 1K 3K 6K 1K 3K 6K 1K 3K 6K 33 41 27 34 Normande Montbéliarde Brown Swiss Holstein

Validation results: all breeds 0.70 0.65 0.60 0.55 0.50 0.45 GBLUP BAYESCp SNP_A Haplo_flk_A Haplo_sel_A Haplo_sel_G 0.40 1K 3K 6K 1K 3K 6K 1K 3K 6K 1K 3K 6K 33 41 27 34 Normande Montbéliarde Brown Swiss Holstein

Validation results: all breeds 0.70 0.65 0.60 0.55 0.50 0.45 GBLUP BAYESCp SNP_A Haplo_flk_A Haplo_sel_A Haplo_sel_G 0.40 1K 3K 6K 1K 3K 6K 1K 3K 6K 1K 3K 6K 33 41 27 34 Normande Montbéliarde Brown Swiss Holstein

Correlation Validation results: all breeds 0.70 0.65 1K 3K - 6K 0.60 0.55 0.50 0.45 SNP_A Haplo_flk_A Haplo_sel_A Haplo_sel_G 0.40 1K 3K 1K 3K 1K 3K 1K 3K 33 41 27 34 Normande Montbéliarde Brown Swiss Holstein

Validation results: all breeds 0.70 0.65 1K 3K - 6K 0.60 0.55 0.50 0.45 SNP_A Haplo_flk_A Haplo_sel_A Haplo_sel_G 0.40 3K 6K 3K 6K 3K 6K 3K 6K 33 41 27 34 Normande Montbéliarde Brown Swiss Holstein

Validation results: all breeds 0.70 0.65 0.60 0.55 0.50 0.45 GBLUP BAYESCp SNP_A Haplo_flk_A Haplo_sel_A Haplo_sel_G 0.40 1K 3K 6K 1K 3K 6K 1K 3K 6K 1K 3K 6K 33 41 27 34 Normande Montbéliarde Brown Swiss Holstein

New evaluation: overall impact Correlations PA/GEBV at year t-4 and DYD at year t PA / GS 2010 / GS 2015 Production Type Functional traits Increase in reliability: Normande: +0.11 Montbéliarde : +0.10 Holstein : +0.08 Brown Swiss : +0.11

A new genomic evaluation in Spring 2015 Substantial gain in reliability New software much faster easy to extend to include causal mutations Use of genomic relationship matrix leads to system size = constant much less sensitive to missing pedigree information, to absence of phenotypes of sires, to absence of foreign information Post-processing to force regression slope for candidates to be ~1 also being developed for other French minor breeds

A new Marker-Assisted BLUP genomic evaluation for French dairy breeds Pascal Croiseau, Aurélia Baur, David Jonas, Chris Hoze, Julie Promp, Didier Boichard, Sébastien Fritz, Vincent Ducrocq *