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www.qualitasag.ch | 1
10 ans de sélection génomiqueen Suisse
Plateforme des clubs de race
Vache Mère Suisse
15 décembre 2017
juerg.moll@qualitasag.ch
www.qualitasag.ch | 2
Un concept central dans l‘élevage...
Phénotype Génotype Environement
• Performances• Exterieur• Fitness• Comportement
• Génome • Détention• Affouragement
Concept
www.qualitasag.ch | 3
Amélioration de la prédisposition génétique des animaux pourdes critères déterminés en ce qui concerne la performance et la santé
Connaissance du génome des animaux d‘élevage le plus:• Tôt• Précis• Bon marché
?
?
But de l‘élevage
www.qualitasag.ch | 4
La manière „classique“:
• Performances (Données abattage, sevrage, etc.)
• Conduite du herdbook
• Estimation des valeurs d‘élevage basée là-dessus
La “nouvelle“ manière:
• Performances (Données abattage, sevrage, etc.)
• Conduite du herdbook
• Estimation des valeurs d‘élevage basée là-dessus
• Informations du génome
= sélection génomique
Prédisposition génétiqueComment se procurer les connaissances sur le génome?
www.qualitasag.ch | 5
• Directement c‘est difficile– Critères quantitatifs (beaucoup de gènes influencent un critère)– Peu de connaissance sur la location et l‘effet
• Sélection génomique travaille avec des marqueurs nommésSNP
• SNP: Single Nucleotide Polymorphism– Changement ponctuel dans le génome (1 bp de long)– Présents en grande quantité– Uniquement 2 variantes
• Les marqueurs nous montre l‘effet du gène puisqu‘ils se trouvent à proximité des gènes– Déséqulibre de liaison (Linkage Disequilibrium)
Découvrir les gènes – COMMENT?
www.qualitasag.ch | 6
SNP1
CAGTATCGTAATAATAATAATAAGTCCTGGGCCTAAACCTGCAAGGTTTCGATATTGGCCCCCGG GTCATAGCATTATTATTATTATTCAGGACCCGGATTTGGACGTTCCAAAGCTATAACCGGGGGCC
CAGTATCGTAATAATAATAATAAGTCCTGGGCCTAAACCTGCAAGGTTTCGATATTGGCCCCCGG GTCATAGCATTATTATTATTATTCAGGACCCGGATTTGGACGTTCCAAAGCTATAACCGGGGGCC
CAGTATCGTAATAATAATAATAAGTCCTGGGCCTAAACCTGCAAGGTTTCGATATTGGCCCCCGG GTCATAGCATTATTATTATTATTCAGGACCCGGATTTGGACGTTCCAAAGCTATAACCGGGGGCC
CAGTATCGTAATAATAATAATAAGTCCTGGGCCTAAACCTGCAAGGTTTCGATATTGGCCCCCGG GTCATAGCATTATTATTATTATTCAGGACCCGGATTTGGACGTTCCAAAGCTATAACCGGGGGCC
CAGTATCGTAATAATAATAATAAGTCCTGGGCCTAAACCTGCAAGGTTTCGATATTGGCCCCCGG GTCATAGCATTATTATTATTATTCAGGACCCGGATTTGGACGTTCCAAAGCTATAACCGGGGGCC
CAGTATCGTAATAATAATAATAAGTCCTGGGCCTAAACCTGCAAGGTTTCGATATTGGCCCCCGG GTCATAGCATTATTATTATTATTCAGGACCCGGATTTGGACGTTCCAAAGCTATAACCGGGGGCC
CAGTATCGTAATAATAATAATAAGTCCTGGGCCTAAACCTGCAAGGTTTCGATATTGGCCCCCGG GTCATAGCATTATTATTATTATTCAGGACCCGGATTTGGACGTTCCAAAGCTATAACCGGGGGCC
CAGTATCGTAATAATAATAATAAGTCCTGGGCCTAAACCTGCAAGGTTTCGATATTGGCCCCCGG GTCATAGCATTATTATTATTATTCAGGACCCGGATTTGGACGTTCCAAAGCTATAACCGGGGGCC
AAABBB AAAB BBBB AA ABBB
SNP2
SNP3
SNP4
SNP5
SNP6
SNP7
SNP8
SNP10
SNP9
.........
Estimation des effets?
www.qualitasag.ch | 7
1) Comparaison entre les valeurs d‘élevage avec les génotypes
– L‘estimation des effets se fait à l‘aide d‘une base de données SNP ainsi que les valeurs d‘élevageconventionnelles des taureaux* testés sur la descendance
– Population de référence (Population de calibrage, échantillon)
2) Estimation des valeurs d‘élevage génomiquespour d‘autres animaux à l‘aide de la formule 1)
* Parfois les vaches peuvent faire partir de la population de référence;ces animaux doivent être choisis aléatoirement
Estimation des effets - Principe
www.qualitasag.ch | 8
kg L
ait
BBABAA
Exemple à l‘aide d‘un SNP:
Effet SNP
L‘effet d‘unallèle-B supplémentaireapporte +10kg
Estimation des effets
www.qualitasag.ch | 9
Le calcul de la valeur d‘élevage est très simple, car on doitadditionner tous les effets des SNP
SNP1
CAGTATCGTAATAATAATAATAAGTCCTGGGCCTAAACCTGCAAGGTTTCGATATTGGCCCCCGG GTCATAGCATTATTATTATTATTCAGGACCCGGATTTGGACGTTCCAAAGCTATAACCGGGGGCC
CAGTATCGTAATAATAATAATAAGTCCTGGGCCTAAACCTGCAAGGTTTCGATATTGGCCCCCGG GTCATAGCATTATTATTATTATTCAGGACCCGGATTTGGACGTTCCAAAGCTATAACCGGGGGCC
CAGTATCGTAATAATAATAATAAGTCCTGGGCCTAAACCTGCAAGGTTTCGATATTGGCCCCCGG GTCATAGCATTATTATTATTATTCAGGACCCGGATTTGGACGTTCCAAAGCTATAACCGGGGGCC
CAGTATCGTAATAATAATAATAAGTCCTGGGCCTAAACCTGCAAGGTTTCGATATTGGCCCCCGG GTCATAGCATTATTATTATTATTCAGGACCCGGATTTGGACGTTCCAAAGCTATAACCGGGGGCC
CAGTATCGTAATAATAATAATAAGTCCTGGGCCTAAACCTGCAAGGTTTCGATATTGGCCCCCGG GTCATAGCATTATTATTATTATTCAGGACCCGGATTTGGACGTTCCAAAGCTATAACCGGGGGCC
CAGTATCGTAATAATAATAATAAGTCCTGGGCCTAAACCTGCAAGGTTTCGATATTGGCCCCCGG GTCATAGCATTATTATTATTATTCAGGACCCGGATTTGGACGTTCCAAAGCTATAACCGGGGGCC
CAGTATCGTAATAATAATAATAAGTCCTGGGCCTAAACCTGCAAGGTTTCGATATTGGCCCCCGG GTCATAGCATTATTATTATTATTCAGGACCCGGATTTGGACGTTCCAAAGCTATAACCGGGGGCC
CAGTATCGTAATAATAATAATAAGTCCTGGGCCTAAACCTGCAAGGTTTCGATATTGGCCCCCGG GTCATAGCATTATTATTATTATTCAGGACCCGGATTTGGACGTTCCAAAGCTATAACCGGGGGCC
Veau 1
AAABBB AAAB BBBB AA ABBB
SNP2
SNP3
SNP4
SNP5
SNP6
SNP7
SNP8
SNP10
SNP9
+1.3 -0.1 +0.5 +0 -0.4 +3.8 +38.3 +4.1 -5.7 +2.7
VE = 2*(+1.3)+1*(-0.1)+1*(+0.5)+0*(0)+0*(-0.4)+ 2*(+3.8)+2*(+38.3)+0*(+4.1)+2*(-5.7)+1*(+2.7)
VE = 81.2 = Valeur d‘élevage directe (DGZW)
Calcul de la VE génomique
www.qualitasag.ch | 10
20152010200520001995
Population de référence (taureaux testés sur la descendance)Candidats de
sélection
Estimation des effets
Somme des effetsSNP (DGZW)
Estimation des effets
www.qualitasag.ch | 11
2005
Population de référence
Estimation des effets
Somme des effetsSNP (DGZW)
Taureaux de validation
Validation:
Corrélation entre DGZW et VE
conventionnelle
2015201020001995
Sécurité VE génomique : Validation
www.qualitasag.ch | 12
Critère BV RH/HO
Production (Ekg) 49 % 56 %
Cellules 43 % 44 %
DL 43 %
(25 - 56) 43 % (21 - 61)
Fertilité 38 % 35 %
Durée d‘utilisation 27 % 42 %
Sécurité (B%) DGZW
www.qualitasag.ch | 13
Valeur d‘élevage (VE): „conventionnelle“ estime, sans les informations des marqueurs
Valeur d‘élevage directe genomique (DGZW) estimeuniquement l‘effet des marqueurs
Valeur d‘élevage génomique optimisée (GOZW) estimesur la base de données traditionnelles ainsi que les infomations des marqueurs (Combinaison de VE et DGZW).
Définition
VE-Type conventionnelle
Déclaration GOZW Grouped‘animaux
VE-ascendance+ DGZW
GA Jeunes animaux
VE-CH G vaches, taureaux
VE-Interbull GI taureaux
www.qualitasag.ch | 14
−20 0 20 40 60 80
−20
020
40
60
80
konv. ZW Eiweiss kg 2012
konv.
ZW
Eiw
eis
s k
g 2
016
Korrelation: 0.54
−20 0 20 40 60 80
−20
020
40
60
80
DGZW Eiweiss kg 2012
konv.
ZW
Eiw
eis
s k
g 2
016
Korrelation: 0.7
−20 0 20 40 60 80
−20
020
40
60
80
GOZW Eiweiss kg 2012
konv.
ZW
Eiw
eis
s k
g 2
016
Korrelation: 0.72
Sécurité des valeurs d‘élevagegénomiques
Comparaison VE Proteine kg 2012 - 2016
−20 0 20 40 60 80
−20
020
40
60
80
konv. ZW Eiweiss kg 2012
konv.
ZW
Eiw
eis
s k
g 2
016
Korrelation: 0.54
−20 0 20 40 60 80
−20
020
40
60
80
DGZW Eiweiss kg 2012
konv.
ZW
Eiw
eis
s k
g 2
016
Korrelation: 0.7
−20 0 20 40 60 80
−20
020
40
60
80
GOZW Eiweiss kg 2012
konv.
ZW
Eiw
eis
s k
g 2
016
Korrelation: 0.72
VE-ascendance GOZW
con
v. V
E a
vec
de
sce
nd
ants r = 0.54 r = 0.72
www.qualitasag.ch | 15
Nombre de taureaux dans la populationde référence des Brunes
• Plus la population de référence est grande, plus les valeurs d‘élevage génomiques sont précises
• Vaches dans la population de référence?• Aujourd‘hui presque une population de référence
complète dans la Brune (Projet Intergenomics): env. 6‘500 Taureaux Ekg
Août 2011 Décembre 2011
n Training corr(DGZW,CHZW)n = 250
n Training corr(DGZW,CHZW)n = 360
Changement(%)
Mkg 2471 0.60 3300 0.65 + 4.7
Fkg 2162 0.60 3202 0.70 + 10.6
Ekg 1710 0.53 3254 0.65 + 11.2
ZZ 2188 0.70 2896 0.70 ± 0.0
www.qualitasag.ch | 16
Nombre de taureaux dans la population de référencedes Holstein au niveau mondial, 2 grands „Blocs“
Pourquoi est-ce que la Suisse a eu pendant longtempspas accès?
• Petites populations ne sont pas intéressantes
• Accès ouvert aux génotypes des taureaux étaitgênant
CDDR (élargi) EuroGenomics
USA France
Canada Allemagne
Italie Les Pays-Bas
La Grande-Bretagne Les Etats du Nord
Suisse (depuis 2016) Espagne
Pologne
www.qualitasag.ch | 17
• CDDR (Cooperative Dairy DNA Repository)
– Genotypes-Pool des IA d‘USA & CAN
• Premier échange en février 2016
– SNPs de 125‘000 taureaux HOL ont été obtenus
– 260‘000 animaux dans le pedigree sontrépertoriés
– 14 puces (chip) SNP différentes
– SNPs de 6000 taureaux HO/RH ont été livrés
– Mise à jour mensuel
– Nouveaux taureaux génotypisés
Echange de génotypes Holstein
www.qualitasag.ch | 18
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−40 −20 0 20 40 60 80
−40
−2
00
20
40
60
80
DGZW ORG vs Wonderment
DGZWs ORG
DG
ZW
s W
on
derm
en
t
Mean24.82
Stdv
15.41
Mean
24.69
Stdv
15.4
Korrelation: 1Rangkorrelation: 1
DGZW (Estimation effet SANS taureau XY)
DG
ZW
(E
stim
atio
ne
ffe
tA
VE
Cta
ure
auX
Y) Taureau XY lui-même
Descendants
Petits-fils
Composition de la population de référence (Ex. BV Training avec/ sanstaureau XY)
Rapport plus étroitentre la population de référence et les candidats de sélection!
Population de référence - Sélection
www.qualitasag.ch | 19
Pour résumer:Génotypes sont un miroirde la population
Simmental a peu de liensavec la population de référence:Validation insuffisantepour beaucoup de critères
Structure population de référence(HO/SI)
www.qualitasag.ch | 20
• Brune orginiale fonctionne avec unepopulation de référence mélangée (avecBV/BS)– Taureau max. 95% BS – Vache avec pourcentage OB > 50% augmente la
sécurité
• Simmental: seulement lait + cellules (VE-ITB), autres critères/viande en développement
• Augmentation du nombre de SNP‘s (50‘000 800‘000) n‘augmente pas la sécurité
Sélection génomiquepour les petites populations
www.qualitasag.ch | 21
X X XFaisabilité Limousin
Nombre de taureaux Limousin avec une sécuritépour valeur d‘élevage > 50% et avec ADN actuellement (contrôle ascendance)
• Qualité de l‘ADN doit être en ordre• Population de référence avec 1’500 taureaux
= Investissement CHF 150’000.-
www.qualitasag.ch | 22
Faisabilité Angus
X X XXX
Nombre de taureaux Angus avec une sécuritépour valeur d‘élevage > 50% et avec ADN actuellement (contrôle ascendance)
www.qualitasag.ch | 23
Collaboration internationale
• Seulement avec un modèle Win – Win
• Coopération internationale importante(Interbeef, Echange de génotypes)
• Pays/population spécifiqueAdaptations/développement nécessaire
• Défi: nouvelle méthode pour les racesavec de petits effectifs sont nécessaire
• Commercialisation de phénotypes, génotypes et méthodes
• Plus les investissements sont „opaques“ dans unprogramme d‘élevage, plus grand est l‘intérêt des investisseurs entreprises commerciales avec l‘élevage
www.qualitasag.ch | 24
Un plus grand progrès génétique...
• Puisque la sécurité des valeurs d‘élevage est plus précise (surtout les jeunes animaux) et unintervalle entre générations plus court
• Parce que les critères „difficile“ peuvent êtremieux travailler (par ex. fertilité)
• Parce que l‘on peut travailler sur de nouveauxcritères (par ex. Santé du bétail)
Elevage avec la sélection génomique
www.qualitasag.ch | 26
Index total des taureaux provenant de l‘échangede génotypes Holstein
- Index total ISET- Degré de consanguinité F
www.qualitasag.ch | 27
Consanguinité
• Dépression de la consanguinité = Moins de performances et de santé
• Apparition de tares héréditaires
• Diminution de la variance génétique = Mise en danger du progrès génétique avenir
www.qualitasag.ch | 28
Optimum genetic contribution
• Optimiser le progrès génétique par uneaugmentation de consanguinité définie
• Recherche des animaux avec des valeursd‘élevage élevées et un degré de parenté bas par rapport à la population
www.qualitasag.ch | 29
Bénéfices supplémentaires
• Contrôle d‘ascendance pour les races chezVache Mère Suisse AN, BV, DR, LM et SM
• Tares héréditaires/tests supplémentairesBulldog, Gène culardSans corne, couleur
www.qualitasag.ch | 30
Tares héréditaires grâce aux SNP‘s (extrait)
BH1 Embryonaler Fruchttod BS
BH2 Lebensschwache Kälber BS,FV
CD Durchfall HO
FH1 Zwergwuchs FV
FH2 Minderwuchs (Leberproblem) FV, OB
FH4 Embryonaler Fruchttod FV
FH5 Herzschwäche, Tod innert 48h pp FV
HH1 Embryonaler Fruchttod HO
HH2 Embryonaler Fruchttod HO
HH3 Embryonaler Fruchttod HO
HH4 Embryonaler Fruchttod HO
HH5 Embryonaler Fruchttod HO
JH1 Embryonaler Fruchttod JE
MH1 Embryonaler Fruchttod MO
MH2 Embryonaler Fruchttod MO
Embryonaler Fruchttod = mort de l‘embryon
Lebensschwache Kälber= veau manquant de vitalité
Durchfall = diarrhée
Zwergwuchs = nanisme
Herzschwäche = insuffisance cardiaque
www.qualitasag.ch | 31
Strategie avec les tares héréditaires
• Beaucoup de nouvelles tares héréditairesdécouvertes
• Nouvelles stratégies indispensables
– Exclusion d‘animaux porteurs n‘est pasraisonable
– Evitement d‘accouplement entre animalporteur x animal porteur (Faisabilité avecsaillie?)
– Genetic Load Index (fréquences, dommages, hérédité)
www.qualitasag.ch | 32
ChipNom
GGPLD v2 (9K)
GGPLD v3 (26K)
GGPLDv4 (30K)
50Kv1 (54K)
50Kv2 (54K)
GGPHD (80K)
GGPHD (150K)
HD (850K)
GGPLD v2 (9K)
8.762 92.9% 92.9% 92.6% 92.3% 92.1% 93.6% 95.8%
GGPLD v3 (26K)
26.151 99.8% 32.1% 31.9% 36.3% 95.0% 98.8%
GGPLD v4 (30K)
30.125 34.1% 35.9% 95.1% 97.2%
50K v1 (54K)
54.001 96.6% 52.4% 77.2% 90.2%
50K v2 (54K)
54.609 51.7% 75.8% 90.5%
GGPHD (80K)
76.999 95.9% 96.8%
GGPHD(150K)
139.481 96.3%
HD(850K)
777.962
Modèle puce (chip) SNP – Recouvrement
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IMPUTING = Remplir les SNPs manquantes des animauxgénotypés avec un puce LDSource d‘informations:
– Pedigree
– Information de la population (Linkage Disequilibrium)
Imputing: données
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Moyenne
% correct
Moyenne
% pas correct
Moyenne
correlation
imputé-vrai
Parents 98,6 1,4 0,98
Taureau + MGP 98,1 1,9 0,97
Taureau 97,6 2,4 0,96
Autres 97,3 2,7 0,95
Imputing LD par rapport 50k
Données: 3‘738 avec 50k animaux BV génotypisés
Hypothèse: les 723 jeunes animaux sont génotypisés avecla puce LD
Question: Quelle est la qualité de l‘estimation des SNPs manquantes?
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Génotypes par rapport aux mandataires
0
1000
2000
3000
4000
5000
BVCH SHZV shb weitere
2011 2012
2013 2014
2015 2016
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Nombre de génotypes 2016
5679
1028 66
GGP LD
GGP HD
HD
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Prix du labor pour les puces (Chip) chezGeneSeek
• GGPLDv4 (30K) $ 38.00• 50Kv2 (54K) $ 85.00• GGPHD (150K) $ 85.00• HD (770K) $ 165.00
Prix pour le génotypage aini que le traitement ADN
• Traitement des échantillons Qualitas CHF 5.- bis 17.-
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Par concurrence / consommateur exigés!
• Santé, système immunitaire
• Conversion du fourrage, efficacité, émissions de gaz à effet de serre
• Bien-être des animaux, Comportement
• Qualité de la viande
La sélection génomique permet une disponibilitéplus rapide!
Sélection génomique pour les nouveauxcritères
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• Nouveaux concepts pour les performances
• Exploitations de testage Exploitations souscontrat avec des données fiables pour les critèresintéressant dans l‘élevage
• Génotypage de femelles
– Plus de 1000 vaches avec de bons phénotypes
• Hauts investissements pour les éleveurs
– Coopération internationale
Sélection génomique pour les nouveauxcritères
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Hauts investissements & augmentation de la commercialisation
• Développement de la population de référence / Problème de la grandeur de celle-ci / Propriété & Droit d‘utilisation des données SNP
• Combinaison de la sélection génomique – et des technologiesd‘insémination (Stations ET & doses sexées)
• Nouvelles technologies: édition du génome
• Doses des taureaux au Top sont uniquement en tant que sexésdisponibles
• Les top-femmes appartiennent à des entreprises commerciales
• Index génomique commercial(CLARIFIDE Plus; EvaLim)
Tendances dans l‘élevage bovin
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• Sélection génomique fonctionne et est une partiedu programme de sélection dans le laitier
• Développement de la sélection génomiquecontinue, il y a encore beaucoup à faire
• Nouveaux critères (Fitness, santé, efficacité) gagnent en importance
• Augmentation de la commercialisation du bétaillaitier
• Les races à viande peuvent profiter de l‘expérience dans le domaine laitier
Conclusion
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