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Abstract Background Genome-wide association studies (GWAS) were performed at the sequence level to identify candidate mutations that affect the expression of six major milk proteins in Montbéliarde (MON), Normande (NOR), and Holstein (HOL) dairy cattle. Whey protein (α-lactalbumin and β-lactoglobulin) and casein (αs1, αs2, β, and κ) contents were estimated by mid-infrared (MIR) spectrometry, with medium to high accuracy (0.59 ≤ R2 ≤ 0.92), for 848,068 test-day milk samples from 156,660 cows in the first three lactations. Milk composition was evaluated as average test-day measurements adjusted for environmental effects. Next, we genotyped a subset of 8080 cows (2967 MON, 2737 NOR, and 2306 HOL) with the BovineSNP50 Beadchip. For each breed, genotypes were first imputed to high-density (HD) using HD single nucleotide polymorphisms (SNPs) genotypes of 522 MON, 546 NOR, and 776 HOL bulls. The resulting HD SNP genotypes were subsequently imputed to the sequence level using 27 million high-quality sequence variants selected from Run4 of the 1000 Bull Genomes consortium (1147 bulls). Within-breed, multi-breed, and conditional GWAS were performed. Results Thirty-four distinct genomic regions were identified. Three regions on chromosomes 6, 11, and 20 had very significant effects on milk composition and were shared across the three breeds. Other significant effects, which partially overlapped across breeds, were found on almost all the autosomes. Multi-breed analyses provided a larger number of significant genomic regions with smaller confidence intervals than within-breed analyses. Combinations of within-breed, multi-breed, and conditional analyses led to the identification of putative causative variants in several candidate genes that presented significant protein–protein interactions enrichment, including those with previously described effects on milk composition (SLC37A1, MGST1, ABCG2, CSN1S1, CSN2, CSN1S2, CSN3, PAEP, DGAT1, AGPAT6) and those with effects reported for the first time here (ALPL, ANKH, PICALM). Conclusions GWAS applied to fine-scale phenotypes, multiple breeds, and whole-genome sequences seems to be effective to identify candidate gene variants. However, although we identified functional links between some candidate genes and milk phenotypes, the causality between candidate variants and milk protein composition remains to be demonstrated. Nevertheless, the identification of potential causative mutations that underlie milk protein composition may have immediate applications for improvements in cheese-making.

In 2010, a routine genetic evaluation on occurrence of clinical mastitis in three main dairy cattle breeds – Montbéliarde (MO), Normande (NO) and Holstein (HO) – was implemented in France. Records were clinical mastitis events reported by farmers to milk recording technicians and the analyzed trait was the binary variable describing the occurrence of a mastitis case within the first 150 days of the first three lactations. Genetic parameters of clinical mastitis were estimated for the three breeds. Low heritability estimates were found: between 2% and 4% depending on the breed. Despite its low heritability, the trait exhibits genetic variation so efficient genetic improvement is possible. Genetic correlations with other traits were estimated, showing large correlations (often>0.50, in absolute value) between clinical mastitis and somatic cell score (SCS), longevity and some udder traits. Correlation with milk yield was moderate and unfavorable (ρ=0.26 to 0.30). High milking speed was genetically associated with less mastitis in MO (ρ=−0.14) but with more mastitis in HO (ρ=0.18). A two-step approach was implemented for routine evaluation: first, a univariate evaluation based on a linear animal model with permanent environment effect led to pre-adjusted records (defined as records corrected for all non-genetic effects) and associated weights. These data were then combined with similar pre-adjusted records for others traits in a multiple trait BLUP animal model. The combined breeding values for clinical mastitis obtained are the official (published) ones. Mastitis estimated breeding values (EBV) were then combined with SCSs EBV into an udder health index, which receives a weight of 14.5% to 18.5% in the French total merit index (ISU) of the three breeds. Interbull genetic correlations for mastitis occurrence were very high (ρ=0.94) with Nordic countries, where much stricter recording systems exist reflecting a satisfactory quality of phenotypes as reported by the farmers. They were lower (around 0.80) with countries supplying SCS as a proxy for the international evaluation on clinical mastitis.

Hérité de la loi sur l’Élevage de 1966, le dispositif génétique français a permis la mise en place d’un vaste recueil de phénotypes en ferme et en station. Toutes ces collectes ont pu être valorisées collectivement au travers de nombreuses évaluations génétiques, et notamment les évaluations nationales sur les données recueillies en ferme appelées « IBOVAL ». Ces évaluations ont évolué tant d'un point de vue méthodologique (évaluations polygéniques et maintenant génomiques) que sur l’éventail des caractères valorisés. La filière de production de viande bovine dispose aujourd’hui d’outils génétiques performants permettant d’évaluer les reproducteurs bovins allaitants, de les sélectionner sur leurs aptitudes bouchères et leur qualités maternelles en ferme et en station (contrôle individuel ou sur descendance). Le panel de caractères traités (naissance, sevrage, post-sevrage, reproduction, aptitudes bouchères) permet d’élaborer des objectifs de sélection adaptés aux orientations raciales, aux contraintes de la filière et de l’élevage. Les programmes de sélection utilisant ces outils génèrent un progrès génétique. Celui-ci est diffusé efficacement, même si la faible pénétration de l’insémination animale reste un facteur limitant. Enfin, l’arrivée de la génomique, les changements organisationnels induits par le nouveau règlement zootechnique européen et le contexte difficile de l’élevage vont entraîner des évolutions au niveau des outils et des objectifs de sélection.

Cette étude présente les principaux résultats d’estimation de paramètres génétiques et de détection de QTL obtenus dans le cadre du programme PhénoFinlait sur les caractères de composition en Acides Gras (AG) et protéines du lait dans trois races bovines (Holstein, Montbéliarde et Normande), deux races ovines (Lacaune et Manech Tête Rousse) et deux races caprines (Alpine et Saanen). La composition du lait est estimée à partir de la spectrométrie dans le moyen infrarouge. Les paramètres génétiques sont estimés à partir des données de 102 000 contrôles laitiers de 22 000 vaches en première lactation, 67 000 contrôles de 20 000 brebis, et 45 000 contrôles de 13 700 chèvres. Ils sont très homogènes entre espèces et entre races. En revanche, ils dépendent beaucoup du mode d’expression des caractères, exprimés en proportion du lait ou de la matière. Exprimés en teneur dans le lait, les AG saturés présentent une héritabilité plus élevée que les insaturés chez les bovins et les ovins, mais l’écart est plus faible quand ils sont exprimés en teneur dans le gras. Chez les caprins, les estimations d’héritabilité sont plus élevées pour les caractères exprimés en teneur dans la matière grasse. Les mesures d’AG sont fortement corrélées entre stades de lactation, à l’exception du premier mois qui apparaît comme un caractère assez différent. Les corrélations génétiques sont positives entre AG saturés et entre AG insaturés. Entre AG saturés et insaturés, les corrélations sont positives pour les AG exprimés en teneur dans le lait mais négatives quand les AG sont exprimés en pourcentage de la matière grasse. Les AG saturés sont très fortement corrélés au taux butyreux du lait. Concernant les protéines, les estimations d’héritabilité sont très élevées pour la bêta-lactoglobuline, assez élevées pour les caséines, plus modérées pour l’alpha-lactalbumine. Concernant les corrélations, il existe une forte analogie entre AG et protéines. Ainsi, les caséines sont fortement corrélées entre elles et fortement liées au taux protéique. Leur corrélation avec les protéines sériques est positive quand les protéines sont exprimées en teneur dans le lait, mais très négatives quand elles sont exprimées en teneur dans les protéines. Les analyses de détection de QTL reposent sur les données de 7 800 vaches, 1 800 brebis et 2 300 chèvres génotypées avec des puces SNP pangénomiques. En moyenne, 9 QTL d’AG ont été détectés par caractère et par race bovine. Les QTL les plus importants ont été trouvés sur les chromosomes 14 (gène DGAT1), 5, 19, 27, 17, 11 et 13. On observe une forte co-localisation de QTL entre AG du même type, reflétant leur origine métabolique commune. Une fraction notable de ces QTL semble partagée entre races. 22 à 29 QTL sont détectés en moyenne pour chaque taux de protéine. Les plus significatifs se situent sur les chromosomes 6 (2 régions QTL, régions des gènes ABCG2 et des caséines), 11 (gène de la bêta-lactoglobuline) et 20 (gène GHR vers 32 Mb, mais aussi vers 58Mb). Le gène DGAT1 affecte également de nombreuses protéines exprimées en teneur dans le lait. Ces résultats indiquent que la composition fine du lait pourrait être modifiée par sélection, même si les grands équilibres entre composants peuvent difficilement être bouleversés. Il est ainsi possible d’augmenter la fraction de caséines dans les protéines. Il est aussi possible d’augmenter la fraction d’AG insaturés dans le lait, mais sans doute au prix d’une diminution du taux butyreux.

Background: Genome-wide association studies (GWAS) were performed at the sequence level to identify candidate mutations that affect the expression of six major milk proteins in Montbéliarde (MON), Normande (NOR), and Holstein (HOL) dairy cattle. Whey protein (α-lactalbumin and β-lactoglobulin) and casein (αs1, αs2, β, and κ) contents were estimated by mid-infrared (MIR) spectrometry, with medium to high accuracy (0.59 ≤ R² ≤ 0.92), for 848,068 test-day milk samples from 156,660 cows in the first three lactations. Milk composition was evaluated as average test-day measurements adjusted for environmental effects. Next, we genotyped a subset of 8080 cows (2967 MON, 2737 NOR, and 2306 HOL) with the BovineSNP50 Beadchip. For each breed, genotypes were first imputed to high-density (HD) using HD single nucleotide polymorphisms (SNPs) genotypes of 522 MON, 546 NOR, and 776 HOL bulls. The resulting HD SNP genotypes were subsequently imputed to the sequence level using 27 million high-quality sequence variants selected from Run4 of the 1000 Bull Genomes consortium (1147 bulls). Within-breed, multi-breed, and conditional GWAS were performed. Results: Thirty-four distinct genomic regions were identified. Three regions on chromosomes 6, 11, and 20 had very significant effects on milk composition and were shared across the three breeds. Other significant effects, which partially overlapped across breeds, were found on almost all the autosomes. Multi-breed analyses provided a larger number of significant genomic regions with smaller confidence intervals than within-breed analyses. Combinations of within-breed, multi-breed, and conditional analyses led to the identification of putative causative variants in several candidate genes that presented significant protein--protein interactions enrichment, including those with previously described effects on milk composition (SLC37A1, MGST1, ABCG2, CSN1S1, CSN2, CSN1S2, CSN3, PAEP, DGAT1, AGPAT6) and those with effects reported for the first time here (ALPL, ANKH, PICALM). Conclusions: GWAS applied to fine-scale phenotypes, multiple breeds, and whole-genome sequences seems to be effective to identify candidate gene variants. However, although we identified functional links between some candidate genes and milk phenotypes, the causality between candidate variants and milk protein composition remains to be demonstrated. Nevertheless, the identification of potential causative mutations that underlie milk protein composition may have immediate applications for improvements in cheese-making. [ABSTRACT FROM AUTHOR]

In 2010, a routine genetic evaluation on occurrence of clinical mastitis in three main dairy cattle breeds – Montbéliarde (MO), Normande (NO) and Holstein (HO) – was implemented in France. Records were clinical mastitis events reported by farmers to milk recording technicians and the analyzed trait was the binary variable describing the occurrence of a mastitis case within the first 150 days of the first three lactations. Genetic parameters of clinical mastitis were estimated for the three breeds. Low heritability estimates were found: between 2% and 4% depending on the breed. Despite its low heritability, the trait exhibits genetic variation so efficient genetic improvement is possible. Genetic correlations with other traits were estimated, showing large correlations (often>0.50, in absolute value) between clinical mastitis and somatic cell score (SCS), longevity and some udder traits. Correlation with milk yield was moderate and unfavorable (ρ =0.26 to 0.30). High milking speed was genetically associated with less mastitis in MO (ρ =−0.14) but with more mastitis in HO (ρ =0.18). A two-step approach was implemented for routine evaluation: first, a univariate evaluation based on a linear animal model with permanent environment effect led to pre-adjusted records (defined as records corrected for all non-genetic effects) and associated weights. These data were then combined with similar pre-adjusted records for others traits in a multiple trait BLUP animal model. The combined breeding values for clinical mastitis obtained are the official (published) ones. Mastitis estimated breeding values (EBV) were then combined with SCSs EBV into an udder health index, which receives a weight of 14.5% to 18.5% in the French total merit index (ISU) of the three breeds. Interbull genetic correlations for mastitis occurrence were very high (ρ =0.94) with Nordic countries, where much stricter recording systems exist reflecting a satisfactory quality of phenotypes as reported by the farmers. They were lower (around 0.80) with countries supplying SCS as a proxy for the international evaluation on clinical mastitis. [ABSTRACT FROM AUTHOR]