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Abstract Background Nine male and eight female calves born to a Normande artificial insemination bull named “Ly” were referred to the French National Observatory of Bovine Abnormalities for multiple fractures, shortened gestation, and stillbirth or perinatal mortality. Results Using Illumina BovineSNP50 array genotypes from affected calves and 84 half-sib controls, the associated locus was mapped to a 6.5-Mb interval on chromosome 19, assuming autosomal inheritance with germline mosaicism. Subsequent comparison of the whole-genome sequences of one case and 5116 control genomes, followed by genotyping in the affected pedigree, identified a de novo missense substitution within the NC1 domain of the COL1A1 gene (Chr19 g.36,473,965G > A; p.D1412N) as unique candidate variant. Interestingly, the affected residue was completely conserved among 243 vertebrate orthologs, and the same substitution in humans has been reported to cause type II osteogenesis imperfecta (OI), a connective tissue disorder that is characterized primarily by bone deformity and fragility. Moreover, three COL1A1 mutations have been described to cause the same syndrome in cattle. Necropsy, computed tomography, radiology, and histology confirmed the diagnosis of type II OI, further supporting the causality of this variant. In addition, a detailed analysis of gestation length and perinatal mortality in 1387 offspring of Ly and more than 160,000 progeny of 63 control bulls allowed us to statistically confirm in a large pedigree the association between type II OI and preterm delivery, which is probably due to premature rupture of fetal membranes and has been reported in several isolated cases of type II OI in humans and cattle. Finally, analysis of perinatal mortality rates and segregation distortion supported a low level of germ cell mosaicism in Ly, with an estimate of 4.5% to 7.7% of mutant sperm and thus 63 to 107 affected calves born. These numbers contrast with the 17 cases reported and raise concerns about the underreporting of congenital defects to heredo-surveillance platforms, even for textbook genetic syndromes. Conclusions In conclusion, we describe a large animal model for a recurrent substitution in COL1A1 that is responsible for type II OI in humans. More generally, this study highlights the utility of such datasets and large half-sib families available in livestock species to characterize sporadic genetic defects.

Abstract Background Bovine paratuberculosis, or Johne’s disease (JD), is a contagious and incurable disease caused by Mycobacterium avium subsp. paratuberculosis (MAP). It has adverse effects on animal welfare and is very difficult to control, leading to serious economic consequences. An important line of defense to this disease is host genetic resistance to MAP, which, when it will be more fully understood, could be improved through selective breeding. Using a large dataset of Holstein cows (161,253 animals including 56,766 cows with ELISA serological phenotypes and 12,431 animals with genotypes), we applied a single-step single nucleotide polymorphism (SNP) best linear unbiased prediction approach to investigate the genetic determinism underlying resistance to this disease (heritability estimate and identification of relevant genomic regions) and estimated genetic trends, reliability, and relative risk factors associated with genomic predictions. Results Resistance to JD was moderately heritable (0.14) and 16 genomic regions were detected that accounted for at least 0.05% of the breeding values variance (GV) in resistance to JD, and were located on chromosomes 1, 3, 5, 6, 7, 19, 20, 21, 23, 25, and 27, with the highest percentage of variance explained by regions on chromosomes 23 (0.36% GV), 5 (0.22% GV), 1 (0.14% GV), and 3 (0.13% GV). When estimated for the whole chromosomes, the autosomes with the largest overall contributions were chromosomes 3 (5.3% GV), 10 (4.8%), 23 (4.7%), 1 (3.6%), 7 (3.4%), 5 (2.9%), 12 (2.5%), 11 (2.2%), and 13 (2%). We estimated a slightly favorable genetic trend in resistance to JD over the last two decades, which can be explained by a low positive genetic correlation between resistance to JD and total merit index (+ 0.06). Finally, in a validation population of 907 cows, relatively reliable genomic predictions (reliability = 0.55) were obtained, which allowed the identification of cows at high risk of infection. Conclusions This study provides new insights into the genetic determinism of resistance to JD and shows that this trait can be predicted from SNP genotypes. It has led to the implementation of a single-step genomic evaluation that should rapidly become an effective tool for controlling paratuberculosis on French Holstein farms.

Abstract Background Bovine paratuberculosis is a contagious disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), with adverse effects on animal welfare and serious economic consequences. Published results on host genetic resistance to MAP are inconsistent, mainly because of difficulties in characterizing the infection status of cows. The objectives of this study were to identify quantitative trait loci (QTL) for resistance to MAP in Holstein and Normande cows with an accurately defined status for MAP. Results From MAP-infected herds, cows without clinical signs of disease were subjected to at least four repeated serum ELISA and fecal PCR tests over time to determine both infected and non-infected statuses. Clinical cases were confirmed using PCR. Only cows that had concordant results for all tests were included in further analyses. Positive and control cows were matched within herd according to their birth date to ensure a same level of exposure to MAP. Cows with accurate phenotypes, i.e. unaffected (control) or affected (clinical or non-clinical cases), were genotyped with the Illumina BovineSNP50 BeadChip. Genotypes were imputed to whole-genome sequences using the 1000 Bull Genomes reference population (run6). A genome-wide association study (GWAS) of MAP status of 1644 Holstein and 649 Normande cows, using either two (controls versus cases) or three classes of phenotype (controls, non-clinical and clinical cases), revealed three regions, on Bos taurus (BTA) chromosomes 12, 13, and 23, presenting significant effects in Holstein cows, while only one of those was identified in Normande cows (BTA23). The most significant effect was found on BTA13, in a short 8.5-kb region. Conditional analyses revealed that only one causal variant may be responsible for the effects observed on each chromosome with the ABCC4 (BTA12), CBFA2T2 (BTA13), and IER3 (BTA23) genes as good functional candidates. Conclusions A sequence-based GWAS on cows for which resistance to MAP was accurately defined, was able to identify candidate variants located in genes that were functionally related to resistance to MAP; these explained up to 28% of the genetic variance of the trait. These results are very encouraging for efforts towards implementation of a breeding strategy aimed at improving resistance to paratuberculosis in Holstein cows.

Les nouvelles technologies des capteurs, de la communication et du traitement des données ont fait leur entrée dans les élevages. Elles constituent une nouvelle source d’informations à la fois plus nombreuses et diversifiées, à plus haute fréquence, sur des durées plus longues et pour plus d’entités. Elles soulèvent dans le même temps des problèmes de qualification, de fiabilité et de maintenance des informations qui restent largement à explorer. Dans la théorie de la décision, le terme information ne concerne que ce qui est susceptible d’avoir un impact sur la décision. Lorsque les informations acquises par des dispositifs automatiques se substituent à des informations obtenues par des activités de surveillance ou de mesure manuelles, ces dispositifs trouvent rapidement leur place s’ils sont fiables. À l’opposé, pour d’autres informations concernant les alertes de santé, le bien-être ou l’environnement, les dispositifs sont encore peu utilisés et leur intégration dans des outils performants d’aide à la décision est encore insuffisante. De plus, aujourd’hui, l’information sort du cadre strict de l’élevage. Les consommateurs veulent savoir d’où vient leur aliment, comment il a été produit, dans quel respect de l’environnement ou du bien-être animal, avec des garanties sur ces informations. En conclusion, les nouvelles technologies de l’information permettent l’accès à beaucoup de nouvelles informations en élevage, mais avec une idée encore trop imprécise de leurs utilisations dans les processus de décision de l’éleveur ou d’autres acteurs.