BackgroundCongenital skeletal malformations represent a heterogeneous group of disorders affecting bone and cartilage development. In cattle, particular chondrodysplastic forms have been identified in several miniature breeds. In this study, a phenotypic characterization was performed of an affected Miniature Zebu calf using computed tomography, necropsy and histopathological examinations, whole genome sequencing of the case and its parents on an Illumina NextSeq 500 in 2 × 150 bp paired-end mode and validation using Sanger sequencing and a Kompetitive Allele Specific PCR assay. Samples from the family of an affected Miniature Zebu with bulldog syndrome including parents and siblings, 42 healthy Miniature Zebu not related with members of the herd and 88 individuals from eight different taurine cattle breeds were available for validation.ResultsA bulldog-like Miniature Zebu calf showing a large bulging head, a short and compressed body and extremely short and stocky limbs was delivered after a fetotomy. Computed tomography and necropsy revealed severe craniofacial abnormalities including a shortening of the ventral nasal conchae, a cleft hard palate, rotated limbs as well as malformed and fused vertebrae and ribs. Histopathologic examination showed a disorganization of the physeal cartilage with disorderly arranged chondrocytes in columns and a multifocal closed epiphyseal plate. Whole-genome sequencing of this malformed Miniature Zebu calf, its dam and sire and subsequent comparative sequence analysis revealed a one base pair insertion (ACAN:c.5686insC) located within the cartilage development gene aggrecan (ACAN) exclusively homozygous in the affected calf and heterozygous in its parents. This variant was predicted to cause a frameshift (p.Val1898fsTer9) and thus a truncation of the chondroitin sulfate domain as well as a loss of the C-terminal globular domain of ACAN. It perfectly co-segregated with the lethal bulldog syndrome in Miniature Zebus.ConclusionsWe found a novel mutation in ACAN causing a recessive lethal chondrodysplasia in Miniature Zebu cattle. A diagnostic test for this mutation is now available for Miniature Zebu breeders preventing further cases of bulldog syndrome by targeted matings. To the authors’ best knowledge, this is the first case of a Miniature Zebu associated with an ACAN mutation.Electronic supplementary materialThe online version of this article (10.1186/s12863-018-0678-8) contains supplementary material, which is available to authorized users.

Cataracts are focal to diffuse opacities of the eye lens causing impaired vision or complete blindness. For bilateral congenital cataracts in Red Holsteins a perfectly cosegregating mutation within the CPAMD8 gene (CPAMD8:g.5995966C>T) has been reported. We genotyped the CPAMD8:g.5995966C>T variant in Holstein calves affected by congenital bilateral congenital cataracts, their unaffected relatives and randomly selected herd mates. Ophthalmological examinations were performed in all affected individuals to confirm a congenital cataract. Whole genome sequencing was employed to screen variants in candidate genes for the Morgagnian cataract phenotype. In the present study, 3/35 cases were confirmed as homozygous mutated and 6/14 obligate carriers. Further 7/46 unaffected animals related with these cases were heterozygous mutated for the CPAMD8:g.5995966C>T variant. However 32 cases with a congenital cataract showed the wild type for the CPAMD8 variant. We did not identify variants in the candidate genes CPAMD8 and NID1 or in their close neighborhood as strongly associated with the congenital cataract phenotype in Holstein calves with the CPAMD8 wild type. In conclusion, the CPAMD8:g.5995966C>T variant is insufficient to explain the majority of Morgagnian congenital cataract phenotypes in Holsteins. It is very likely that congenital bilateral cataracts may be genetically heterogeneous and not yet known variants in genes other than CPAMD8 and NID1 are involved.

Background: Munchkin cats were founded on a naturally occurring mutation segregating into long-legged and short-legged types. Short-legged cats showed disproportionate dwarfism (chondrodysplasia) in which all four legs are short and are referred as standard Munchkin cats. Long-legged animals are referred as non-standard Munchkin cats. A previous study using genome-wide single nucleotide polymorphisms (SNPs) for genome-wide association analysis identified a significantly associated region at 168-184 Mb on feline chromosome (FCA) B1. Results: In this study, we validated the critical region on FCA B1 using a case-control study with 89 cats and 14 FCA B1-SNPs. A structural variant within UGDH (NC_018726.2:g.173294289_173297592delins108, Felis catus 8.0, equivalent to NC_018726.3:g.174882895_174886198delins108, Felis catus 9.0) on FCA B1 was perfectly associated with the phenotype of short-legged standard Munchkin cats. Conclusion: This UGDH structural variant very likely causes the chondrodysplastic (standard) phenotype in Munchkin cats. The lack of homozygous mutant phenotypes and reduced litter sizes in standard Munchkin cats suggest an autosomal recessive lethal trait in the homozygote state. We propose an autosomal dominant mode of inheritance for the chondrodysplastic condition in Munchkin cats.

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Footrot is one of the major causes of lameness in sheep and leads to decreased animal welfare and high economic losses. The causative agent is the Gram-negative anaerobic bacterium Dichelobacter nodosus. The prevalence of D. nodosus in 207 sheep flocks across Germany was 42.9%. Based on the sequence variation in the type IV fimbrial gene fimA, D. nodosus can be subdivided into ten serogroups (A–I and M). There are commercially available vaccines covering nine serogroups, but the efficacy is low compared to bivalent vaccines. The aim of this study was to investigate the diversity of serogroups in Germany at the flock and animal levels. In total, we detected at least one serogroup in 819 samples out of 969 D. nodosus-positive samples from 83 flocks using serogroup-specific singleplex PCR for the serogroups A–I. Serogroup A was most prevalent at the animal level, followed by serogroups B, H and C. At the flock level, serogroups A and B had the highest prevalence, each with 64%, but only 40% of flocks had both. The average number of serogroups per animal was 1.42 (range one to five) and, per flock, 3.10 (range one to six). The serogrouping showed within-flock specific clusters but were widely distributed, with 50 different combinations across the flocks. The factors associated with the number of serogroups per animal and single serogroups were the load of D. nodosus, footrot score, sheep breed and flock. Our results indicate that efficient vaccination programs would benefit from tailor-made flock-specific vaccines and regular monitoring of circulating serotypes in the flock to be able to adjust vaccine formulations for nationwide progressive control of footrot in Germany.