title: Deletion in the EVC2 gene causes chondrodysplastic dwarfism in Tyrolean Grey cattle.
abstract: During the summer of 2013 seven Italian Tyrolean Grey calves were born with abnormally short limbs. Detailed clinical and pathological examination revealed similarities to chondrodysplastic dwarfism. Pedigree analysis showed a common founder, assuming autosomal monogenic recessive transmission of the defective allele. A positional cloning approach combining genome wide association and homozygosity mapping identified a single 1.6 Mb genomic region on BTA 6 that was associated with the disease. Whole genome re-sequencing of an affected calf revealed a single candidate causal mutation in the Ellis van Creveld syndrome 2 (EVC2) gene. This gene is known to be associated with chondrodysplastic dwarfism in Japanese Brown cattle, and dwarfism, abnormal nails and teeth, and dysostosis in humans with Ellis-van Creveld syndrome. Sanger sequencing confirmed the presence of a 2 bp deletion in exon 19 (c.2993_2994ACdel) that led to a premature stop codon in the coding sequence of bovine EVC2, and was concordant with the recessive pattern of inheritance in affected and carrier animals. This loss of function mutation confirms the important role of EVC2 in bone development. Genetic testing can now be used to eliminate this form of chondrodysplastic dwarfism from Tyrolean Grey cattle.
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Murgiano
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: Vidhya
authors.initials: V
authors.lastname: Jagannathan
authors.affiliation: Department of Veterinary Medical Sciences, University of Bologna, Ozzano dell'Emilia, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Benazzi
authors.affiliation: Department of Veterinary Medical Sciences, University of Bologna, Ozzano dell'Emilia, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Bolcato
authors.affiliation: Department of Veterinary Medical Sciences, University of Bologna, Ozzano dell'Emilia, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Brunetti
authors.affiliation: Department of Veterinary Medical Sciences, University of Bologna, Ozzano dell'Emilia, Italy.
authors.forename: Luisa Vera
authors.initials: LV
authors.lastname: Muscatello
authors.affiliation: Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand.
authors.forename: Keren
authors.initials: K
authors.lastname: Dittmer
authors.affiliation: Servizio Veterinario dell'Azienda Sanitaria dell'Alto Adige, Bozen, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Piffer
authors.affiliation: Department of Veterinary Medical Sciences, University of Bologna, Ozzano dell'Emilia, Italy.
authors.forename: Arcangelo
authors.initials: A
authors.lastname: Gentile
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: Cord
authors.initials: C
authors.lastname: Drögemüller
mesh_terms: D000818:Animals; D001483:Base Sequence; D002417:Cattle / Q000235:genetics; D004613:Ellis-Van Creveld Syndrome / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005808:Genes, Recessive; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D016678:Genome; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007558:Italy; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D011506:Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: C473310:EVC2 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011506:Proteins
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