Deletion in the EVC2 gene causes chondrodysplastic dwarfism in Tyrolean Grey cattle. TG954

During summer 2013 in the Italian Tyrolean Grey cattle population seven calves born with abnormally short limbs were reported. Detailed clinical and pathological examination revealed similarities to forms of bovine chondrodysplastic dwarfism. Pedigree analysis showed a common founder assuming an autosomal monogenic recessive transmission of the defect allele. A positional cloning approach combining genome wide association and homozygosity mapping identified a single 1.6 Mb genomic region on BTA 6 associated with the disease. Whole genome re-sequencing of an affected calf was applied to detect a single candidate causal mutation in the Ellis van Creveld syndrome 2 (EVC2) gene, known to be associated with chondrodysplastic dwarfism in Japanese Black cattle and dwarfism, abnormal nails and teeth, and dysostosis in Ellis van Creveld syndrome affected humans. Sanger sequencing confirmed the presence of a 2 bp deletion in exon 19 (c.2993_2994ACdel) leading to a premature stop codon in the coding sequence of bovine EVC2 perfectly associated with the disease. This loss of function mutation confirms the important role of EVC2 during the development of bones. Genetic testing can now be used to eliminate chondrodysplastic dwarfism from Tyrolean Grey cattle.