TY - JOUR T1 - A nonsense mutation in the <em>COL7A1</em> gene causes epidermolysis bullosa in Vorderwald cattle JF - bioRxiv DO - 10.1101/062968 SP - 062968 AU - Hubert Pausch AU - Simon Ammermüeller AU - Christine Wurmser AU - Henning Hamann AU - Jens Tetens AU - Cord Drögemüller AU - Ruedi Fries Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/07/09/062968.abstract N2 - Background The widespread use of individual sires for artificial insemination promotes the propagation of recessive conditions. Inadvertent matings between unnoticed carriers of deleterious alleles may result in the manifestation of fatal phenotypes in their progeny. Breeding consultants and farmers reported on Vorderwald calves with a congenital skin disease. The clinical findings in affected calves were compatible with epidermolysis bullosa.Results Pedigree analysis indicated autosomal recessive inheritance of epidermolysis bullosa in Vorderwald cattle. We genotyped two diseased and 41 healthy animals at 40,792 single nucleotide polymorphisms and performed whole-genome haplotype-based association testing, which allowed us to map the locus responsible for the skin disease to the distal end of bovine chromosome 22 (P=8.0×10−14). The analysis of whole-genome re-sequencing data of 1686 animals including one diseased calf, three obligate mutation carriers and 1682 healthy animals from various bovine breeds revealed a nonsense mutation (ss1995911272, p.Arg1588X) in the COL7A1 gene that segregates with the disease. The same mutation was previously detected in three calves with dystrophic epidermolysis bullosa from the Rotes Höhenvieh cattle breed. We show that diseased animals from Vorderwald and Rotes Höhenvieh cattle are identical by descent for an 8.72 Mb haplotype encompassing ss1995911272 indicating they inherited the deleterious allele from a recent common ancestor.Conclusions Autosomal recessive epidermolysis bullosa in Vorderwald and Rotes Höhenvieh cattle is caused by a nonsense mutation in the COL7A1 gene. Our findings demonstrate that recessive deleterious alleles may segregate across cattle populations without apparent admixture. The identification of the causal mutation now enables the reliable detection of carriers of the defective allele. Genome-based mating strategies can avoid inadvertent matings of carrier animals thereby preventing the birth of homozygous calves that suffer from a painful skin disease. ER -