A nonsense mutation in the COL7A1 gene causes epidermolysis bullosa in Vorderwald cattle

• DOI: 10.1186/s12863-016-0458-2
• Publication Date: 2016-12-01T04:59:11Z
• Authors: Hubert Pausch; Simon Ammermüller; Christine Wurmser; Henning Hamann; Jens Tetens; Cord Drögemüller; Ruedi Fries
• Keywords: Male; 0301 basic medicine; Collagen Type VII; Epidermolysis bullosa; COL7A1; Nonsense mutation; Skin disease; Autosomal recessive; Autosomal recessive; Cattle Diseases; 610 Medicine & health; Skin disease; Polymorphism, Single Nucleotide; 03 medical and health sciences; Genetics; Animals; COL7A1; Genetics(clinical); Genetic Predisposition to Disease; Epidermolysis bullosa; info:eu-repo/classification/ddc/570; 2. Zero hunger; 0303 health sciences; 630 Agriculture; Nonsense mutation; Sequence Analysis, DNA; Life sciences; ddc:; Pedigree; Codon, Nonsense; 590 Animals (Zoology); 570 Life sciences; biology; Cattle; Female; Epidermolysis Bullosa; Research Article; Genome-Wide Association Study

AbstractBackgroundThe 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.ResultsPedigree analysis indicated autosomal recessive inheritance of epidermolysis bullosa in Vorderwald cattle. We genotyped two diseased and 41 healthy animals at 41,436 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 one diseased calf, three obligate mutation carriers and 1682 healthy animals from various bovine breeds revealed a nonsense mutation (rs876174537, p.Arg1588X) in theCOL7A1gene that segregates with the disease. The same mutation was previously detected in three calves with dystrophic epidermolysis bullosa from the Rotes Hӧehenvieh cattle breed. We show that diseased animals from Vorderwald and Rotes Hӧehenvieh cattle are identical by descent for an 8.72 Mb haplotype encompassing rs876174537 indicating they inherited the deleterious allele from a recent common ancestor.ConclusionsAutosomal recessive epidermolysis bullosa in Vorderwald and Rotes Hӧehenvieh cattle is caused by a nonsense mutation in theCOL7A1gene. 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.