ena-STUDY-UNIBE-IG-14-10-2014-17:15:00:361-276
Epidermolysa bullosa in Danish Hereford calves is caused by a deletion in LAMC2 gene
Epidermolysis bullosa (EB) constitutes a heterogeneous group of skin disorders of genetic aetiology that are characterised by skin and mucous membrane blistering and ulceration in response to even minor trauma. Here we report the occurrence of EB in three Danish Hereford cattle from the same herd. Two of the animals showed skin ulcerations covered by crusts stretched proximally from the coronet band to the fetlock region in both hind limb and were also found above the coronet band in the right front limb, in the left lateral metatarsal area and locally in the ventral part of the trunk. In one case, skin lesions were restricted to bilateral absence of horn on the front limb dew claws. Analysis of the family tree indicated that inbreeding and the transmission of a single recessive mutation from a common ancestor could be causative. We genotyped 777,961 SNPs on a single affected calf, its sire and its dam and detected extended homozygous regions containing 8 out of 18 EB candidate genes. We performed whole genome sequencing of one affected calf and called all coding DNA variants. Thereby, we detected a homozygous 2.6 kb deletion encompassing the first exon of the LAMC2 gene. This mutation completely removes the start codon of this gene and is therefore predicted to be completely disruptive. We confirmed the presence of this LAMC2 loss of function mutation in heterozygosity in the available parents. Verifying the homozygous variants present in a candidate gene allowed us to quickly identify the causative mutation and contribute to the final diagnosis of EB in Hereford. Our investigation confirms the role of LAMC2 in EB aetiology and shows the importance of whole genome sequencing in the analysis of rare genetic disease in livestock.
Epidermolysis bullosa (EB) constitutes a heterogeneous group of skin disorders of genetic aetiology that are characterised by skin and mucous membrane blistering and ulceration in response to even minor trauma. Here we report the occurrence of EB in three Danish Hereford cattle from the same herd. Two of the animals showed skin ulcerations covered by crusts stretched proximally from the coronet band to the fetlock region in both hind limb and were also found above the coronet band in the right front limb, in the left lateral metatarsal area and locally in the ventral part of the trunk. In one case, skin lesions were restricted to bilateral absence of horn on the front limb dew claws. Analysis of the family tree indicated that inbreeding and the transmission of a single recessive mutation from a common ancestor could be causative. We genotyped 777,961 SNPs on a single affected calf, its sire and its dam and detected extended homozygous regions containing 8 out of 18 EB candidate genes. We performed whole genome sequencing of one affected calf and called all coding DNA variants. Thereby, we detected a homozygous 2.6 kb deletion encompassing the first exon of the LAMC2 gene. This mutation completely removes the start codon of this gene and is therefore predicted to be completely disruptive. We confirmed the presence of this LAMC2 loss of function mutation in heterozygosity in the available parents. Verifying the homozygous variants present in a candidate gene allowed us to quickly identify the causative mutation and contribute to the final diagnosis of EB in Hereford. Our investigation confirms the role of LAMC2 in EB aetiology and shows the importance of whole genome sequencing in the analysis of rare genetic disease in livestock.