title: Epidermolysis bullosa in Danish Hereford calves is caused by a deletion in LAMC2 gene.
abstract: BACKGROUND
  Heritable forms of epidermolysis bullosa (EB) constitute 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 one herd.
  
  
  RESULTS
  Two of the animals were necropsied and showed oral mucosal blistering, skin ulcerations and partly loss of horn on the claws. Lesions were histologically characterized by subepidermal blisters and ulcers. Analysis of the family tree indicated that inbreeding and the transmission of a single recessive mutation from a common ancestor could be causative. We performed whole genome sequencing of one affected calf and searched all coding DNA variants. Thereby, we detected a homozygous 2.4 kb deletion encompassing the first exon of the LAMC2 gene, encoding for laminin gamma 2 protein. This loss of function mutation completely removes the start codon of this gene and is therefore predicted to be completely disruptive. The deletion co-segregates with the EB phenotype in the family and absent in normal cattle of various breeds. Verifying the homozygous private variants present in candidate genes allowed us to quickly identify the causative mutation and contribute to the final diagnosis of junctional EB in Hereford cattle.
  
  
  CONCLUSIONS
  Our investigation confirms the known role of laminin gamma 2 in EB aetiology and shows the importance of whole genome sequencing in the analysis of rare diseases in livestock.
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, CH-3001, Bern, Switzerland. lmurgiano@gmail.com.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Murgiano
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, CH-3001, Bern, Switzerland. natalie.wiedemar@vetsuisse.unibe.ch.
authors.forename: Natalie
authors.initials: N
authors.lastname: Wiedemar
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, CH-3001, Bern, Switzerland. vidhya.jagannathan@vetsuisse.unibe.ch.
authors.forename: Vidhya
authors.initials: V
authors.lastname: Jagannathan
authors.affiliation: Department of Veterinary Disease Biology, Section for Veterinary Pathology, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 3, DK-1870, Frederiksberg C, Denmark. louise.isling@gmail.com.
authors.forename: Louise K
authors.initials: LK
authors.lastname: Isling
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, CH-3001, Bern, Switzerland. cord.droegemueller@vetsuisse.unibe.ch.
authors.forename: Cord
authors.initials: C
authors.lastname: Drögemüller
authors.affiliation: Department of Veterinary Disease Biology, Section for Veterinary Pathology, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 3, DK-1870, Frederiksberg C, Denmark. jager@sund.ku.dk.|Department of Large Animal Sciences, Section for Veterinary Reproduction and Obstetrics, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlaegevej 68, DK-1870, Frederiksberg C, Denmark. jager@sund.ku.dk.
authors.forename: Jørgen S
authors.initials: JS
authors.lastname: Agerholm
mesh_terms: D000818:Animals; D002417:Cattle / Q000235:genetics; D002418:Cattle Diseases / Q000235:genetics* / Q000473:pathology; D004820:Epidermolysis Bullosa / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D005260:Female; D017353:Gene Deletion; D016678:Genome / Q000235:genetics; D060005:Genotyping Techniques / Q000662:veterinary; D049690:History, Ancient; D006720:Homozygote; D007797:Laminin / Q000235:genetics* / Q000502:physiology; D010375:Pedigree; D012867:Skin / Q000473:pathology
chemical_list: D007797:Laminin