title: A stop-gain in the laminin, alpha 3 gene causes recessive junctional epidermolysis bullosa in Belgian Blue cattle.
abstract: Four newborn purebred Belgian Blue calves presenting a severe form of epidermolysis bullosa were recently referred to our heredo-surveillance platform. SNP array genotyping followed by autozygosity mapping located the causative gene in a 8.3-Mb interval on bovine chromosome 24. Combining information from (i) whole-genome sequencing of an affected calf, (ii) transcriptomic data from a panel of tissues and (iii) a list of functionally ranked positional candidates pinpointed a private G to A nucleotide substitution in the LAMA3 gene that creates a premature stop codon (p.Arg2609*) in exon 60, truncating 22% of the corresponding protein. The LAMA3 gene encodes the alpha 3 subunit of the heterotrimeric laminin-332, a key constituent of the lamina lucida that is part of the skin basement membrane connecting epidermis and dermis layers. Homozygous loss-of-function mutations in this gene are known to cause severe junctional epidermolysis bullosa in human, mice, horse, sheep and dog. Overall, our data strongly support the causality of the identified gene and mutation.
authors.affiliation: Bovine Clinic, FARAH and Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Sartelet
authors.affiliation: Unit of Animal Genomics, GIGA-R and Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
authors.forename: Chad
authors.identifier: http://orcid.org/0000-0002-6268-0107
authors.initials: C
authors.lastname: Harland
authors.affiliation: Unit of Animal Genomics, GIGA-R and Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
authors.forename: Nico
authors.initials: N
authors.lastname: Tamma
authors.affiliation: Unit of Animal Genomics, GIGA-R and Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.|GIGA-Genomic platform, University of Liège, Liège, Belgium.
authors.forename: Latifa
authors.initials: L
authors.lastname: Karim
authors.affiliation: Department of Pathology, FARAH and Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
authors.forename: Calixte
authors.initials: C
authors.lastname: Bayrou
authors.affiliation: Bovine Clinic, FARAH and Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
authors.forename: Wanbo
authors.initials: W
authors.lastname: Li
authors.affiliation: Unit of Animal Genomics, GIGA-R and Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.|GIGA-Genomic platform, University of Liège, Liège, Belgium.
authors.forename: Naima
authors.initials: N
authors.lastname: Ahariz
authors.affiliation: Unit of Animal Genomics, GIGA-R and Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.|GIGA-Genomic platform, University of Liège, Liège, Belgium.
authors.forename: Wouter
authors.initials: W
authors.lastname: Coppieters
authors.affiliation: Unit of Animal Genomics, GIGA-R and Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Georges
authors.affiliation: Unit of Animal Genomics, GIGA-R and Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
authors.forename: Carole
authors.initials: C
authors.lastname: Charlier
mesh_terms: D000818:Animals; D002417:Cattle / Q000145:classification / Q000235:genetics*; D002418:Cattle Diseases / Q000235:genetics*; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D016109:Epidermolysis Bullosa, Junctional / Q000235:genetics / Q000662:veterinary*; D004982:Ethanolaminephosphotransferase; D005838:Genotype; D007797:Laminin / Q000235:genetics*; D059467:Transcriptome
chemical_list: D007797:Laminin; C095567:laminin alpha 3; D004982:Ethanolaminephosphotransferase
keywords: Belgian Blue cattle breed; LAMA3; autozygosity mapping; herlitz-type junctional epidermolysis bullosa; laminin-332; whole-genome sequencing