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A stop‐gain in the laminin, alpha 3 gene causes recessive junctional epidermolysis bullosa in Belgian Blue cattle
Author(s) -
Sartelet Arnaud,
Harland Chad,
Tamma Nico,
Karim Latifa,
Bayrou Calixte,
Li Wanbo,
Ahariz Naima,
Coppieters Wouter,
Georges Michel,
Charlier Carole
Publication year - 2015
Publication title -
animal genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.756
H-Index - 81
eISSN - 1365-2052
pISSN - 0268-9146
DOI - 10.1111/age.12342
Subject(s) - biology , epidermolysis bullosa , junctional epidermolysis bullosa (veterinary medicine) , genetics , exon , gene , laminin , stop codon , microbiology and biotechnology , extracellular matrix
Summary 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 LAMA 3 gene that creates a premature stop codon (p.Arg2609*) in exon 60, truncating 22% of the corresponding protein. The LAMA 3 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.