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: Arnaud Sartelet, Chad Harland, Nico Tamma, Latifa Karim, Calixte Bayrou, Wanbo Li, Naima Ahariz, Wouter Coppieters, Michel Georges, Carole Charlier
• Journal: Animal genetics (Anim Genet) Vol. 46 Issue 5 Pg. 566-70 (Oct 2015) ISSN: 1365-2052 [Electronic] England
• PMID: 26370913 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Stichting International Foundation for Animal Genetics.

Chemical References

• Laminin
• laminin alpha 3
• Ethanolaminephosphotransferase

Topics

• Animals
• Cattle (classification, genetics)
• Cattle Diseases (genetics)
• Chromosome Mapping
• DNA Mutational Analysis
• Epidermolysis Bullosa, Junctional (genetics, veterinary)
• Ethanolaminephosphotransferase
• Genotype
• Laminin (genetics)
• Transcriptome