LAMA3; laminin-332; Herlitz-type Junctional Epidermolysis Bullosa; autozygosity mapping; whole-genome sequencing; Belgian blue cattle breed
Abstract :
[en] 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.
Research center :
Giga-Genetics - ULiège
Disciplines :
Veterinary medicine & animal health Genetics & genetic processes
Author, co-author :
Sartelet, Arnaud ✱; Université de Liège > Département clinique des animaux de production (DCP) > Département clinique des animaux de production (DCP)
Harland, Chad ✱; Université de Liège > Département de productions animales > GIGA-R : Génomique animale
Tamma, Nico ; Université de Liège > Département de productions animales > GIGA-R : Génomique animale
Karim, Latifa ; Université de Liège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Bayrou, Calixte ; Université de Liège > Département de morphologie et pathologie > Pathologie spéciale et autopsies
Li, Wanbo; Université de Liège - ULiège > Département des productions animales > GIGA-R : Génomique animale
Ahariz, Naïma ; Université de Liège > Département de productions animales > GIGA-R : Génomique animale
Coppieters, Wouter ; Université de Liège > Département de productions animales > GIGA-R : Génomique animale
Georges, Michel ; Université de Liège > Département de productions animales > GIGA-R : Génomique animale
Charlier, Carole ; Université de Liège > Département de productions animales > GIGA-R : Génomique animale
✱ These authors have contributed equally to this work.
Language :
English
Title :
A stop-gain in the laminin, alpha 3 gene causes recessive junctional epidermolysis bullosa in Belgian Blue cattle
Publication date :
October 2015
Journal title :
Animal Genetics
ISSN :
0268-9146
eISSN :
1365-2052
Publisher :
Blackwell Publishing, Oxford, United Kingdom
Volume :
46
Issue :
5
Pages :
566-570
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Rilouke
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE] BELSPO - SPP Politique scientifique - Service Public Fédéral de Programmation Politique scientifique
Charlier C., Coppieters W., Rollin F., et al., (2008) Highly effective SNP-based association mapping and management of recessive defects in livestock. Nature Genetics 40, 449-54.
Fasquelle C., Sartelet A., Li W., et al., (2009) Balancing selection of a frame-shift mutation in the MRC2 gene accounts for the outbreak of the crooked tail syndrome in Belgian Blue cattle. PLoS Genetics 5, e1000666.
Has C., &, Bruckner-Tuderman L., (2014) The genetics of skin fragility. Annual Review of Genomics and Human Genetics 15, 245-68.
Li H., &, Durbin R., (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754-60.
McLaren W., Pritchard B., Rios D., Chen Y., Flicek P., &, Cunningham F., (2011) Deriving the consequences of genomic variants with the Ensembl API and snp effect predictor. Bioinformatics 26, 2069-70.
Medeiros G.X., Riet-Correa F., Armién A.G., Dantas A.F., de Galiza G.J., &, Simões S.V., (2012) Junctional epidermolysis bullosa in a calf. Journal of Veterinary Diagnostic Investigation 24, 231-4.
Medeiros G.X., &, Riet-Correa F., (2015) Epidermolysis bullosa in animals: a review. Veterinary Dermatology 26, 3-13.
Michot P., Fantini O., Braque R., et al., (2015) Whole-genome sequencing identifies a homozygous deletion encompassing exons 17 to 23 of the integrin beta 4 gene in a Charolais calf with junctional epidermolysis bullosa. Genetic Selection and Evolution 47, 37.
Murgiano L., Wiedemar N., Jagannathan V., Isling L.K., Drögemüller C., &, Agerholm J.S., (2015) Epidermolysis bullosa in Danish Hereford calves is caused by a deletion in LAMC2 gene. BMC Veterinary Research 11, 23.
Peters M., Reber I., Jagannathan V., Raddatz B., Wohlsein P., &, Drögemüller C., (2015) DNA-based diagnosis of rare diseases in veterinary medicine: a 4.4 kb deletion of ITGB4 is associated with epidermolysis bullosa in Charolais cattle. BMC Veterinary Research 11, 48.
Rimmer A., Phan H., Mathieson I., Iqbal Z., Twigg S.R., WGS500 Consortium, Wilkie A.O., McVean G., &, Lunter G., (2014) Integrating mapping-, assembly- and haplotype-based approaches for calling variants in clinical sequencing applications. Nature Genetics 46, 912-8.
Sartelet A., Druet T., Michaux C., Fasquelle C., Géron S., Tamma N., Zhang Z., Coppieters W., Georges M., &, Charlier C., (2012a) A splice site variant in the bovine RNF11 gene compromises growth and regulation of the inflammatory response. PLoS Genetics 8, e1002581.
Sartelet A., Klingbeil P., Franklin C.K., Fasquelle C., Géron S., Isacke C.M., Georges M., &, Charlier C., (2012b) Allelic heterogeneity of crooked tail syndrome: result of balancing selection? Animal Genetics 43, 604-7.
Sartelet A., Stauber T., Coppieters W., et al., (2014) A missense mutation accelerating the gating of the lysosomal Cl-/H+ -exchanger ClC-7/Ostm1 causes osteopetrosis with gingival hamartomas in cattle. Disease Models & Mechanisms 7, 119-28.
Sartelet A., Li W., Pailhoux E., et al., (2015) Genome-wide next-generation DNA and RNA sequencing reveals a mutation that perturbs splicing of the phosphatidylinositol glycan anchor biosynthesis class H gene (PIGH) and causes arthrogryposis in Belgian Blue cattle. BMC Genomics 16, 316.
Trapnell C., Roberts A., Goff L., Pertea G., Kim D., Kelley D.R., Pimentel H., Salzberg S.L., Rinn J.L., &, Pachter L., (2012) Differential gene and transcript expression analysis of RNA-seq experiments with tophat and cufflinks. Nature Protocols 7, 562-78.