in Sheep

In this study, we demonstrate the use of a genome-wide association mapping together with RNA-seq in a reduced number of samples, as an efficient approach to detect the causal mu-tation for a Mendelian disease. Junctional epidermolysis bullosa is a recessive genoderma-tosis that manifests with neonatal mechanical fragility of the skin, blistering confined to the lamina lucida of the basement membrane and severe alteration of the hemidesmosomal junctions. In Spanish Churra sheep, junctional epidermolysis bullosa (JEB) has been de-tected in two commercial flocks. The JEB locus was mapped toOvis aries chromosome 11 by GWAS and subsequently fine-mapped to an 868-kb homozygous segment using the identical-by-descent method. The ITGB4, which is located within this region, was identified as the best positional and functional candidate gene. The RNA-seq variant analysis enabled us to discover a 4-bp deletion within exon 33 of the ITGB4 gene (c.4412_4415del). The c.4412_4415delmutation causes a frameshift resulting in a premature stop codon at posi-tion 1472 of the integrin β4 protein. A functional analysis of this deletion revealed decrease