OMIA:001948-9940 : Epidermolysis bullosa, junctionalis, ITGB4-related in Ovis aries (sheep)
In other species: taurine cattle
Categories: Integument (skin) phene
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2015
Cross-species summary: Also known as Epidermolysis bullosa, junctional, non-Herlitz type
Mapping: By conducting a GWAS on 20 affected, 28 related normal and 48 unrelated normal Churra sheep, each of which had been genotyped with the Illumina OvineSNP50 BeadChip (yielding 44,785 informative SNPs), Suárez-Vega et al. (2015) mapped this disorder to chromosome OAR11, in the vicinity of marker rs410387229 at 54,939,690 bp (OARv3.1). Subsequent homozygosity mapping narrowed the region to "an 868-kb homozygous segment, from 54,632,309–55,500,100 bp". This implicated a very likely comparative locational candidate gene, namely ITGB4.
Molecular basis: Small deletion in Churra sheep: "a 4-bp deletion within exon 33 of the ITGB4 gene (c.4412_4415del;[ OAR11:54,849,767–54,849,770 bp; Oar v3.1]). The c.4412_4415del mutation causes a frameshift resulting in a premature stop codon at position 1472 of the integrin β4 protein" (Suárez-Vega et al., 2015)
Fabre et al. (2020) conducted whole genome sequencing of 2 unrelated affected French Mouton Vendeen lambs and 1 unaffected fullsib. Analysis of variants identified in 13 candidate genes “identified a novel SNP (OAR11_v4.0, g.54799925G>A) in exon 23 of the ITGB4 gene … whose variant allele causes a premature stop codon (p.Arg885*).” The variant segregated with the junctional epidermolysis bullosa phenotype in six affected lambs, 7 parents and 4 unaffected full-sib lambs (Fabre et al., 2020).
Prevalence: Genotyping for the g.54799925G>A variant in the French Mouton Vendeen meat sheep breed identified estimated allele frequencies of 6.3% in renewal ewe lambs, 5.2% for service rams and 6% in adult ewes (Fabre et al., 2020).
Mouton vendéen, France (Sheep) (VBO_0015497),
Spanish Churro (Sheep) (VBO_0001619).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|ITGB4||integrin beta 4||Ovis aries||11||NC_056064.1 (55215720..55183226)||ITGB4||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1272||Mouton vendéen, France (Sheep)||Epidermolysis bullosa, junctionalis, ITGB4||ITGB4||nonsense (stop-gain)||Naturally occurring variant||Oar_rambouillet_v1.0||11||g.7412626C>T||c.2653C>T||p.(R885*)||c.2653C>T position is based on mRNA XM_015098951.1; Oar_v4.0 position is g.54799925||2020||33225458|
|543||Spanish Churro (Sheep)||Epidermolysis bullosa, junctionalis, ITGB4||ITGB4||deletion, small (<=20)||Naturally occurring variant||Oar_rambouillet_v1.0||11||g.7425460_7425463del||c.4412_4415del||Oar_v3.1: g.54849767_54849770del||2015||25955497||The genomic location on Oar_rambouillet_v1.0 was determined by Katie Eager, EMAI, NSW Department of Primary Industries.|
Cite this entry
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2020||Fabre, S., Chantepie, L., Plisson-Petit, F., Sarry, J., Woloszyn, F., Genet, C., Drouilhet, L., Tosser-Klopp, G. :|
|A novel homozygous nonsense mutation in ITGB4 gene causes epidermolysis bullosa in Mouton Vendéen sheep. Anim Genet :, 2020. Pubmed reference: 33225458 . DOI: 10.1111/age.13026.|
|2015||Suárez-Vega, A., Gutiérrez-Gil, B., Benavides, J., Perez, V., Tosser-Klopp, G., Klopp, C., Keennel, S.J., Arranz, J.J. :|
|Combining GWAS and RNA-Seq approaches for detection of the causal mutation for hereditary junctional epidermolysis bullosa in sheep. PLoS One 10:e0126416, 2015. Pubmed reference: 25955497 . DOI: 10.1371/journal.pone.0126416.|
- Created by Frank Nicholas on 17 May 2015
- Changed by Frank Nicholas on 17 May 2015
- Changed by Imke Tammen2 on 30 Nov 2020