In other species: sheep

Categories: Integument (skin) phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 147557 (gene) , 226650 (trait)

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: Searching for regions of extended homozygosity in the affacted calf enabled Peters et al. (2015) to map this disorder to "a 54.7 Mb interval from 7.6 to 62.3 Mb" on chromosome BTA19. This region contains four comparative candidate genes, including ITGB4 (see below).

Molecular basis: By whole-genome sequencing a single affected Charolais calf, and concentrating on comparative functional candidate genes based on careful diagnosis, Peters et al. (2015) identified the causative mutation to be "a 4.4 kb deletion involving exons 17 to 22" of the ITGB4 gene. The authors noted that "The transcript of the mutant allele lacked information regarding a significant part of the encoded protein since the deletion led to a frameshift and a premature stop codon. It was therefore assumed that the mutant transcripts probably underwent nonsense mediated decay so that, in the final analysis, the deletion represented a loss-of-function mutation with a non-existing integrin protein in the epidermis of the affected animal." Genotyping of 162 Charolais from the same herd confirmed the association between this deletion and the disorder.

Michot et al. (2015) independently mapped the disorder in Charolais and identified the same causal mutation.

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Breed: Charolais (Cattle) (VBO_0000177).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene: