Hypotrichosis, streaked

Phene ID

920

Name

Hypotrichosis, streaked

Phene Name

Streaked hairlessness

OMIA ID

542

Species ID

9913

Characterised

Yes

Characterised Year

2015

Eldridge and Atkeson (1953) reported extensive Holstein-Friesian data strongly suggestive of "a semi-dominant, sex-linked lethal". Murgiano et al. (2015) confirmed an X-linked semi-dominant mode of inheritance in Pezzata Rossa cattle.

Murgiano et al. (2015) investigated a family of Pezzata Rossa cattle with 4 affected cows. The pedigree was suggestive of X-linked semi-dominant inheritance with lethality in hemizygous mutant males. Two autosomal segments on chromosome 7 and 14 also showed positive LOD scores in a linkage analysis and could not definitively be excluded. Whole genome sequencing of one affected cow at 28x coverage and comparison to the 1000 bull genomes' sequence data identified two private coding variants in the critical intervals on BTA 7, 14, and X. These variants were a missense variant in ERCC6L and a splice site variant in TSR2. Expression analysis in mouse embryos demonstrated specific expression of TSR2 in developing hair-follicles whereas ERCC6L was not found to be expressed in hair follicles. Therefore, the authors concluded that the TSR2 variant (c.441+226A>G), which changed the conserved 3'-splice site of intron 4 from AG into GG, is the most likely causative variant. The authors analyzed the TSR2 transcripts in biopsies from lesional (hairless) and non-lesional skin areas from affected cows. The splice site variant leads to aberrant splicing with either retention of intron 4 or to a lesser degree activiation of a cryptic splice site within exon 5. The proportion of mutant transcripts was much higher in hairless skin compared to hairless skin, which is most likely due to a higher percentage of active X-chromosomes with the mutant allele. The transcript analysis thus provided very strong support for the causality of the TSR2 variant.