An intronic MBTPS2 variant results in a splicing defect in horses with brindle coat texture

• Published in: Journal of animal science Vol. 94; pp. 155 - 156
• Main Authors: Murgiano, L, Waluk, D, Towers, R, Wiedemar, N, Dietrich, J, Jagannathan, V, Drögemüller, M, Druet, T, Galichet, A, Penedo, M C, Müller, E, Roosje, P, Welle, M, Leeb, T
• Format: Journal Article
• Language: English
• Published: Champaign Oxford University Press 01.09.2016
• Subjects: Animal skins; Chromosomes; Deactivation; Exon skipping; Gene sequencing; Genomes; Genomics; Genotype & phenotype; Heredity; Horses; Ichthyosis; Inactivation; Keratosis; Missense mutation; Mutation; Pedigree; Peptidase; Phenotypes; Polymerase chain reaction; Ribonucleic acid; RNA; Skin; Splicing; Texture; X-chromosome inactivation
• ISSN: 0021-8812; 1525-3163

We investigated a family of horses exhibiting vertically striped patterns in their hair coat texture. This phenotype is termed "brindle" by horse breeders. Pedigree analyses were suggestive of a monogenic X-chromosomal dominant mode of inheritance. The striped pattern in affected female horses followed the lines of Blaschko thought to be a consequence of female X chromosome inactivation with subsequent expansion of cell clones expressing either the wild-type or mutant allele. Thus the striped pattern in the brindle phenotype supports the putative X-chromosomal dominant mode of inheritance. We analyzed whole genome sequences of 4 brindle and 62 non-brindle horses. The analysis revealed a private variant in intron 11 of the MBPTS2 gene encoding the membrane bound transcription factor peptidase, site 2. The variant was absent from 457 control horses of diverse breeds. Different missense mutations in the MBPTS2 gene lead to three related genodennatoses in human patients: ichthyosis follicularis, atrichia and photophobia (IFAR, OMIM #308205), Olmsted syndrome (OMIM #300918), and keratosis follicularis spinulosa decalvans (OMIM #308800). As the equine variant was very close to an exon/intron boundary (c.1437+4T > C), we analyzed MBPTS2 transcripts in skin RNA from an affected and a control horse. The control sample yielded only the expected RT-PCR band whereas in the affected animal we observed an additional aberrant transcript lacking the entire exon 10 and parts of exon 11. Our genetic data and the previous knowledge on MBTPS2 function suggest that the MBTPS2 intronic variant leads to partial exon skipping and causes the brindle phenotype in horses.