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

Leonardo Murgiano, Dominik P. Waluk, Rachel Towers, Natalie Wiedemar, Joëlle Dietrich, Vidhya Jagannathan, Michaela Drögemüller, Pierre Balmer, Tom Druet, Arnaud Galichet, Cecilia Penedo, Eliane J. Müller, Petra Roosje, Monika M. Welle, Tosso Leeb

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

We investigated a family of horses exhibiting irregular vertical stripes in their hair coat texture along the neck, back, hindquarters, and upper legs. This phenotype is termed "brindle" by horse breeders. We propose the term "brindle 1 (BR1)" for this specific form of brindle. In some BR1 horses, the stripes were also differentially pigmented. Pedigree analyses were suggestive of a monogenic X-chromosomal semidominant mode of inheritance. Haplotype analyses identified a 5 Mb candidate region on chromosome X. Whole genome sequencing of four BR1 and 60 nonbrindle horses identified 61 private variants in the critical interval, none of them located in an exon of an annotated gene. However, one of the private variants was close to an exon/intron boundary in intron 10 of the MBTPS2 gene encoding the membrane bound transcription factor peptidase, site 2 (c.1437+4T>C). Different coding variants in this gene lead to three related genodermatoses in human patients. We therefore analyzed MBTPS2 transcripts in skin, and identified an aberrant transcript in a BR1 horse, which lacked the entire exon 10 and parts of exon 11. The MBTPS2:c1437+4T>Cvariant showed perfect cosegregation with the brindle phenotype in the investigated family, and was absent from 457 control horses of diverse breeds. Altogether, our genetic data, and previous knowledge on MBTPS2 function in the skin, suggest that the identified MBTPS2 intronic variant leads to partial exon skipping, and causes the BR1 phenotype in horses.

Original languageEnglish (US)
Pages (from-to)2963-2970
Number of pages8
JournalG3: Genes, Genomes, Genetics
Volume6
Issue number9
DOIs
StatePublished - Jan 1 2016

Fingerprint

Horses
Exons
Phenotype
Introns
Genes
Skin
X Chromosome
Pedigree
Hair
Haplotypes
Leg
Peptide Hydrolases
Transcription Factors
Neck
Genome
Membranes

Keywords

  • Dermatology
  • Equus Caballus
  • Hair
  • Lines of Blaschko
  • X-chromosome

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Murgiano, L., Waluk, D. P., Towers, R., Wiedemar, N., Dietrich, J., Jagannathan, V., ... Leeb, T. (2016). An intronic MBTPS2 variant results in a splicing defect in horses with brindle coat texture. G3: Genes, Genomes, Genetics, 6(9), 2963-2970. https://doi.org/10.1534/g3.116.032433

An intronic MBTPS2 variant results in a splicing defect in horses with brindle coat texture. / Murgiano, Leonardo; Waluk, Dominik P.; Towers, Rachel; Wiedemar, Natalie; Dietrich, Joëlle; Jagannathan, Vidhya; Drögemüller, Michaela; Balmer, Pierre; Druet, Tom; Galichet, Arnaud; Penedo, Cecilia; Müller, Eliane J.; Roosje, Petra; Welle, Monika M.; Leeb, Tosso.

In: G3: Genes, Genomes, Genetics, Vol. 6, No. 9, 01.01.2016, p. 2963-2970.

Research output: Contribution to journalArticle

Murgiano, L, Waluk, DP, Towers, R, Wiedemar, N, Dietrich, J, Jagannathan, V, Drögemüller, M, Balmer, P, Druet, T, Galichet, A, Penedo, C, Müller, EJ, Roosje, P, Welle, MM & Leeb, T 2016, 'An intronic MBTPS2 variant results in a splicing defect in horses with brindle coat texture', G3: Genes, Genomes, Genetics, vol. 6, no. 9, pp. 2963-2970. https://doi.org/10.1534/g3.116.032433
Murgiano L, Waluk DP, Towers R, Wiedemar N, Dietrich J, Jagannathan V et al. An intronic MBTPS2 variant results in a splicing defect in horses with brindle coat texture. G3: Genes, Genomes, Genetics. 2016 Jan 1;6(9):2963-2970. https://doi.org/10.1534/g3.116.032433
Murgiano, Leonardo ; Waluk, Dominik P. ; Towers, Rachel ; Wiedemar, Natalie ; Dietrich, Joëlle ; Jagannathan, Vidhya ; Drögemüller, Michaela ; Balmer, Pierre ; Druet, Tom ; Galichet, Arnaud ; Penedo, Cecilia ; Müller, Eliane J. ; Roosje, Petra ; Welle, Monika M. ; Leeb, Tosso. / An intronic MBTPS2 variant results in a splicing defect in horses with brindle coat texture. In: G3: Genes, Genomes, Genetics. 2016 ; Vol. 6, No. 9. pp. 2963-2970.
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