An Intronic MBTPS2 Variant Results in a Splicing Defect in Horses with Brindle Coat Texture

Murgiano, Leonardo; Waluk, Dominik Pawel; Towers, Rachel; Wiedemar, Natalie; Dietrich, Sara Joëlle; Jagannathan, Vidhya; Drögemüller, Michaela; Balmer, Pierre; Druet, Tom; Galichet, Arnaud; Penedo, M Cecilia; Müller, Eliane Jasmine; Roosje, Petra; Welle, Monika Maria; Leeb, Tosso (2016). An Intronic MBTPS2 Variant Results in a Splicing Defect in Horses with Brindle Coat Texture. G3 Genes Genomes Genetics, 6(9), pp. 2963-2970. Genetics Society of America 10.1534/g3.116.032433

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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 semi-dominant mode of inheritance. Haplotype analyses identified a 5 Mb candidate region on chromosome X. Whole genome sequencing of 4 BR1 and 60 non-brindle 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 MBPTS2 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 MBPTS2 transcripts in skin and identified an aberrant transcript in a BR1 horse, which lacked the entire exon 10 and parts of exon 11. The MBPTS2:c1437+4T>C variant showed perfect co-segregation with the brindle phenotype in the investigated family and was absent from 457 control horses of diverse breeds. Altogether, our genetic data and the 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Pathologie > Forschungsgruppe Dermatologie
05 Veterinary Medicine > Research Foci > DermFocus
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV)
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV) > DKV - Dermatology
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

UniBE Contributor:

Murgiano, Leonardo; Waluk, Dominik Pawel; Wiedemar, Natalie; Dietrich, Sara Joëlle; Jagannathan, Vidya; Drögemüller, Michaela; Balmer, Pierre; Galichet, Arnaud; Müller, Eliane Jasmine; Roosje, Petra; Welle, Monika Maria and Leeb, Tosso

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology
500 Science > 590 Animals (Zoology)
600 Technology > 630 Agriculture

ISSN:

2160-1836

Publisher:

Genetics Society of America

Language:

English

Submitter:

Tosso Leeb

Date Deposited:

29 Aug 2016 08:24

Last Modified:

07 Feb 2017 11:04

Publisher DOI:

10.1534/g3.116.032433

PubMed ID:

27449517

Uncontrolled Keywords:

X-chromosome; dermatology; equus caballus; horse; whole genome sequencing

BORIS DOI:

10.7892/boris.85897

URI:

https://boris.unibe.ch/id/eprint/85897

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