title: A Nonsense Variant in theST14Gene in Akhal-Teke Horses with Naked Foal Syndrome.
abstract: Naked foal syndrome (NFS) is a genodermatosis in the Akhal-Teke horse breed. We provide the first scientific description of this phenotype. Affected horses have almost no hair and show a mild ichthyosis. So far, all known NFS affected horses died between a few weeks and 3 yr of age. It is not clear whether a specific pathology caused the premature deaths. NFS is inherited as a monogenic autosomal recessive trait. We mapped the disease causing genetic variant to two segments on chromosomes 7 and 27 in the equine genome. Whole genome sequencing of two affected horses, two obligate carriers, and 75 control horses from other breeds revealed a single nonsynonymous genetic variant on the chromosome 7 segment that was perfectly associated with NFS. The affected horses were homozygous forST14:c.388G>T, a nonsense variant that truncates >80% of the open reading frame of theST14gene (p.Glu130*). The variant leads to partial nonsense-mediated decay of the mutant transcript. Genetic variants in theST14gene are responsible for autosomal recessive congenital ichthyosis 11 in humans. Thus, the identified equineST14:c.388G>T variant is an excellent candidate causative variant for NFS, and the affected horses represent a large animal model for a known human genodermatosis. Our findings will enable genetic testing to avoid the nonintentional breeding of NFS-affected foals.
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001, Switzerland.|DermFocus, University of Bern, 3001, Switzerland.|Swiss Competence Center of Animal Breeding and Genetics, Bern University of Applied Sciences HAFL & Agroscope, University of Bern, 3001, Switzerland.
authors.forename: Anina
authors.identifier: 0000-0002-6765-4012
authors.initials: A
authors.lastname: Bauer
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001, Switzerland.|Institute of Animal Breeding and Genetics, University of Göttingen, 37075, Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Hiemesch
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001, Switzerland.|DermFocus, University of Bern, 3001, Switzerland.|Swiss Competence Center of Animal Breeding and Genetics, Bern University of Applied Sciences HAFL & Agroscope, University of Bern, 3001, Switzerland.
authors.forename: Vidhya
authors.initials: V
authors.lastname: Jagannathan
authors.affiliation: Swiss Competence Center of Animal Breeding and Genetics, Bern University of Applied Sciences HAFL & Agroscope, University of Bern, 3001, Switzerland.|Agroscope, Swiss National Stud Farm, 1580 Avenches, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Neuditschko
authors.affiliation: Swiss Competence Center of Animal Breeding and Genetics, Bern University of Applied Sciences HAFL & Agroscope, University of Bern, 3001, Switzerland.|Agroscope, Swiss National Stud Farm, 1580 Avenches, Switzerland.
authors.forename: Iris
authors.initials: I
authors.lastname: Bachmann
authors.affiliation: Swiss Competence Center of Animal Breeding and Genetics, Bern University of Applied Sciences HAFL & Agroscope, University of Bern, 3001, Switzerland.|Agroscope, Swiss National Stud Farm, 1580 Avenches, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rieder
authors.affiliation: Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, 75007 Uppsala, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Mikko
authors.affiliation: Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, California 95616.
authors.forename: M Cecilia
authors.initials: MC
authors.lastname: Penedo
authors.affiliation: Russian Akhal-Teke Association, 115470 Moscow, Russia.|International Akhal-Teke Association, 115470 Moscow, Russia.
authors.forename: Nadja
authors.initials: N
authors.lastname: Tarasova
authors.affiliation: Equine Veterinary Practice, 91601 Stará Turá, Slovakia.
authors.forename: Martina
authors.initials: M
authors.lastname: Vitková
authors.affiliation: Equine Veterinary Practice, 29010 Agazzano, Italy.
authors.forename: Nicolò
authors.initials: N
authors.lastname: Sirtori
authors.affiliation: Department of Veterinary Medicine, University of Milan, 20133, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Roccabianca
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001, Switzerland Tosso.Leeb@vetsuisse.unibe.ch.|DermFocus, University of Bern, 3001, Switzerland.|Swiss Competence Center of Animal Breeding and Genetics, Bern University of Applied Sciences HAFL & Agroscope, University of Bern, 3001, Switzerland.
authors.forename: Tosso
authors.identifier: 0000-0003-0553-4880
authors.initials: T
authors.lastname: Leeb
authors.affiliation: DermFocus, University of Bern, 3001, Switzerland.|Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3001, Switzerland.
authors.forename: Monika M
authors.initials: MM
authors.lastname: Welle
mesh_terms: D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D018389:Codon, Nonsense / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006734:Horse Diseases / Q000235:genetics* / Q000473:pathology; D006736:Horses / Q000235:genetics*; D008297:Male; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013577:Syndrome; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D018389:Codon, Nonsense; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins
keywords: Equus caballus; dermatology; genodermatosis; hair; skin; whole genome sequencing