A Nonsense Variant in the ST14 Gene 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 for ST14:c.388G>T, a nonsense variant that truncates >80% of the open reading frame of the ST14 gene (p.Glu130*). The variant leads to partial nonsense-mediated decay of the mutant transcript. Genetic variants in the ST14 gene are responsible for autosomal recessive congenital ichthyosis 11 in humans. Thus, the identified equine ST14: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.
Copyright © 2017 Bauer et al.
Publication Date: 2017-04-03 PubMed ID: 28235824PubMed Central: PMC5386879DOI: 10.1534/g3.117.039511Google Scholar: Lookup
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- Journal Article
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Summary
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This research studies Naked Foal Syndrome (NFS), a genetic skin condition in the Akhal-Teke horse breed, identifying a gene variant in the ST14 gene as the probable cause. This breakthrough will enable genetic testing to prevent unintentional breeding of NFS-affected foals.
Understanding NFS and ST14 Gene
- Naked Foal Syndrome (NFS) is a genetic skin disorder observed in Akhal-Teke horses, characterized by hairlessness and a mild form of ichthyosis (scaly skin). Horses affected by this syndrome usually die within 3 years, although the exact cause of these premature deaths remains unclear.
- The research demonstrates that NFS is a monogenic autosomal recessive trait – meaning the disease trait lies within only one gene and becomes discernible when inherited from both parents.
- The research identifies a nonsense variant in the ST14 gene, known to be associated with a comparable skin disorder in humans, as being strongly associated with NFS. This variant truncates more than 80% of the open reading frame of the ST14 gene, causing a partial breakdown of the mutant transcript.
Genetic Mapping and Whole Genome Sequencing
- The study first “mapped” the disease-causing gene to two different segments on chromosomes 7 and 27 in the horse genome, essentially narrowing down the location of the gene responsible for the disorder.
- Researchers then performed whole genome sequencing on two affected horses, two carriers of the disease, and 75 control horses from other breeds. Their analysis revealed a single nonsynonymous genetic variant (a variant that changes the protein sequence) on chromosome 7 that was strongly associated with NFS.
Findings and Implications
- The findings indicate that the genetic variant c.388G>T in the gene ST14 is a prime candidate for being the causative variant for NFS. Its identification will enable genetic testing in horses, thereby preventing unwanted NFS-affected foals through informed breeding.
- Fascinatingly, variants in the ST14 gene are responsible for a particular form of congenital ichthyosis (a similar skin disorder) in humans. This suggests that NFS-affected horses could potentially serve as a large animal model for studying this human skin disorder.
Cite This Article
APA
Bauer A, Hiemesch T, Jagannathan V, Neuditschko M, Bachmann I, Rieder S, Mikko S, Penedo MC, Tarasova N, Vitková M, Sirtori N, Roccabianca P, Leeb T, Welle MM.
(2017).
A Nonsense Variant in the ST14 Gene in Akhal-Teke Horses with Naked Foal Syndrome.
G3 (Bethesda), 7(4), 1315-1321.
https://doi.org/10.1534/g3.117.039511 Publication
Researcher Affiliations
- 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.
- Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001, Switzerland.
- Institute of Animal Breeding and Genetics, University of Göttingen, 37075, Germany.
- 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.
- 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.
- 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.
- 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.
- Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, 75007 Uppsala, Sweden.
- Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, California 95616.
- Russian Akhal-Teke Association, 115470 Moscow, Russia.
- International Akhal-Teke Association, 115470 Moscow, Russia.
- Equine Veterinary Practice, 91601 Stará Turá, Slovakia.
- Equine Veterinary Practice, 29010 Agazzano, Italy.
- Department of Veterinary Medicine, University of Milan, 20133, Italy.
- 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.
- DermFocus, University of Bern, 3001, Switzerland.
- Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3001, Switzerland.
MeSH Terms
- Animals
- Base Sequence
- Chromosome Mapping
- Codon, Nonsense / genetics
- Female
- Genetic Linkage
- Genetic Predisposition to Disease
- Heterozygote
- Horse Diseases / genetics
- Horse Diseases / pathology
- Horses / genetics
- Male
- Phenotype
- RNA, Messenger / genetics
- RNA, Messenger / metabolism
- Sequence Analysis, DNA
- Syndrome
- Tumor Suppressor Proteins / genetics
- Tumor Suppressor Proteins / metabolism
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