G3: Genes, Genomes, Genetics (Apr 2017)

A Nonsense Variant in the ST14 Gene in Akhal-Teke Horses with Naked Foal Syndrome

  • Anina Bauer,
  • Theresa Hiemesch,
  • Vidhya Jagannathan,
  • Markus Neuditschko,
  • Iris Bachmann,
  • Stefan Rieder,
  • Sofia Mikko,
  • M. Cecilia Penedo,
  • Nadja Tarasova,
  • Martina Vitková,
  • Nicolò Sirtori,
  • Paola Roccabianca,
  • Tosso Leeb,
  • Monika M. Welle

DOI
https://doi.org/10.1534/g3.117.039511
Journal volume & issue
Vol. 7, no. 4
pp. 1315 – 1321

Abstract

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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.

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