Abstract
Ichthyoses are a group of various different types of hereditary disorders affecting skin cornification. They are characterized by hyperkeratoses of different severity levels and are associated with a dry and scaling skin. Genome-wide association analysis of nine affected and 13 unaffected Great Danes revealed a genome-wide significant peak on chromosome 9 at 57–58 Mb in the region of SLC27A4. Sequence analysis of genomic DNA of SLC27A4 revealed the non-synonymous SNV SLC27A4:g.8684G>A in perfect association with ichthyosis-affection in Great Danes. The mutant transcript of SLC27A4 showed an in-frame loss of 54 base pairs in exon 8 probably induced by a new splice acceptor site motif created by the mutated A- allele of the SNV. Genotyping 413 controls from 35 different breeds of dogs and seven wolves revealed that this mutation could not be found in other populations except in Great Danes. Affected dogs revealed high amounts of mutant transcript but only low levels of the wild type transcript. Targeted analyses of SLC27A4 protein from skin tissues of three affected and two unaffected Great Danes indicated a markedly reduced or not detectable wild type and truncated protein levels in affected dogs but a high expression of wild type SLC27A4 protein in unaffected controls. Our data provide evidence of a new splice acceptor site creating SNV that results in a reduction or loss of intact SLC27A4 protein and probably explains the severe skin phenotype in Great Danes. Genetic testing will allow selective breeding to prevent ichthyosis-affected puppies in the future.
Highlights
Hereditary ichthyoses represent a heterogenous group of skin cornification disorders that affect the entire integument and are characterized by hyperkeratosis and blistering or scaling [1, 2]
We examined 15 cases of Great Dane puppies affected with ichthyosiform dermatosis from five different litters
Dominant and X-linked modes of inheritance can be excluded because parents were normal and both sexes were affected
Summary
Hereditary ichthyoses represent a heterogenous group of skin cornification disorders that affect the entire integument and are characterized by hyperkeratosis and blistering or scaling [1, 2]. A wide variety of mutations have been shown to be responsible for different types of ichthyoses [3, 4]. They were classified into syndromic and non-syndromic forms and further subgroups with regard to clinical signs, onset of the disease and genetic background. On the whole 36 genes have been detected which were supposed to be involved in non-syndromic. SLC27A4 Associated with Congenital Ichthyosis and/or syndromic human ichthyoses [1]. For the investigation of the causative mutations for human ichthyoses domestic animals have been shown to be useful model organisms. Ichthyosiform dermatoses have been described in cattle, mice, rats, dogs and pigs [5,6,7,8,9,10,11,12,13,14,15]
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