A Large Deletion in the NSDHL Gene in Labrador Retrievers with a Congenital Cornification Disorder
Autor: | Monika Maria Welle, Tosso Leeb, Margaret L. Casal, Anina Bauer, Giorgia Mezzalira, Vidhya Jagannathan, Michela De Lucia |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
skin Candidate gene 040301 veterinary sciences media_common.quotation_subject 610 Medicine & health QH426-470 Biology 0403 veterinary science 03 medical and health sciences Exon Genetics medicine Molecular Biology Genetics (clinical) X chromosome media_common X-chromosome Whole genome sequencing whole genome sequencing Daughter 630 Agriculture animal model canis lupus familiaris 04 agricultural and veterinary sciences CHILD syndrome medicine.disease Phenotype dermatology 030104 developmental biology dog 590 Animals (Zoology) 570 Life sciences biology Labrador Retriever lines of Blaschko |
Zdroj: | Bauer, Anina; De Lucia, Michela; Jagannathan, Vidhya; Mezzalira, Giorgia; Casal, Margaret L; Welle, Monika Maria; Leeb, Tosso (2017). A Large Deletion in the NSDHL Gene in Labrador Retrievers with a Congenital Cornification Disorder. G3 Genes Genomes Genetics, 7(9), pp. 3115-3121. Genetics Society of America 10.1534/g3.117.1124 G3: Genes, Genomes, Genetics, Vol 7, Iss 9, Pp 3115-3121 (2017) |
ISSN: | 2160-1836 |
Popis: | In heterozygous females affected by an X-linked skin disorder, lesions often appear in a characteristic pattern, the so-called Blaschko’s lines. We investigated a female Labrador Retriever and her crossbred daughter, which both showed similar clinical lesions that followed Blaschko’s lines. The two male littermates of the affected daughter had died at birth, suggesting a monogenic X-chromosomal semidominant mode of inheritance. Whole genome sequencing of the affected daughter, and subsequent automated variant filtering with respect to 188 nonaffected control dogs of different breeds, revealed 332 hetero-zygous variants on the X-chromosome private to the affected dog. None of these variants was protein-changing. By visual inspection of candidate genes located on the X-chromosome, we identified a large deletion in the NSDHL gene, encoding NAD(P) dependent steroid dehydrogenase-like, a 3β-hydroxysteroid dehydrogenase involved in cholesterol biosynthesis. The deletion spanned >14 kb, and included the last three exons of the NSDHL gene. By PCR and fragment length analysis, we confirmed the presence of the variant in both affected dogs, and its absence in 50 control Labrador Retrievers. Variants in the NSDHL gene cause CHILD syndrome in humans, and the bare patches (Bpa) and striated (Str) phenotypes in mice. Taken together, our genetic data and the known role of NSDHL in X-linked skin disorders strongly suggest that the identified structural variant in the NSDHL gene is causative for the phenotype in the two affected dogs. |
Databáze: | OpenAIRE |
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