A Large Deletion in the NSDHL Gene in Labrador Retrievers with a Congenital Cornification Disorder.

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

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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 semi-dominant mode of inheritance. Whole genome sequencing of the affected daughter and subsequent automated variant filtering with respect to 188 non-affected control dogs of different breeds revealed 332 heterozygous 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 more than 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > DermFocus
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Bauer, Anina; Jagannathan, Vidya; Welle, Monika Maria and Leeb, Tosso

Subjects:

500 Science > 590 Animals (Zoology)
600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2160-1836

Publisher:

Genetics Society of America

Language:

English

Submitter:

Tosso Leeb

Date Deposited:

07 Nov 2017 17:46

Last Modified:

08 Nov 2017 06:34

Publisher DOI:

10.1534/g3.117.1124

PubMed ID:

28739597

Uncontrolled Keywords:

X-chromosome animal model canis lupus familiaris dermatology dog lines of Blaschko skin whole genome sequencing

BORIS DOI:

10.7892/boris.104853

URI:

https://boris.unibe.ch/id/eprint/104853

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