A mutation in the FAM83G gene in dogs with hereditary footpad hyperkeratosis (HFH)

Drögemüller, Michaela; Jagannathan, Vidhya; Becker, Doreen; Drögemüller, Cord; Schelling, Claude; Plassais, Jocelyn; Kaerle, Cécile; Dufaure de Citres, Caroline; Thomas, Anne; Müller, Eliane Jasmine; Welle, Monika Maria; Roosje, Petra; Leeb, Tosso (2014). A mutation in the FAM83G gene in dogs with hereditary footpad hyperkeratosis (HFH). PLoS genetics, 10(5), e1004370. Public Library of Science 10.1371/journal.pgen.1004370

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Hereditary footpad hyperkeratosis (HFH) represents a palmoplantar hyperkeratosis, which is inherited as a monogenic autosomal recessive trait in several dog breeds, such as e.g. Kromfohrländer and Irish Terriers. We performed genome-wide association studies (GWAS) in both breeds. In Kromfohrländer we obtained a single strong association signal on chromosome 5 (p(raw) = 1.0×10(-13)) using 13 HFH cases and 29 controls. The association signal replicated in an independent cohort of Irish Terriers with 10 cases and 21 controls (p(raw) = 6.9×10(-10)). The analysis of shared haplotypes among the combined Kromfohrländer and Irish Terrier cases defined a critical interval of 611 kb with 13 predicted genes. We re-sequenced the genome of one affected Kromfohrländer at 23.5× coverage. The comparison of the sequence data with 46 genomes of non-affected dogs from other breeds revealed a single private non-synonymous variant in the critical interval with respect to the reference genome assembly. The variant is a missense variant (c.155G>C) in the FAM83G gene encoding a protein with largely unknown function. It is predicted to change an evolutionary conserved arginine into a proline residue (p.R52P). We genotyped this variant in a larger cohort of dogs and found perfect association with the HFH phenotype. We further studied the clinical and histopathological alterations in the epidermis in vivo. Affected dogs show a moderate to severe orthokeratotic hyperplasia of the palmoplantar epidermis. Thus, our data provide the first evidence that FAM83G has an essential role for maintaining the integrity of the palmoplantar epidermis.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > DermFocus
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV)
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 Clinical Veterinary Medicine (DKV) > DKV - Dermatology
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

UniBE Contributor:

Drögemüller, Michaela; Jagannathan, Vidya; Becker, Doreen; Drögemüller, Cord; Müller, Eliane Jasmine; Welle, Monika Maria; Roosje, Petra and Leeb, Tosso

Subjects:

500 Science > 590 Animals (Zoology)
600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture

ISSN:

1553-7390

Publisher:

Public Library of Science

Language:

English

Submitter:

Tosso Leeb

Date Deposited:

29 Jan 2015 14:29

Last Modified:

28 Nov 2020 02:25

Publisher DOI:

10.1371/journal.pgen.1004370

PubMed ID:

24832243

BORIS DOI:

10.7892/boris.62420

URI:

https://boris.unibe.ch/id/eprint/62420

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