A KRT71 Loss-of-Function Variant Results in Inner Root Sheath Dysplasia and Recessive Congenital Hypotrichosis of Hereford Cattle

Jacinto, Joana G. P.; Markey, Alysta D.; Veiga, Inês M. B.; Paris, Julia M.; Welle, Monika; Beever, Jonathan E.; Drögemüller, Cord (2021). A KRT71 Loss-of-Function Variant Results in Inner Root Sheath Dysplasia and Recessive Congenital Hypotrichosis of Hereford Cattle. Genes, 12(7), p. 1038. MDPI, Molecular Diversity Preservation International 10.3390/genes12071038

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Genodermatoses, such as heritable skin disorders, mostly represent Mendelian conditions. Congenital hypotrichosis (HY) characterize a condition of being born with less hair than normal. The purpose of this study was to characterize the clinicopathological phenotype of a breed-specific non-syndromic form of HY in Hereford cattle and to identify the causative genetic variant for this recessive disorder. Affected calves showed a very short, fine, wooly, kinky and curly coat over all parts of the body, with a major expression in the ears, the inner part of the limbs, and in the thoracic-abdominal region. Histopathology showed a severely altered morphology of the inner root sheath (IRS) of the hair follicle with abnormal Huxley and Henle’s layers and severely dysplastic hair shafts. A genome-wide association study revealed an association signal on chromosome 5. Homozygosity mapping in a subset of cases refined the HY locus to a 690 kb critical interval encompassing a cluster of type II keratin encoding genes. Protein-coding exons of six positional candidate genes with known hair or hair follicle function were re-sequenced. This revealed a protein-changing variant in the KRT71 gene that encodes a type II keratin specifically expressed in the IRS of the hair follicle (c.281delTGTGCCCA; p.Met94AsnfsX14). Besides obvious phenocopies, a perfect concordance between the presence of this most likely pathogenic loss-of-function variant located in the head domain of KRT71 and the HY phenotype was found. This recessive KRT71-related form of hypotrichosis provides a novel large animal model for similar human conditions. The results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 002114-9913).

Item Type:

Journal Article (Original Article)

Division/Institute:

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

UniBE Contributor:

Pontes Jacinto, Joana Goncalves; Berenguer Veiga, Inês Margarida; Paris, Julia Maria; Welle, Monika Maria and Drögemüller, Cord

Subjects:

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

ISSN:

2073-4425

Publisher:

MDPI, Molecular Diversity Preservation International

Language:

English

Submitter:

Cord Drögemüller

Date Deposited:

06 Jul 2021 08:35

Last Modified:

11 Jul 2021 03:12

Publisher DOI:

10.3390/genes12071038

BORIS DOI:

10.48350/157332

URI:

https://boris.unibe.ch/id/eprint/157332

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