A COL7A1 mutation causes dystrophic epidermolysis bullosa in Rotes Höhenvieh cattle.

We identified a congenital mechanobullous skin disorder in six calves on a single farm of an endangered German cattle breed in 2010. The condition presented as a large loss of skin distal to the fetlocks and at the mucosa of the muzzle. All affected calves were euthanized on humane grounds due to th...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Annie Menoud, Monika Welle, Jens Tetens, Peter Lichtner, Cord Drögemüller
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c6e2d4dd86ff4e4f806d54f5d09d29be
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c6e2d4dd86ff4e4f806d54f5d09d29be
record_format	dspace
spelling	oai:doaj.org-article:c6e2d4dd86ff4e4f806d54f5d09d29be2021-11-18T07:15:54ZA COL7A1 mutation causes dystrophic epidermolysis bullosa in Rotes Höhenvieh cattle.1932-620310.1371/journal.pone.0038823https://doaj.org/article/c6e2d4dd86ff4e4f806d54f5d09d29be2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22715415/?tool=EBIhttps://doaj.org/toc/1932-6203We identified a congenital mechanobullous skin disorder in six calves on a single farm of an endangered German cattle breed in 2010. The condition presented as a large loss of skin distal to the fetlocks and at the mucosa of the muzzle. All affected calves were euthanized on humane grounds due to the severity, extent and progression of the skin and oral lesions. Examination of skin samples under light microscopy revealed detachment of the epidermis from the dermis at the level of the dermo epidermal junction, leading to the diagnosis of a subepidermal bullous dermatosis such as epidermolysis bullosa. The pedigree was consistent with monogenic autosomal recessive inheritance. We localized the causative mutation to an 18 Mb interval on chromosome 22 by homozygosity mapping. The COL7A1 gene encoding collagen type VII alpha 1 is located within this interval and COL7A1 mutations have been shown to cause inherited dystrophic epidermolysis bullosa (DEB) in humans. A SNP in the bovine COL7A1 exon 49 (c.4756C>T) was perfectly associated with the observed disease. The homozygous mutant T/T genotype was exclusively present in affected calves and their parents were heterozygous C/T confirming the assumed recessive mode of inheritance. All known cases and genotyped carriers were related to a single cow, which is supposed to be the founder animal. The mutant T allele was absent in 63 animals from 24 cattle breeds. The identified mutation causes a premature stop codon which leads to a truncated protein representing a complete loss of COL7A1 function (p.R1586*). We thus have identified a candidate causative mutation for this genetic disease using only three cases to unravel its molecular basis. Selection against this mutation can now be used to eliminate the mutant allele from the Rotes Höhenvieh breed.Annie MenoudMonika WelleJens TetensPeter LichtnerCord DrögemüllerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e38823 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Annie Menoud Monika Welle Jens Tetens Peter Lichtner Cord Drögemüller A COL7A1 mutation causes dystrophic epidermolysis bullosa in Rotes Höhenvieh cattle.
description	We identified a congenital mechanobullous skin disorder in six calves on a single farm of an endangered German cattle breed in 2010. The condition presented as a large loss of skin distal to the fetlocks and at the mucosa of the muzzle. All affected calves were euthanized on humane grounds due to the severity, extent and progression of the skin and oral lesions. Examination of skin samples under light microscopy revealed detachment of the epidermis from the dermis at the level of the dermo epidermal junction, leading to the diagnosis of a subepidermal bullous dermatosis such as epidermolysis bullosa. The pedigree was consistent with monogenic autosomal recessive inheritance. We localized the causative mutation to an 18 Mb interval on chromosome 22 by homozygosity mapping. The COL7A1 gene encoding collagen type VII alpha 1 is located within this interval and COL7A1 mutations have been shown to cause inherited dystrophic epidermolysis bullosa (DEB) in humans. A SNP in the bovine COL7A1 exon 49 (c.4756C>T) was perfectly associated with the observed disease. The homozygous mutant T/T genotype was exclusively present in affected calves and their parents were heterozygous C/T confirming the assumed recessive mode of inheritance. All known cases and genotyped carriers were related to a single cow, which is supposed to be the founder animal. The mutant T allele was absent in 63 animals from 24 cattle breeds. The identified mutation causes a premature stop codon which leads to a truncated protein representing a complete loss of COL7A1 function (p.R1586*). We thus have identified a candidate causative mutation for this genetic disease using only three cases to unravel its molecular basis. Selection against this mutation can now be used to eliminate the mutant allele from the Rotes Höhenvieh breed.
format	article
author	Annie Menoud Monika Welle Jens Tetens Peter Lichtner Cord Drögemüller
author_facet	Annie Menoud Monika Welle Jens Tetens Peter Lichtner Cord Drögemüller
author_sort	Annie Menoud
title	A COL7A1 mutation causes dystrophic epidermolysis bullosa in Rotes Höhenvieh cattle.
title_short	A COL7A1 mutation causes dystrophic epidermolysis bullosa in Rotes Höhenvieh cattle.
title_full	A COL7A1 mutation causes dystrophic epidermolysis bullosa in Rotes Höhenvieh cattle.
title_fullStr	A COL7A1 mutation causes dystrophic epidermolysis bullosa in Rotes Höhenvieh cattle.
title_full_unstemmed	A COL7A1 mutation causes dystrophic epidermolysis bullosa in Rotes Höhenvieh cattle.
title_sort	col7a1 mutation causes dystrophic epidermolysis bullosa in rotes höhenvieh cattle.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/c6e2d4dd86ff4e4f806d54f5d09d29be
work_keys_str_mv	AT anniemenoud acol7a1mutationcausesdystrophicepidermolysisbullosainroteshohenviehcattle AT monikawelle acol7a1mutationcausesdystrophicepidermolysisbullosainroteshohenviehcattle AT jenstetens acol7a1mutationcausesdystrophicepidermolysisbullosainroteshohenviehcattle AT peterlichtner acol7a1mutationcausesdystrophicepidermolysisbullosainroteshohenviehcattle AT corddrogemuller acol7a1mutationcausesdystrophicepidermolysisbullosainroteshohenviehcattle AT anniemenoud col7a1mutationcausesdystrophicepidermolysisbullosainroteshohenviehcattle AT monikawelle col7a1mutationcausesdystrophicepidermolysisbullosainroteshohenviehcattle AT jenstetens col7a1mutationcausesdystrophicepidermolysisbullosainroteshohenviehcattle AT peterlichtner col7a1mutationcausesdystrophicepidermolysisbullosainroteshohenviehcattle AT corddrogemuller col7a1mutationcausesdystrophicepidermolysisbullosainroteshohenviehcattle
_version_	1718423755502387200

A COL7A1 mutation causes dystrophic epidermolysis bullosa in Rotes Höhenvieh cattle.

Ejemplares similares