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A Missense Mutation in the SERPINH1 Gene in Dachshunds with Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is a hereditary disease occurring in humans and dogs. It is characterized by extremely fragile bones and teeth. Most human and some canine OI cases are caused by mutations in the COL1A1 and COL1A2 genes encoding the subunits of collagen I. Recently, mutations in the CRTA...

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Autores principales: Drögemüller, Cord, Becker, Doreen, Brunner, Adrian, Haase, Bianca, Kircher, Patrick, Seeliger, Frank, Fehr, Michael, Baumann, Ulrich, Lindblad-Toh, Kerstin, Leeb, Tosso
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2708911/
https://www.ncbi.nlm.nih.gov/pubmed/19629171
http://dx.doi.org/10.1371/journal.pgen.1000579
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author Drögemüller, Cord
Becker, Doreen
Brunner, Adrian
Haase, Bianca
Kircher, Patrick
Seeliger, Frank
Fehr, Michael
Baumann, Ulrich
Lindblad-Toh, Kerstin
Leeb, Tosso
author_facet Drögemüller, Cord
Becker, Doreen
Brunner, Adrian
Haase, Bianca
Kircher, Patrick
Seeliger, Frank
Fehr, Michael
Baumann, Ulrich
Lindblad-Toh, Kerstin
Leeb, Tosso
author_sort Drögemüller, Cord
collection PubMed
description Osteogenesis imperfecta (OI) is a hereditary disease occurring in humans and dogs. It is characterized by extremely fragile bones and teeth. Most human and some canine OI cases are caused by mutations in the COL1A1 and COL1A2 genes encoding the subunits of collagen I. Recently, mutations in the CRTAP and LEPRE1 genes were found to cause some rare forms of human OI. Many OI cases exist where the causative mutation has not yet been found. We investigated Dachshunds with an autosomal recessive form of OI. Genotyping only five affected dogs on the 50 k canine SNP chip allowed us to localize the causative mutation to a 5.82 Mb interval on chromosome 21 by homozygosity mapping. Haplotype analysis of five additional carriers narrowed the interval further down to 4.74 Mb. The SERPINH1 gene is located within this interval and encodes an essential chaperone involved in the correct folding of the collagen triple helix. Therefore, we considered SERPINH1 a positional and functional candidate gene and performed mutation analysis in affected and control Dachshunds. A missense mutation (c.977C>T, p.L326P) located in an evolutionary conserved domain was perfectly associated with the OI phenotype. We thus have identified a candidate causative mutation for OI in Dachshunds and identified a fifth OI gene.
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spelling pubmed-27089112009-07-24 A Missense Mutation in the SERPINH1 Gene in Dachshunds with Osteogenesis Imperfecta Drögemüller, Cord Becker, Doreen Brunner, Adrian Haase, Bianca Kircher, Patrick Seeliger, Frank Fehr, Michael Baumann, Ulrich Lindblad-Toh, Kerstin Leeb, Tosso PLoS Genet Research Article Osteogenesis imperfecta (OI) is a hereditary disease occurring in humans and dogs. It is characterized by extremely fragile bones and teeth. Most human and some canine OI cases are caused by mutations in the COL1A1 and COL1A2 genes encoding the subunits of collagen I. Recently, mutations in the CRTAP and LEPRE1 genes were found to cause some rare forms of human OI. Many OI cases exist where the causative mutation has not yet been found. We investigated Dachshunds with an autosomal recessive form of OI. Genotyping only five affected dogs on the 50 k canine SNP chip allowed us to localize the causative mutation to a 5.82 Mb interval on chromosome 21 by homozygosity mapping. Haplotype analysis of five additional carriers narrowed the interval further down to 4.74 Mb. The SERPINH1 gene is located within this interval and encodes an essential chaperone involved in the correct folding of the collagen triple helix. Therefore, we considered SERPINH1 a positional and functional candidate gene and performed mutation analysis in affected and control Dachshunds. A missense mutation (c.977C>T, p.L326P) located in an evolutionary conserved domain was perfectly associated with the OI phenotype. We thus have identified a candidate causative mutation for OI in Dachshunds and identified a fifth OI gene. Public Library of Science 2009-07-24 /pmc/articles/PMC2708911/ /pubmed/19629171 http://dx.doi.org/10.1371/journal.pgen.1000579 Text en Drögemüller et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Drögemüller, Cord
Becker, Doreen
Brunner, Adrian
Haase, Bianca
Kircher, Patrick
Seeliger, Frank
Fehr, Michael
Baumann, Ulrich
Lindblad-Toh, Kerstin
Leeb, Tosso
A Missense Mutation in the SERPINH1 Gene in Dachshunds with Osteogenesis Imperfecta
title A Missense Mutation in the SERPINH1 Gene in Dachshunds with Osteogenesis Imperfecta
title_full A Missense Mutation in the SERPINH1 Gene in Dachshunds with Osteogenesis Imperfecta
title_fullStr A Missense Mutation in the SERPINH1 Gene in Dachshunds with Osteogenesis Imperfecta
title_full_unstemmed A Missense Mutation in the SERPINH1 Gene in Dachshunds with Osteogenesis Imperfecta
title_short A Missense Mutation in the SERPINH1 Gene in Dachshunds with Osteogenesis Imperfecta
title_sort missense mutation in the serpinh1 gene in dachshunds with osteogenesis imperfecta
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2708911/
https://www.ncbi.nlm.nih.gov/pubmed/19629171
http://dx.doi.org/10.1371/journal.pgen.1000579
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