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

Drögemüller, Cord; Becker, Doreen; Brunner, Adrian; Haase, Bianca; Kircher, Patrick Robert; Seeliger, Frank; Fehr, Michael; Baumann, Ulrich; Lindblad-Toh, Kerstin; Leeb, Tosso (2009). A Missense Mutation in the SERPINH1 Gene in Dachshunds with Osteogenesis Imperfecta. PLoS genetics, 5(7), e1000579. San Francisco, Calif.: Public Library of Science 10.1371/journal.pgen.1000579

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV) > DKV - Clinical Radiology
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV)
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
08 Faculty of Science > Departement of Chemistry and Biochemistry
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

UniBE Contributor:

Drögemüller, Cord; Becker, Doreen; Brunner, Adrian; Haase, Bianca; Kircher, Patrick Robert; Baumann, Ulrich and Leeb, Tosso

Subjects:

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

ISSN:

1553-7390

Publisher:

Public Library of Science

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:11

Last Modified:

16 Feb 2015 12:37

Publisher DOI:

10.1371/journal.pgen.1000579

PubMed ID:

19629171

Web of Science ID:

000269219500019

BORIS DOI:

10.7892/boris.31235

URI:

https://boris.unibe.ch/id/eprint/31235 (FactScience: 195658)

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