Canine chondrodysplasia caused by a truncating mutation in collagen-binding integrin alpha subunit 10.
The skeletal dysplasias are disorders of the bone and cartilage tissues. Similarly to humans, several dog breeds have been reported to suffer from different types of genetic skeletal disorders. We have studied the molecular genetic background of an autosomal recessive chondrodysplasia that affects t...
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ftdoajarticles:oai:doaj.org/article:1bfbde2f37a243c19fcc5e9ad56d2a37 2023-05-15T17:01:36+02:00 Canine chondrodysplasia caused by a truncating mutation in collagen-binding integrin alpha subunit 10. Kaisa Kyöstilä Anu K Lappalainen Hannes Lohi 2013-01-01T00:00:00Z https://doi.org/10.1371/journal.pone.0075621 https://doaj.org/article/1bfbde2f37a243c19fcc5e9ad56d2a37 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3783422?pdf=render https://doaj.org/toc/1932-6203 1932-6203 doi:10.1371/journal.pone.0075621 https://doaj.org/article/1bfbde2f37a243c19fcc5e9ad56d2a37 PLoS ONE, Vol 8, Iss 9, p e75621 (2013) Medicine R Science Q article 2013 ftdoajarticles https://doi.org/10.1371/journal.pone.0075621 2022-12-31T14:29:51Z The skeletal dysplasias are disorders of the bone and cartilage tissues. Similarly to humans, several dog breeds have been reported to suffer from different types of genetic skeletal disorders. We have studied the molecular genetic background of an autosomal recessive chondrodysplasia that affects the Norwegian Elkhound and Karelian Bear Dog breeds. The affected dogs suffer from disproportionate short stature dwarfism of varying severity. Through a genome-wide approach, we mapped the chondrodysplasia locus to a 2-Mb region on canine chromosome 17 in nine affected and nine healthy Elkhounds (praw = 7.42×10(-6), pgenome-wide = 0.013). The associated locus contained a promising candidate gene, cartilage specific integrin alpha 10 (ITGA10), and mutation screening of its 30 exons revealed a nonsense mutation in exon 16 (c.2083C>T; p.Arg695*) that segregated fully with the disease in both breeds (p = 2.5×10(-23)). A 24% mutation carrier frequency was indicated in NEs and an 8% frequency in KBDs. The ITGA10 gene product, integrin receptor α10-subunit combines into a collagen-binding α10β1 integrin receptor, which is expressed in cartilage chondrocytes and mediates chondrocyte-matrix interactions during endochondral ossification. As a consequence of the nonsense mutation, the α10-protein was not detected in the affected cartilage tissue. The canine phenotype highlights the importance of the α10β1 integrin in bone growth, and the large animal model could be utilized to further delineate its specific functions. Finally, this study revealed a candidate gene for human chondrodysplasias and enabled the development of a genetic test for breeding purposes to eradicate the disease from the two dog breeds. Article in Journal/Newspaper karelian Directory of Open Access Journals: DOAJ Articles Nes ENVELOPE(7.634,7.634,62.795,62.795) Nes’ ENVELOPE(44.681,44.681,66.600,66.600) PLoS ONE 8 9 e75621 |
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Medicine R Science Q |
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Medicine R Science Q Kaisa Kyöstilä Anu K Lappalainen Hannes Lohi Canine chondrodysplasia caused by a truncating mutation in collagen-binding integrin alpha subunit 10. |
topic_facet |
Medicine R Science Q |
description |
The skeletal dysplasias are disorders of the bone and cartilage tissues. Similarly to humans, several dog breeds have been reported to suffer from different types of genetic skeletal disorders. We have studied the molecular genetic background of an autosomal recessive chondrodysplasia that affects the Norwegian Elkhound and Karelian Bear Dog breeds. The affected dogs suffer from disproportionate short stature dwarfism of varying severity. Through a genome-wide approach, we mapped the chondrodysplasia locus to a 2-Mb region on canine chromosome 17 in nine affected and nine healthy Elkhounds (praw = 7.42×10(-6), pgenome-wide = 0.013). The associated locus contained a promising candidate gene, cartilage specific integrin alpha 10 (ITGA10), and mutation screening of its 30 exons revealed a nonsense mutation in exon 16 (c.2083C>T; p.Arg695*) that segregated fully with the disease in both breeds (p = 2.5×10(-23)). A 24% mutation carrier frequency was indicated in NEs and an 8% frequency in KBDs. The ITGA10 gene product, integrin receptor α10-subunit combines into a collagen-binding α10β1 integrin receptor, which is expressed in cartilage chondrocytes and mediates chondrocyte-matrix interactions during endochondral ossification. As a consequence of the nonsense mutation, the α10-protein was not detected in the affected cartilage tissue. The canine phenotype highlights the importance of the α10β1 integrin in bone growth, and the large animal model could be utilized to further delineate its specific functions. Finally, this study revealed a candidate gene for human chondrodysplasias and enabled the development of a genetic test for breeding purposes to eradicate the disease from the two dog breeds. |
format |
Article in Journal/Newspaper |
author |
Kaisa Kyöstilä Anu K Lappalainen Hannes Lohi |
author_facet |
Kaisa Kyöstilä Anu K Lappalainen Hannes Lohi |
author_sort |
Kaisa Kyöstilä |
title |
Canine chondrodysplasia caused by a truncating mutation in collagen-binding integrin alpha subunit 10. |
title_short |
Canine chondrodysplasia caused by a truncating mutation in collagen-binding integrin alpha subunit 10. |
title_full |
Canine chondrodysplasia caused by a truncating mutation in collagen-binding integrin alpha subunit 10. |
title_fullStr |
Canine chondrodysplasia caused by a truncating mutation in collagen-binding integrin alpha subunit 10. |
title_full_unstemmed |
Canine chondrodysplasia caused by a truncating mutation in collagen-binding integrin alpha subunit 10. |
title_sort |
canine chondrodysplasia caused by a truncating mutation in collagen-binding integrin alpha subunit 10. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doi.org/10.1371/journal.pone.0075621 https://doaj.org/article/1bfbde2f37a243c19fcc5e9ad56d2a37 |
long_lat |
ENVELOPE(7.634,7.634,62.795,62.795) ENVELOPE(44.681,44.681,66.600,66.600) |
geographic |
Nes Nes’ |
geographic_facet |
Nes Nes’ |
genre |
karelian |
genre_facet |
karelian |
op_source |
PLoS ONE, Vol 8, Iss 9, p e75621 (2013) |
op_relation |
http://europepmc.org/articles/PMC3783422?pdf=render https://doaj.org/toc/1932-6203 1932-6203 doi:10.1371/journal.pone.0075621 https://doaj.org/article/1bfbde2f37a243c19fcc5e9ad56d2a37 |
op_doi |
https://doi.org/10.1371/journal.pone.0075621 |
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PLoS ONE |
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8 |
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9 |
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e75621 |
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