A COL11A2 mutation in Labrador retrievers with mild disproportionate dwarfism.
We describe a mild form of disproportionate dwarfism in Labrador Retrievers, which is not associated with any obvious health problems such as secondary arthrosis. We designate this phenotype as skeletal dysplasia 2 (SD2). It is inherited as a monogenic autosomal recessive trait with incomplete penet...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23527306/pdf/?tool=EBI |
| _version_ | 1818403945112928256 |
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| author | Mirjam Frischknecht Helena Niehof-Oellers Vidhya Jagannathan Marta Owczarek-Lipska Cord Drögemüller Elisabeth Dietschi Gaudenz Dolf Bernd Tellhelm Johann Lang Katriina Tiira Hannes Lohi Tosso Leeb |
| author_facet | Mirjam Frischknecht Helena Niehof-Oellers Vidhya Jagannathan Marta Owczarek-Lipska Cord Drögemüller Elisabeth Dietschi Gaudenz Dolf Bernd Tellhelm Johann Lang Katriina Tiira Hannes Lohi Tosso Leeb |
| author_sort | Mirjam Frischknecht |
| collection | DOAJ |
| description | We describe a mild form of disproportionate dwarfism in Labrador Retrievers, which is not associated with any obvious health problems such as secondary arthrosis. We designate this phenotype as skeletal dysplasia 2 (SD2). It is inherited as a monogenic autosomal recessive trait with incomplete penetrance primarily in working lines of the Labrador Retriever breed. Using 23 cases and 37 controls we mapped the causative mutation by genome-wide association and homozygosity mapping to a 4.44 Mb interval on chromosome 12. We re-sequenced the genome of one affected dog at 30x coverage and detected 92 non-synonymous variants in the critical interval. Only two of these variants, located in the lymphotoxin A (LTA) and collagen alpha-2(XI) chain gene (COL11A2), respectively, were perfectly associated with the trait. Previously described COL11A2 variants in humans or mice lead to skeletal dysplasias and/or deafness. The dog variant associated with disproportionate dwarfism, COL11A2:c.143G>C or p.R48P, probably has only a minor effect on collagen XI function, which might explain the comparatively mild phenotype seen in our study. The identification of this candidate causative mutation thus widens the known phenotypic spectrum of COL11A2 mutations. We speculate that non-pathogenic COL11A2 variants might even contribute to the heritable variation in height. |
| first_indexed | 2024-12-14T08:32:19Z |
| format | Article |
| id | doaj.art-124797f3f0c14cd2a7279e8e5ad860b0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T08:32:19Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-124797f3f0c14cd2a7279e8e5ad860b02022-12-21T23:09:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e6014910.1371/journal.pone.0060149A COL11A2 mutation in Labrador retrievers with mild disproportionate dwarfism.Mirjam FrischknechtHelena Niehof-OellersVidhya JagannathanMarta Owczarek-LipskaCord DrögemüllerElisabeth DietschiGaudenz DolfBernd TellhelmJohann LangKatriina TiiraHannes LohiTosso LeebWe describe a mild form of disproportionate dwarfism in Labrador Retrievers, which is not associated with any obvious health problems such as secondary arthrosis. We designate this phenotype as skeletal dysplasia 2 (SD2). It is inherited as a monogenic autosomal recessive trait with incomplete penetrance primarily in working lines of the Labrador Retriever breed. Using 23 cases and 37 controls we mapped the causative mutation by genome-wide association and homozygosity mapping to a 4.44 Mb interval on chromosome 12. We re-sequenced the genome of one affected dog at 30x coverage and detected 92 non-synonymous variants in the critical interval. Only two of these variants, located in the lymphotoxin A (LTA) and collagen alpha-2(XI) chain gene (COL11A2), respectively, were perfectly associated with the trait. Previously described COL11A2 variants in humans or mice lead to skeletal dysplasias and/or deafness. The dog variant associated with disproportionate dwarfism, COL11A2:c.143G>C or p.R48P, probably has only a minor effect on collagen XI function, which might explain the comparatively mild phenotype seen in our study. The identification of this candidate causative mutation thus widens the known phenotypic spectrum of COL11A2 mutations. We speculate that non-pathogenic COL11A2 variants might even contribute to the heritable variation in height.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23527306/pdf/?tool=EBI |
| spellingShingle | Mirjam Frischknecht Helena Niehof-Oellers Vidhya Jagannathan Marta Owczarek-Lipska Cord Drögemüller Elisabeth Dietschi Gaudenz Dolf Bernd Tellhelm Johann Lang Katriina Tiira Hannes Lohi Tosso Leeb A COL11A2 mutation in Labrador retrievers with mild disproportionate dwarfism. PLoS ONE |
| title | A COL11A2 mutation in Labrador retrievers with mild disproportionate dwarfism. |
| title_full | A COL11A2 mutation in Labrador retrievers with mild disproportionate dwarfism. |
| title_fullStr | A COL11A2 mutation in Labrador retrievers with mild disproportionate dwarfism. |
| title_full_unstemmed | A COL11A2 mutation in Labrador retrievers with mild disproportionate dwarfism. |
| title_short | A COL11A2 mutation in Labrador retrievers with mild disproportionate dwarfism. |
| title_sort | col11a2 mutation in labrador retrievers with mild disproportionate dwarfism |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23527306/pdf/?tool=EBI |
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