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...

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Autores principales: 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
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spelling oai:doaj.org-article:124797f3f0c14cd2a7279e8e5ad860b02021-11-18T07:52:32ZA COL11A2 mutation in Labrador retrievers with mild disproportionate dwarfism.1932-620310.1371/journal.pone.0060149https://doaj.org/article/124797f3f0c14cd2a7279e8e5ad860b02013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23527306/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203We 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.Mirjam FrischknechtHelena Niehof-OellersVidhya JagannathanMarta Owczarek-LipskaCord DrögemüllerElisabeth DietschiGaudenz DolfBernd TellhelmJohann LangKatriina TiiraHannes LohiTosso LeebPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e60149 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
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.
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.
format article
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
title A COL11A2 mutation in Labrador retrievers with mild disproportionate dwarfism.
title_short 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_sort col11a2 mutation in labrador retrievers with mild disproportionate dwarfism.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/124797f3f0c14cd2a7279e8e5ad860b0
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