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A frameshift insertion in SGK3 leads to recessive hairlessness in Scottish Deerhounds: a candidate gene for human alopecia conditions

Hairlessness is a breed-specific feature selected for in some dog breeds but a rare abnormality in some others such as Scottish Deerhounds (SD). In SDs, the affected puppies are born with sparse hair but lose it within the first 2 months leaving the dogs completely hairless. The previous studies hav...

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Autores principales: Hytönen, Marjo K., Lohi, Hannes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536473/
https://www.ncbi.nlm.nih.gov/pubmed/30927068
http://dx.doi.org/10.1007/s00439-019-02005-9
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author Hytönen, Marjo K.
Lohi, Hannes
author_facet Hytönen, Marjo K.
Lohi, Hannes
author_sort Hytönen, Marjo K.
collection PubMed
description Hairlessness is a breed-specific feature selected for in some dog breeds but a rare abnormality in some others such as Scottish Deerhounds (SD). In SDs, the affected puppies are born with sparse hair but lose it within the first 2 months leaving the dogs completely hairless. The previous studies have implicated variants in FOXI3 and SGK3 in hairlessness; however, the known variants do not explain hairlessness in all breeds such as SDs. We investigated the genetic cause in 66 SDs, including a litter with two hairless dogs. We utilized a combined approach of genome-wide homozygosity mapping and whole-genome sequencing of a hairless SD followed by recessive filtering according to a recessive model against 340 control genomes. Only two homozygous-coding variants were discovered in the homozygosity regions, including a 1-bp insertion in exon 2 of SGK3. This results in a predicted frameshift and very early truncation (49/490 amino acids) of the SGK3 protein. Additional screening of the recessive variant demonstrated a full segregation with the hairlessness and a 12% carrier frequency in the SD breed. The variant was not found in the related Irish Wolfhound breed. This study identifies the second hairless variant in the SGK3 gene in dogs and further highlights its role as a candidate gene for androgen-independent hair loss or alopecia in human. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00439-019-02005-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-65364732019-06-12 A frameshift insertion in SGK3 leads to recessive hairlessness in Scottish Deerhounds: a candidate gene for human alopecia conditions Hytönen, Marjo K. Lohi, Hannes Hum Genet Original Investigation Hairlessness is a breed-specific feature selected for in some dog breeds but a rare abnormality in some others such as Scottish Deerhounds (SD). In SDs, the affected puppies are born with sparse hair but lose it within the first 2 months leaving the dogs completely hairless. The previous studies have implicated variants in FOXI3 and SGK3 in hairlessness; however, the known variants do not explain hairlessness in all breeds such as SDs. We investigated the genetic cause in 66 SDs, including a litter with two hairless dogs. We utilized a combined approach of genome-wide homozygosity mapping and whole-genome sequencing of a hairless SD followed by recessive filtering according to a recessive model against 340 control genomes. Only two homozygous-coding variants were discovered in the homozygosity regions, including a 1-bp insertion in exon 2 of SGK3. This results in a predicted frameshift and very early truncation (49/490 amino acids) of the SGK3 protein. Additional screening of the recessive variant demonstrated a full segregation with the hairlessness and a 12% carrier frequency in the SD breed. The variant was not found in the related Irish Wolfhound breed. This study identifies the second hairless variant in the SGK3 gene in dogs and further highlights its role as a candidate gene for androgen-independent hair loss or alopecia in human. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00439-019-02005-9) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2019-03-29 2019 /pmc/articles/PMC6536473/ /pubmed/30927068 http://dx.doi.org/10.1007/s00439-019-02005-9 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Investigation
Hytönen, Marjo K.
Lohi, Hannes
A frameshift insertion in SGK3 leads to recessive hairlessness in Scottish Deerhounds: a candidate gene for human alopecia conditions
title A frameshift insertion in SGK3 leads to recessive hairlessness in Scottish Deerhounds: a candidate gene for human alopecia conditions
title_full A frameshift insertion in SGK3 leads to recessive hairlessness in Scottish Deerhounds: a candidate gene for human alopecia conditions
title_fullStr A frameshift insertion in SGK3 leads to recessive hairlessness in Scottish Deerhounds: a candidate gene for human alopecia conditions
title_full_unstemmed A frameshift insertion in SGK3 leads to recessive hairlessness in Scottish Deerhounds: a candidate gene for human alopecia conditions
title_short A frameshift insertion in SGK3 leads to recessive hairlessness in Scottish Deerhounds: a candidate gene for human alopecia conditions
title_sort frameshift insertion in sgk3 leads to recessive hairlessness in scottish deerhounds: a candidate gene for human alopecia conditions
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536473/
https://www.ncbi.nlm.nih.gov/pubmed/30927068
http://dx.doi.org/10.1007/s00439-019-02005-9
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