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Novel Brown Coat Color (Cocoa) in French Bulldogs Results from a Nonsense Variant in HPS3
Brown or chocolate coat color in many mammalian species is frequently due to variants at the B locus or TYRP1 gene. In dogs, five different TYRP1 loss-of-function alleles have been described, which explain the vast majority of dogs with brown coat color. Recently, breeders and genetic testing labora...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349258/ https://www.ncbi.nlm.nih.gov/pubmed/32526956 http://dx.doi.org/10.3390/genes11060636 |
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author | Kiener, Sarah Kehl, Alexandra Loechel, Robert Langbein-Detsch, Ines Müller, Elisabeth Bannasch, Danika Jagannathan, Vidhya Leeb, Tosso |
author_facet | Kiener, Sarah Kehl, Alexandra Loechel, Robert Langbein-Detsch, Ines Müller, Elisabeth Bannasch, Danika Jagannathan, Vidhya Leeb, Tosso |
author_sort | Kiener, Sarah |
collection | PubMed |
description | Brown or chocolate coat color in many mammalian species is frequently due to variants at the B locus or TYRP1 gene. In dogs, five different TYRP1 loss-of-function alleles have been described, which explain the vast majority of dogs with brown coat color. Recently, breeders and genetic testing laboratories identified brown French Bulldogs that did not carry any of the known mutant TYRP1 alleles. We sequenced the genome of a TYRP1(+/+) brown French Bulldog and compared the data to 655 other canine genomes. A search for private variants revealed a nonsense variant in HPS3, c.2420G>A or p.(Trp807*). The brown dog was homozygous for the mutant allele at this variant. The HPS3 gene encodes a protein required for the correct biogenesis of lysosome-related organelles, including melanosomes. Variants in the human HPS3 gene cause Hermansky–Pudlak syndrome 3, which involves a mild form of oculocutaneous albinism and prolonged bleeding time. A variant in the murine Hps3 gene causes brown coat color in the cocoa mouse mutant. We genotyped a cohort of 373 French Bulldogs and found a strong association of the homozygous mutant HPS3 genotype with the brown coat color. The genotype–phenotype association and the comprehensive knowledge on HPS3 function from other species strongly suggests that HPS3:c.2420G>A is the causative variant for the observed brown coat color in French Bulldogs. In order to clearly distinguish HPS3-related from the TYRP1-related brown coat color, and in line with the murine nomenclature, we propose to designate this dog phenotype as “cocoa”, and the mutant allele as HPS3(co). |
format | Online Article Text |
id | pubmed-7349258 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73492582020-07-22 Novel Brown Coat Color (Cocoa) in French Bulldogs Results from a Nonsense Variant in HPS3 Kiener, Sarah Kehl, Alexandra Loechel, Robert Langbein-Detsch, Ines Müller, Elisabeth Bannasch, Danika Jagannathan, Vidhya Leeb, Tosso Genes (Basel) Article Brown or chocolate coat color in many mammalian species is frequently due to variants at the B locus or TYRP1 gene. In dogs, five different TYRP1 loss-of-function alleles have been described, which explain the vast majority of dogs with brown coat color. Recently, breeders and genetic testing laboratories identified brown French Bulldogs that did not carry any of the known mutant TYRP1 alleles. We sequenced the genome of a TYRP1(+/+) brown French Bulldog and compared the data to 655 other canine genomes. A search for private variants revealed a nonsense variant in HPS3, c.2420G>A or p.(Trp807*). The brown dog was homozygous for the mutant allele at this variant. The HPS3 gene encodes a protein required for the correct biogenesis of lysosome-related organelles, including melanosomes. Variants in the human HPS3 gene cause Hermansky–Pudlak syndrome 3, which involves a mild form of oculocutaneous albinism and prolonged bleeding time. A variant in the murine Hps3 gene causes brown coat color in the cocoa mouse mutant. We genotyped a cohort of 373 French Bulldogs and found a strong association of the homozygous mutant HPS3 genotype with the brown coat color. The genotype–phenotype association and the comprehensive knowledge on HPS3 function from other species strongly suggests that HPS3:c.2420G>A is the causative variant for the observed brown coat color in French Bulldogs. In order to clearly distinguish HPS3-related from the TYRP1-related brown coat color, and in line with the murine nomenclature, we propose to designate this dog phenotype as “cocoa”, and the mutant allele as HPS3(co). MDPI 2020-06-09 /pmc/articles/PMC7349258/ /pubmed/32526956 http://dx.doi.org/10.3390/genes11060636 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kiener, Sarah Kehl, Alexandra Loechel, Robert Langbein-Detsch, Ines Müller, Elisabeth Bannasch, Danika Jagannathan, Vidhya Leeb, Tosso Novel Brown Coat Color (Cocoa) in French Bulldogs Results from a Nonsense Variant in HPS3 |
title | Novel Brown Coat Color (Cocoa) in French Bulldogs Results from a Nonsense Variant in HPS3 |
title_full | Novel Brown Coat Color (Cocoa) in French Bulldogs Results from a Nonsense Variant in HPS3 |
title_fullStr | Novel Brown Coat Color (Cocoa) in French Bulldogs Results from a Nonsense Variant in HPS3 |
title_full_unstemmed | Novel Brown Coat Color (Cocoa) in French Bulldogs Results from a Nonsense Variant in HPS3 |
title_short | Novel Brown Coat Color (Cocoa) in French Bulldogs Results from a Nonsense Variant in HPS3 |
title_sort | novel brown coat color (cocoa) in french bulldogs results from a nonsense variant in hps3 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349258/ https://www.ncbi.nlm.nih.gov/pubmed/32526956 http://dx.doi.org/10.3390/genes11060636 |
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