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...
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ftmdpi:oai:mdpi.com:/2073-4425/11/6/636/ 2023-08-20T04:05:49+02:00 Novel Brown Coat Color (Cocoa) in French Bulldogs Results from a Nonsense Variant in HPS3 Sarah Kiener Alexandra Kehl Robert Loechel Ines Langbein-Detsch Elisabeth Müller Danika Bannasch Vidhya Jagannathan Tosso Leeb agris 2020-06-09 application/pdf https://doi.org/10.3390/genes11060636 EN eng Multidisciplinary Digital Publishing Institute Animal Genetics and Genomics https://dx.doi.org/10.3390/genes11060636 https://creativecommons.org/licenses/by/4.0/ Genes; Volume 11; Issue 6; Pages: 636 dog Canis lupus familiaris whole genome sequence wgs heterogeneity melanosome pigmentation Text 2020 ftmdpi https://doi.org/10.3390/genes11060636 2023-07-31T23:36:53Z 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 HPS3co. Text Canis lupus MDPI Open Access Publishing Genes 11 6 636 |
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MDPI Open Access Publishing |
op_collection_id |
ftmdpi |
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English |
topic |
dog Canis lupus familiaris whole genome sequence wgs heterogeneity melanosome pigmentation |
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dog Canis lupus familiaris whole genome sequence wgs heterogeneity melanosome pigmentation Sarah Kiener Alexandra Kehl Robert Loechel Ines Langbein-Detsch Elisabeth Müller Danika Bannasch Vidhya Jagannathan Tosso Leeb Novel Brown Coat Color (Cocoa) in French Bulldogs Results from a Nonsense Variant in HPS3 |
topic_facet |
dog Canis lupus familiaris whole genome sequence wgs heterogeneity melanosome pigmentation |
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 HPS3co. |
format |
Text |
author |
Sarah Kiener Alexandra Kehl Robert Loechel Ines Langbein-Detsch Elisabeth Müller Danika Bannasch Vidhya Jagannathan Tosso Leeb |
author_facet |
Sarah Kiener Alexandra Kehl Robert Loechel Ines Langbein-Detsch Elisabeth Müller Danika Bannasch Vidhya Jagannathan Tosso Leeb |
author_sort |
Sarah Kiener |
title |
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_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_sort |
novel brown coat color (cocoa) in french bulldogs results from a nonsense variant in hps3 |
publisher |
Multidisciplinary Digital Publishing Institute |
publishDate |
2020 |
url |
https://doi.org/10.3390/genes11060636 |
op_coverage |
agris |
genre |
Canis lupus |
genre_facet |
Canis lupus |
op_source |
Genes; Volume 11; Issue 6; Pages: 636 |
op_relation |
Animal Genetics and Genomics https://dx.doi.org/10.3390/genes11060636 |
op_rights |
https://creativecommons.org/licenses/by/4.0/ |
op_doi |
https://doi.org/10.3390/genes11060636 |
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Genes |
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11 |
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636 |
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