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Open AccessArticle

Novel Brown Coat Color (Cocoa) in French Bulldogs Results from a Nonsense Variant in HPS3

1
Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland
2
Dermfocus, University of Bern, 3001 Bern, Switzerland
3
Laboklin, 97688 Bad Kissingen, Germany
4
VetGen, Ann Arbor, MI 48108, USA
5
Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
*
Author to whom correspondence should be addressed.
Genes 2020, 11(6), 636; https://doi.org/10.3390/genes11060636
Received: 15 May 2020 / Revised: 5 June 2020 / Accepted: 8 June 2020 / Published: 9 June 2020
(This article belongs to the Special Issue Coat Color Genetics)
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. View Full-Text
Keywords: dog; Canis lupus familiaris; whole genome sequence; wgs; heterogeneity; melanosome; pigmentation dog; Canis lupus familiaris; whole genome sequence; wgs; heterogeneity; melanosome; pigmentation
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Kiener, S.; Kehl, A.; Loechel, R.; Langbein-Detsch, I.; Müller, E.; Bannasch, D.; Jagannathan, V.; Leeb, T. Novel Brown Coat Color (Cocoa) in French Bulldogs Results from a Nonsense Variant in HPS3. Genes 2020, 11, 636.

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