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, Vidya; Leeb, Tosso (2020). Novel Brown Coat Color (Cocoa) in French Bulldogs Results from a Nonsense Variant in HPS3. Genes, 11(6) MDPI, Molecular Diversity Preservation International 10.3390/genes11060636

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > DermFocus
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

UniBE Contributor:

Kiener, Sarah; Bannasch, Danika; Jagannathan, Vidya and Leeb, Tosso

Subjects:

500 Science > 590 Animals (Zoology)
600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2073-4425

Publisher:

MDPI, Molecular Diversity Preservation International

Language:

English

Submitter:

Tosso Leeb

Date Deposited:

16 Jun 2020 14:52

Last Modified:

16 Jun 2020 14:52

Publisher DOI:

10.3390/genes11060636

PubMed ID:

32526956

Uncontrolled Keywords:

Canis lupus familiaris dog heterogeneity melanosome pigmentation wgs whole genome sequence

BORIS DOI:

10.7892/boris.144677

URI:

https://boris.unibe.ch/id/eprint/144677

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