{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:09:58Z","timestamp":1760234998922,"version":"build-2065373602"},"reference-count":19,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T00:00:00Z","timestamp":1626652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>A nonsense variant in HPS3, c.2420G&gt;A or p.Trp807*, was recently discovered as the cause for a brown coat color termed cocoa in French Bulldogs. Here, we studied the genotype\u2013phenotype correlation regarding coat color in HPS3 mutant dogs that carried various combinations of mutant alleles at other coat color genes. Different combinations of HPS3, MLPH and TYRP1 genotypes resulted in subtly different shades of brown coat colors. As HPS3 variants in humans cause the Hermansky\u2013Pudlak syndrome type 3, which in addition to oculocutaneous albinism is characterized by a storage pool deficiency leading to bleeding tendency, we also investigated the phenotypic consequences of the HPS3 variant in French Bulldogs on hematological parameters. HPS3 mutant dogs had a significantly lowered platelet dense granules abundance. However, no increased bleeding tendencies in daily routine were reported by dog owners. We therefore conclude that in dogs, the phenotypic effect of the HPS3 variant is largely restricted to pigmentation. While an effect on platelet morphology is evident, we did not obtain any indications for major health problems associated with the cocoa coat color in French Bulldogs. Further studies will be necessary to definitely rule out very subtle effects on visual acuity or a clinically relevant bleeding disorder.<\/jats:p>","DOI":"10.3390\/genes12071092","type":"journal-article","created":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T10:07:37Z","timestamp":1626689257000},"page":"1092","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of Cocoa Genotypes on Coat Color, Platelets and Coagulation Parameters in French Bulldogs"],"prefix":"10.3390","volume":"12","author":[{"given":"Anna","family":"Laukner","sequence":"first","affiliation":[{"name":"Laboklin GmbH&Co.KG, Steubenstra\u00dfe 4, 97688 Bad Kissingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Truchet","sequence":"additional","affiliation":[{"name":"Laboklin GmbH&Co.KG, Steubenstra\u00dfe 4, 97688 Bad Kissingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgi","family":"Manukjan","sequence":"additional","affiliation":[{"name":"Institute of Experimental Biomedicine, University Hospital Wuerzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1285-6407","authenticated-orcid":false,"given":"Harald","family":"Schulze","sequence":"additional","affiliation":[{"name":"Institute of Experimental Biomedicine, University Hospital Wuerzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ines","family":"Langbein-Detsch","sequence":"additional","affiliation":[{"name":"Laboklin GmbH&Co.KG, Steubenstra\u00dfe 4, 97688 Bad Kissingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Mueller","sequence":"additional","affiliation":[{"name":"Laboklin GmbH&Co.KG, Steubenstra\u00dfe 4, 97688 Bad Kissingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0553-4880","authenticated-orcid":false,"given":"Tosso","family":"Leeb","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1547-0713","authenticated-orcid":false,"given":"Alexandra","family":"Kehl","sequence":"additional","affiliation":[{"name":"Laboklin GmbH&Co.KG, Steubenstra\u00dfe 4, 97688 Bad Kissingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1007\/s00335-001-2147-2","article-title":"TYRP1 and MC1R genotypes and their effects on coat color in dogs","volume":"13","author":"Schmutz","year":"2002","journal-title":"Mamm. Genome"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1111\/age.12563","article-title":"A novel mutation in the TYRP1 gene associated with brown coat colour in the Australian Shepherd Dog Breed","volume":"48","author":"Turnova","year":"2017","journal-title":"Anim. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/age.13037","article-title":"A novel TYRP1 mutation associated with brown coat color in Siberian huskies","volume":"52","author":"Mickelson","year":"2021","journal-title":"Anim. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1111\/age.12839","article-title":"A novel TYRP1 variant is associated with liver and tan coat colour in Lancashire Heelers","volume":"50","author":"Wright","year":"2019","journal-title":"Anim. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kiener, S., Kehl, A., Loechel, R., Langbein-Detsch, I., M\u00fcller, E., Bannasch, D., Jagannathan, V., and Leeb, T. (2020). Novel Brown Coat Color (Cocoa) in French Bulldogs Results from a Nonsense Variant in HPS. Genes, 11.","DOI":"10.3390\/genes11060636"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"301","DOI":"10.5482\/HAMO-14-06-0024","article-title":"Hermansky-Pudlak syndrome. Overview of clinical and molecular features and case report of a new HPS-1 variant","volume":"34","author":"Torregrosa","year":"2014","journal-title":"Hamostaseologie"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.ccm.2016.04.012","article-title":"Hermansky-Pudlak Syndrome","volume":"37","author":"Young","year":"2016","journal-title":"Clin. 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Blood Cancer"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/7\/1092\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:31:46Z","timestamp":1760164306000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/7\/1092"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,19]]},"references-count":19,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["genes12071092"],"URL":"https:\/\/doi.org\/10.3390\/genes12071092","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2021,7,19]]}}}