title: A partial gene deletion of SLC45A2 causes oculocutaneous albinism in Doberman pinscher dogs.
abstract: The first white Doberman pinscher (WDP) dog was registered by the American Kennel Club in 1976. The novelty of the white coat color resulted in extensive line breeding of this dog and her offspring. The WDP phenotype closely resembles human oculocutaneous albinism (OCA) and clinicians noticed a seemingly high prevalence of pigmented masses on these dogs. This study had three specific aims: (1) produce a detailed description of the ocular phenotype of WDPs, (2) objectively determine if an increased prevalence of ocular and cutaneous melanocytic tumors was present in WDPs, and (3) determine if a genetic mutation in any of the genes known to cause human OCA is causal for the WDP phenotype. WDPs have a consistent ocular phenotype of photophobia, hypopigmented adnexal structures, blue irides with a tan periphery and hypopigmented retinal pigment epithelium and choroid. WDPs have a higher prevalence of cutaneous melanocytic neoplasms compared with control standard color Doberman pinschers (SDPs); cutaneous tumors were noted in 12/20 WDP (<5 years of age: 4/12; >5 years of age: 8/8) and 1/20 SDPs (p<0.00001). Using exclusion analysis, four OCA causative genes were investigated for their association with WDP phenotype; TYR, OCA2, TYRP1 and SLC45A2. SLC45A2 was found to be linked to the phenotype and gene sequencing revealed a 4,081 base pair deletion resulting in loss of the terminus of exon seven of SLC45A2 (chr4∶77,062,968-77,067,051). This mutation is highly likely to be the cause of the WDP phenotype and is supported by a lack of detectable SLC45A2 transcript levels by reverse transcriptase PCR. The WDP provides a valuable model for studying OCA4 visual disturbances and melanocytic neoplasms in a large animal model.
authors.affiliation: Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, United States of America; Genetics Program, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Paige A
authors.initials: PA
authors.lastname: Winkler
authors.affiliation: Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, United States of America.
authors.forename: Kara R
authors.initials: KR
authors.lastname: Gornik
authors.affiliation: The Animal Ophthalmology Center, Williamston, Michigan, United States of America.
authors.forename: David T
authors.initials: DT
authors.lastname: Ramsey
authors.affiliation: Comparative Ocular Pathology Laboratory of Wisconsin, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Dubielzig
authors.affiliation: Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, United States of America; Genetics Program, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Venta
authors.affiliation: Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, United States of America; Genetics Program, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Petersen-Jones
authors.affiliation: Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Bartoe
mesh_terms: D016115:Albinism, Oculocutaneous / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D000818:Animals; D001483:Base Sequence; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D004283:Dog Diseases / Q000235:genetics* / Q000473:pathology; D004285:Dogs; D004587:Electrophoresis, Agar Gel; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction
chemical_list: D018076:DNA, Complementary; D026901:Membrane Transport Proteins