Donskoy cats as a new model of oculocutaneous albinism with the identification of a splice‐site variant in Hermansky–Pudlak Syndrome 5 gene

• Published in: Pigment cell and melanoma research Vol. 33; no. 6; pp. 814 - 825
• Main Authors: Mériot, Marina, Hitte, Christophe, Rimbault, Maud, Dufaure de Citres, Caroline, Gache, Vincent, Abitbol, Marie
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.11.2020
• Subjects: Albinism; Amino acids; Autosomal recessive inheritance; BLOC2S2; Cancer; Cats; Felis catus; Gene mapping; Genome-wide association studies; Genomes; Genotyping; Heredity; Hermansky–Pudlak Syndrome 5; Homozygosity; Life Sciences; Mapping; Organelles; Phenotypes; ruby‐eye 2; Single-nucleotide polymorphism; Splicing; ruby-eye 2; Hermansky-Pudlak Syndrome 5; Felis catus; albinism; BLOC2S2
• ISSN: 1755-1471; 1755-148X
• DOI: 10.1111/pcmr.12906

In the feline Donskoy breed, a phenotype that breeders call "pink‐eye," with associated light‐brown skin, yellow irises and red‐eye effect, has been described. Genealogical data indicated an autosomal recessive inheritance pattern. A single candidate region was identified by genome‐wide association study and SNP‐based homozygosity mapping. Within that region, we further identified HPS5 (HPS5 Biogenesis Of Lysosomal Organelles Complex 2 Subunit 2) as a strong candidate gene, since HPS5 variants have been identified in humans and animals with Hermansky–Pudlak syndrome 5 or oculocutaneous albinism. A homozygous c.2571‐1G>A acceptor splice‐site variant located in intron 16 of HPS5 was identified in pink‐eye cats. Segregation of the variant was 100% consistent with the inheritance pattern. Genotyping of 170 cats from 19 breeds failed to identify a single carrier in non‐Donskoy cats. The c.2571‐1G>A variant leads to HPS5 exon‐16 splicing that is predicted to produce a 52 amino acids in‐frame deletion in the protein. These results support an association of the pink‐eye phenotype with the c.2571‐1G>A variant. The pink‐eye Donskoy cat extends the panel of reported HPS5 variants and offers an opportunity for in‐depth exploration of the phenotypic consequences of a new HPS5 variant.