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Donskoy cats as a new model of oculocutaneous albinism with the identification of a splice‐site variant in Hermansky – Pudlak Syndrome 5 gene
Author(s) -
Mériot Marina,
Hitte Christophe,
Rimbault Maud,
Dufaure de Citres Caroline,
Gache Vincent,
Abitbol Marie
Publication year - 2020
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12906
Subject(s) - hermansky–pudlak syndrome , oculocutaneous albinism , genetics , biology , albinism , exon , splice site mutation , phenotype , candidate gene , splice , gene , alternative splicing , medicine , pathology , pulmonary fibrosis , fibrosis
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.