Whole Genome Sequencing of Giant Schnauzer Dogs with Progressive Retinal Atrophy Establishes NECAP1 as a Novel Candidate Gene for Retinal Degeneration

Genes

Maria Kaukonen¹  Hannes Lohi¹  David Sargan²  Tosso Leeb³  Anina Bauer³  RebekkahJ. Hitti⁴  EllenC. Schofield⁴  LouiseM. Burmeister⁴  JamesA. C. Oliver⁴  CathrynS. Mellersh⁴  OliverP. Forman⁵ 

[1] Department of Veterinary Biosciences, University of Helsinki, 00014 Helsinki, Finland;Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK;Institute of Genetics, University of Bern, 3001 Bern, Switzerland;Kennel Club Genetics Centre, Animal Health Trust, Lanwades Park, Newmarket, Suffolk CB8 7UU, UK;Wisdom Health, Waltham-on-the-Wolds, Leicestershire LE14 4RS, UK;

关键词: canine;    dog;    progressive retinal atrophy;    PRA;    retinal degeneration;   

DOI  :  10.3390/genes10050385

来源: DOAJ

【 摘 要 】

Canine progressive retinal atrophies (PRA) are genetically heterogeneous diseases characterized by retinal degeneration and subsequent blindness. PRAs are untreatable and affect multiple dog breeds, significantly impacting welfare. Three out of seven Giant Schnauzer (GS) littermates presented with PRA around four years of age. We sought to identify the causal variant to improve our understanding of the aetiology of this form of PRA and to enable development of a DNA test. Whole genome sequencing of two PRA-affected full-siblings and both unaffected parents was performed. Variants were filtered based on those segregating appropriately for an autosomal recessive disorder and predicted to be deleterious. Successive filtering against 568 canine genomes identified a single nucleotide variant in the gene encoding NECAP endocytosis associated 1 (NECAP1): c.544G>A (p.Gly182Arg). Five thousand one hundred and thirty canids of 175 breeds, 10 cross-breeds and 3 wolves were genotyped for c.544G>A. Only the three PRA-affected GS were homozygous (allele frequency in GS, excluding proband family = 0.015). In addition, we identified heterozygotes belonging to Spitz and Dachshund varieties, demonstrating c.544G>A segregates in other breeds of German origin. This study, in parallel with the known retinal expression and role of NECAP1 in clathrin mediated endocytosis (CME) in synapses, presents NECAP1 as a novel candidate gene for retinal degeneration in dogs and other species.

【 授权许可】

Unknown