@article{30fd4837fbc4444da3b57a81da03e678,
title = "A missense variant in the Bardet-Biedl syndrome 2 gene (BBS2) leads to a novel syndromic retinal degeneration in the shetland sheepdog",
abstract = "Canine progressive retinal atrophy (PRA) describes a group of hereditary diseases char-acterized by photoreceptor cell death in the retina, leading to visual impairment. Despite the identification of multiple PRA-causing variants, extensive heterogeneity of PRA is observed across and within dog breeds, with many still genetically unsolved. This study sought to elucidate the causal variant for a distinct form of PRA in the Shetland sheepdog, using a whole-genome sequencing approach. Filtering variants from a single PRA-affected Shetland sheepdog genome compared to 176 genomes of other breeds identified a single nucleotide variant in exon 11 of the Bardet–Biedl syndrome-2 gene (BBS2) (c.1222G>C; p.Ala408Pro). Genotyping 1386 canids of 155 dog breeds, 15 cross breeds and 8 wolves indicated the c.1222G>C variant was only segregated within Shetland sheepdogs. Out of 505 Shetland sheepdogs, seven were homozygous for the variant. Clinical history and photographs for three homozygotes indicated the presence of a novel phenotype. In addition to PRA, additional clinical features in homozygous dogs support the discovery of a novel syndromic PRA in the breed. The development and utilization of a diagnostic DNA test aim to prevent the mutation from becoming more prevalent in the breed.",
keywords = "BBS, BBS2, Canine, PRA, Retinal degeneration, Syndromic",
author = "Hitti-Malin, {Rebekkah J.} and Burmeister, {Louise M.} and Frode Lingaas and Maria Kaukonen and Inka Pettinen and Hannes Lohi and David Sargan and Mellersh, {Cathryn S.}",
note = "Funding Information: Acknowledgments: The authors would like to thank all SS owners for submitting DNA samples and clinical information from their dogs. WGS of the proband was conducted through the AHT {\textquoteleft}Give a Dog a Genome{\textquoteright} sequencing project, funded equally by the Kennel Club Charitable Trust and the English Shetland Sheepdog Club UK. We thank the High-Throughput Genomics Group at the Wellcome Trust Center for Human Genetics (funded by Wellcome Trust grant reference 090532/Z/09/Z) to generate the WES, and Edinburgh Genomics laboratories, the University of Edinburgh for the generation of the WGS data. We thank Ellen Schofield and Mike Boursnell for WGS bioinformatics assistance and Sally Ricketts for initial sample collation and her expertise. The authors also thank Sue Pearce-Kelling for sharing knowledge of a canine TTC8 phenotype and Leonardo Murgiano at The University of Pennsylvania, USA, for providing DNA samples to genotype. We thank the other members of the Dog Biomedical Variant Database Consortium (DBVDC; Gus Aguirre, Catherine Andr{\'e}, Danika Bannasch, Doreen Becker, Brian Davis, Cord Dr{\"o}gem{\"u}ller, Kari Ekenstedt, Kiterie Faller, Oliver Forman, Steve Friedenberg, Eva Furrow, Urs Giger, Christophe Hitte, Marjo Hyt{\"o}nen, Vidhya Jagannathan, Tosso Leeb, Hannes Lohi, Jim Mickelson, Leonardo Murgiano, Anita Oberbauer, Sheila Schmutz, Jeffrey Schoenebeck, Kim Summers, Frank van Steen-beek, Claire Wade) and Natasha Olby (NCSU) for sharing WGS data from control dogs. At the time of the study, R.J.H-M, L.M.B and C.S.M were supported by the Kennel Club Charitable Trust in the Kennel Club Genetics Center at the AHT. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2021",
month = nov,
doi = "10.3390/genes12111771",
language = "English",
volume = "12",
journal = "Genes",
issn = "2073-4425",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "11",
}