A Missense Variant in the Bardet-Biedl Syndrome 2 Gene (<i>BBS2</i>) Leads to a Novel Syndromic Retinal Degeneration in the Shetland Sheepdog
Canine progressive retinal atrophy (PRA) describes a group of hereditary diseases characterized 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 breed...
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MDPI AG
2021
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oai:doaj.org-article:3d0629e2e15e4956b71a3bea3c05e7c22021-11-25T17:41:46ZA Missense Variant in the Bardet-Biedl Syndrome 2 Gene (<i>BBS2</i>) Leads to a Novel Syndromic Retinal Degeneration in the Shetland Sheepdog10.3390/genes121117712073-4425https://doaj.org/article/3d0629e2e15e4956b71a3bea3c05e7c22021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1771https://doaj.org/toc/2073-4425Canine progressive retinal atrophy (PRA) describes a group of hereditary diseases characterized 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 (<i>BBS2</i>) (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.Rebekkah J. Hitti-MalinLouise M. BurmeisterFrode LingaasMaria KaukonenInka PettinenHannes LohiDavid SarganCathryn S. MellershMDPI AGarticlecaninePRAretinal degenerationBBS<i>BBS2</i>syndromicGeneticsQH426-470ENGenes, Vol 12, Iss 1771, p 1771 (2021) |
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canine PRA retinal degeneration BBS <i>BBS2</i> syndromic Genetics QH426-470 |
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canine PRA retinal degeneration BBS <i>BBS2</i> syndromic Genetics QH426-470 Rebekkah J. Hitti-Malin Louise M. Burmeister Frode Lingaas Maria Kaukonen Inka Pettinen Hannes Lohi David Sargan Cathryn S. Mellersh A Missense Variant in the Bardet-Biedl Syndrome 2 Gene (<i>BBS2</i>) Leads to a Novel Syndromic Retinal Degeneration in the Shetland Sheepdog |
| description |
Canine progressive retinal atrophy (PRA) describes a group of hereditary diseases characterized 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 (<i>BBS2</i>) (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. |
| format |
article |
| author |
Rebekkah J. Hitti-Malin Louise M. Burmeister Frode Lingaas Maria Kaukonen Inka Pettinen Hannes Lohi David Sargan Cathryn S. Mellersh |
| author_facet |
Rebekkah J. Hitti-Malin Louise M. Burmeister Frode Lingaas Maria Kaukonen Inka Pettinen Hannes Lohi David Sargan Cathryn S. Mellersh |
| author_sort |
Rebekkah J. Hitti-Malin |
| title |
A Missense Variant in the Bardet-Biedl Syndrome 2 Gene (<i>BBS2</i>) Leads to a Novel Syndromic Retinal Degeneration in the Shetland Sheepdog |
| title_short |
A Missense Variant in the Bardet-Biedl Syndrome 2 Gene (<i>BBS2</i>) Leads to a Novel Syndromic Retinal Degeneration in the Shetland Sheepdog |
| title_full |
A Missense Variant in the Bardet-Biedl Syndrome 2 Gene (<i>BBS2</i>) Leads to a Novel Syndromic Retinal Degeneration in the Shetland Sheepdog |
| title_fullStr |
A Missense Variant in the Bardet-Biedl Syndrome 2 Gene (<i>BBS2</i>) Leads to a Novel Syndromic Retinal Degeneration in the Shetland Sheepdog |
| title_full_unstemmed |
A Missense Variant in the Bardet-Biedl Syndrome 2 Gene (<i>BBS2</i>) Leads to a Novel Syndromic Retinal Degeneration in the Shetland Sheepdog |
| title_sort |
missense variant in the bardet-biedl syndrome 2 gene (<i>bbs2</i>) leads to a novel syndromic retinal degeneration in the shetland sheepdog |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/3d0629e2e15e4956b71a3bea3c05e7c2 |
| work_keys_str_mv |
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