Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Deletion in the Bardet-Biedl Syndrome Gene TTC8 Results in a Syndromic Retinal Degeneration in Dogs

Suvi Mäkeläinen
ORCID logo ,
Minas Hellsand
ORCID logo ,
Anna Darlene van der Heiden
,
Elina Andersson
,
Elina Thorsson
,
Bodil Ström-Holst
ORCID logo ,
Jens Häggström
,
Ingrid Ljungvall
,
Cathryn Mellersh
,
Finn Hallbook
,
Göran Andersson
ORCID logo ,
Björn Ekesten
ORCID logo ,
Tomas F. Bergström
* ORCID logo
Version 1 : Received: 25 August 2020 / Approved: 26 August 2020 / Online: 26 August 2020 (12:24:47 CEST)

A peer-reviewed article of this Preprint also exists.

Mäkeläinen, S.; Hellsand, M.; van der Heiden, A.D.; Andersson, E.; Thorsson, E.; S. Holst, B.; Häggström, J.; Ljungvall, I.; Mellersh, C.; Hallböök, F.; Andersson, G.; Ekesten, B.; Bergström, T.F. Deletion in the Bardet–Biedl Syndrome Gene TTC8 Results in a Syndromic Retinal Degeneration in Dogs. Genes 2020, 11, 1090. Mäkeläinen, S.; Hellsand, M.; van der Heiden, A.D.; Andersson, E.; Thorsson, E.; S. Holst, B.; Häggström, J.; Ljungvall, I.; Mellersh, C.; Hallböök, F.; Andersson, G.; Ekesten, B.; Bergström, T.F. Deletion in the Bardet–Biedl Syndrome Gene TTC8 Results in a Syndromic Retinal Degeneration in Dogs. Genes 2020, 11, 1090.

Abstract

In golden retriever dogs, a 1 bp deletion in the canine TTC8 gene has been shown to cause progressive retinal atrophy (PRA), the canine equivalent of retinitis pigmentosa. In humans, TTC8 is also implicated in Bardet-Biedl syndrome (BBS). To investigate if the affected dogs only exhibit a non-syndromic PRA or develop a syndromic ciliopathy similar to human BBS, we recruited ten affected dogs to the study. The progression of PRA for two of the dogs was followed for two years, and a rigorous clinical characterization allowed a careful comparison with primary and secondary characteristics of human BBS. In addition to PRA, the dogs showed a spectrum of clinical and morphological signs similar to primary and secondary characteristics of human BBS patients, such as obesity, renal anomalies, sperm defects, and anosmia. We used Oxford Nanopore long-read cDNA sequencing to characterize retinal full-length TTC8 transcripts in affected and non-affected dogs, the results of which suggest that three isoforms are transcribed in the retina, and the 1 bp deletion is a loss-of-function mutation, resulting in a canine form of Bardet-Biedl syndrome with heterogeneous clinical signs.

Keywords

Bardet-Biedl syndrome (BBS); retinal degeneration; primary cilia; ciliopathy; dog; BBS8; TTC8; progressive retinal atrophy (PRA); retinitis pigmentosa

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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