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Canine inherited retinal degenerations: a model for visual impairment in humans

Mäkeläinen, Suvi (2020). Canine inherited retinal degenerations: a model for visual impairment in humans. Diss. (sammanfattning/summary) Sveriges lantbruksuniv., Acta Universitatis Agriculturae Sueciae, 1652-6880
ISBN 978-91-7760-626-0
eISBN 978-91-7760-627-7
[Doctoral thesis]

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Inherited retinal degenerations (IRDs) form a clinically and genetically heterogeneous group of diseases, leading to visual impairment or blindness in both humans and dogs. The prevalence of IRDs is estimated at 1 in 2,000 in humans. In dogs, the exact prevalence is unknown, but close to 100 different breeds have been reported to be affected, many by more than one type of IRD. The identification of the underlying genetic variants is critical, as the results can be used to develop genetic tests, which allow breeders to make informed breeding decisions while preserving genetic variation.

In Labrador retrievers, a novel form of IRD was recently identified, with clinical signs indicating cone-rod photoreceptor degeneration. In this thesis, a whole-genome sequencing approach was used to identify a frameshift insertion leading to a premature stop codon in the canine ABCA4 gene. In humans, mutations in the ABCA4 gene are the major cause of Stargardt disease (STGD), an autosomal recessive retinal degeneration leading to central visual impairment. Transcript and protein level investigations showed that the canine ABCA4 insertion is a loss-of-function mutation responsible for the novel canine IRD, and leads to a phenotype similar to STGD in humans.

Golden retrievers are affected by at least four different forms of IRD, one of which is associated with a deletion in the TTC8 gene. Mutations in this gene in humans are involved in the Bardet-Biedl syndrome (BBS) with heterogeneous clinical signs. We were able to show that the canine deletion is a loss-of-function mutation resulting in a syndromic IRD similar to BBS.

Lastly, while the human retinal transcriptome has been extensively studied, less is known about the gene expression patterns in the canine retina. Using short- and longread cDNA sequencing we characterized the canine retinal transcriptome, results that in the future can be used to identify and validate causative genetic variants for canine IRDs. The results of this thesis contribute to the understanding of two important IRDs affecting the health and welfare of both dogs and humans. In addition, the thesis highlights the importance of a well-characterized retinal transcriptome for successful identification of disease-causing alleles.

Authors/Creators:Mäkeläinen, Suvi
Title:Canine inherited retinal degenerations: a model for visual impairment in humans
Series Name/Journal:Acta Universitatis Agriculturae Sueciae
Year of publishing :2020
Number of Pages:71
Publisher:Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences
ISBN for printed version:978-91-7760-626-0
ISBN for electronic version:978-91-7760-627-7
Publication Type:Doctoral thesis
Article category:Other scientific
Version:Published version
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Medical Genetics
(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Genetics (medical genetics to be 30107 and agricultural genetics to be 40402)
(A) Swedish standard research categories 2011 > 1 Natural sciences > 102 Computer and Information Science > 10203 Bioinformatics (Computational Biology) (applications to be 10610)
Keywords:dog, retina, PRA, retinopathy, ABCA4, Stargardt disease, TTC8, Bardet-Biedl syndrome, whole-genome sequencing, transcriptome
Permanent URL:
ID Code:17778
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Animal Breeding and Genetics
Deposited By: SLUpub Connector
Deposited On:12 Oct 2020 08:00
Metadata Last Modified:15 Jan 2021 19:44

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