FYCO1 Frameshift Deletion in Wirehaired Pointing Griffon Dogs with Juvenile Cataract

Rudd Garces, Gabriela; Christen, Matthias; Loechel, Robert; Jagannathan, Vidhya; Leeb, Tosso (2022). FYCO1 Frameshift Deletion in Wirehaired Pointing Griffon Dogs with Juvenile Cataract. Genes, 13(2), p. 334. MDPI, Molecular Diversity Preservation International 10.3390/genes13020334

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Different breed-specific inherited cataracts have been described in dogs. In this study, we investigated an inbred family of Wirehaired Pointing Griffon dogs in which three offspring were affected by juvenile cataract. The pedigree suggested monogenic autosomal recessive inheritance of the trait. Whole-genome sequencing of an affected dog revealed 12 protein-changing variants that were not present in 566 control genomes, of which two were located in functional candidate genes, FYCO1 and CRYGB. Targeted genotyping of both variants in the investigated family excluded CRYGB and revealed perfect co-segregation of the FYCO1 variant with the juvenile cataract phenotype. This variant, FYCO1:c.2024delG, represents a 1 bp frameshift deletion predicted to truncate ~50 of the open reading frame p.(Ser675Thrfs*5). FYCO1 encodes the FYVE and coiled-coil domain autophagy adaptor 1, a known regulator of lens autophagy, which is required for the normal homeostasis in the eye. In humans, at least 37 pathogenic variants in FYCO1 have been shown to cause autosomal recessive cataract. Fcyo1−/− knockout mice also develop cataracts. Together with the current knowledge on FYCO1 variants and their functional impact in humans and mice, our data strongly suggest FYCO1:c.2024delG as a candidate causative variant for the observed juvenile cataract in Wirehaired Pointing Griffon dogs. To the best of our knowledge, this study represents the first report of a FYCO1-related cataract in domestic animals.

Item Type:

Journal Article (Original Article)

Division/Institute:

09 Interdisciplinary Units > Next Generation Sequencing (NGS) Platform
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Rudd Garcés, Gabriela; Christen, Matthias Theo; Jagannathan, Vidya and Leeb, Tosso

Subjects:

500 Science > 590 Animals (Zoology)
600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2073-4425

Publisher:

MDPI, Molecular Diversity Preservation International

Language:

English

Submitter:

Tosso Leeb

Date Deposited:

04 Mar 2022 14:20

Last Modified:

01 Jun 2022 14:53

Publisher DOI:

10.3390/genes13020334

PubMed ID:

35205377

BORIS DOI:

10.48350/165559

URI:

https://boris.unibe.ch/id/eprint/165559

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