Presenter Thomas Simon
Authors Thomas Simon (1), Suvi Mäkeläinen (1), Daniel Goncalves (2), Björn Ekesten (2), Tomas F. Bergström (1)
Affiliations 1. Department of Animal Biosciences, Swedish University of Agricultural Sciences, Uppsala, Sweden, 2. Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
Presentation Type Talk
Abstract
Inherited retinal degenerations (IRDs) are a diverse group of progressive diseases that cause visual impairment and blindness in both humans and dogs. They represent a heterogeneous group of genetic disorders, characterized by variable ages of onset, rates of progression, and modes of inheritance. Most of the IRDs are inherited in an autosomal recessive manner, although autosomal dominant and X-linked forms have also been described. To date, 367 causative genes have been identified in humans, while only about 30 have been reported in dogs.
A novel form of IRD has recently been observed in Rough Collies. A genetic variant (22 bp insertion) in the gene RD3 regulator of GUCY2D (RD3) has previously been described to cause rod–cone dysplasia type 2 (rcd2) in the breed. However, the novel IRD cannot be explained by the RD3 insertion or by any of the known genetic variants in dogs. To investigate the genetic cause, we performed family-sequencing of five dogs. This included both the unaffected parents as well as three offspring, of which two were affected males and one unaffected female.
After variant calling and annotation, conditional filtering was conducted under the assumption of either an autosomal recessive or an X-linked mode of inheritance. To further restrict the number of candidate variants, we filtered away common variation using publicly available data. The possible impact of the identified candidate variants in the coding sequence was predicted using SIFT and PolyPhen-2. In addition, variants were further investigated using PhyloP conservation scores and manual curation based on gene function. The results of this ongoing study will be presented.