SUPR
Collie PRA
Dnr:

NAISS 2024/22-87

Type:

NAISS Small Compute

Principal Investigator:

Suvi Mäkeläinen

Affiliation:

Sveriges lantbruksuniversitet

Start Date:

2024-01-26

End Date:

2025-01-01

Primary Classification:

10203: Bioinformatics (Computational Biology) (applications to be 10610)

Webpage:

Allocation

Abstract

Inherited retinal degenerations (IRDs) lead to visual impairment and blindness in both dogs and humans. IRDs are a group of different, mostly monogenic diseases that follow a Mendelian inheritance pattern, and most of the IRDs are autosomal recessive. Multiple dog breeds have been shown to be affected by different genetic variants leading to distinctive forms of IRD. As of today, approximately 300 genes and mutations have been shown to be involved in human IRDs, but only 30 genes and mutations have been found to cause IRDs in dogs. Therefore, there is a large interest in finding additional genes that are involved in canine IRDs and that could be used to model the human equivalent that is caused by a human orthologous gene. One of the affected dog breeds is Collie, which is affected by a type of IRD called progressive retinal atrophy (PRA). The affected individuals typically develop clinical signs at the age of 5-6 years of age, starting with problems in dim-light conditions and gradually worsening visual impairment that later affects vision also in day-light conditions. Multiple known mutations are known to cause PRA in dogs, and we have previously tested wether these known mutations would cause the disease in collie, but the conditions has proven to be a novel form of PRA where the causative genetic variant is unknown. We have therefore generated whole-genome sequence data (Illumina short-read sequencing) from five collie dogs, including two affected males, their unaffected female sibling and their unaffected parents. The data was generated using the Novaseq 6000 platform at the SNP&SEQ Technology Platform at Uppsala University. To analyse the data, we have previously (NAISS 2023/23-30/NAISS 2023/22-72) built and updated a whole-genome sequence analysis workflow using the new canine reference genome CanFam4. The aim of this project is to analyse the collie WGS data to identify a causative genetic variant that is the reason for the PRA in the breed. If successful, the results will be published in a scientific journal and thereafter developed into a genetic test that allows the breeders to make informed breeding decisions so that no affected dogs are born in the future. Depending on the nature of the mutation and affected gene, the results can also be used to model and aid the human IRD results.