ICCFGG 2022
#50 Whole genome sequencing to investigate upper urinary tract stone formation in normocalcemic domestic shorthair cats Rebecca Geddes1 , Marsha Wallace1,2, Jonathan Elliott3, Harriet Syme1, 99 Lives Consortium, Lucy Davison1,2 rgeddes@rvc.ac.uk 1Clinical Sciences and Services, Royal Veterinary College, Hatfield, UK, 2Wellcome Centre for Human Genetics, University of Oxford, UK, 3Comparative Biomedical Sciences, Royal Veterinary College, London, UK Introduction Upper urinary tract stones (UUTS), predominantly calcium-based, affect 10-20% of humans, and 5% of cats seen at the Royal Veterinary College referral hospital. Affected cats are usually normocal- cemic and majority domestic shorthaired (DSH). A monogenic cause is found in 15-17% of affected human patients. Objective To reveal genetic variants associated with feline UUTS in normocalcemic cats. Materials and Methods DNA was extracted from normocalcemic DSH cats and whole genome sequencing (WGS) performed using the Illumina platform (NovaSeq 6000). Cases (n=6) were diagnosed with UUTS under 7 years of age. Controls (n=6) were ‚â• 12 years, non-azotemic, with no UUTS on imaging. A bespoke bioinformatics workflow was used to perform quality control (FASTQC & Sickle), mapping to the reference genome (BWA), variant calling (GATK 4), allele frequency calculation and statistics (PLINK), and annotation. Potential monogenic variants associated with UUTS were initially identi- fied. Ongoing analysis will explore and prioritise variants associated with UUTS as a complex trait. Results Thirty-two candidate monogenic variants show promise due to their presence in genes associated with stone formation or renal disease in humans, their moderate or high impact and their alternate allele frequencies in cases versus controls. Approximately 3000 identified variants have been prior- itised using both additive and recessive models of association with feline UUTS. A follow-up study utilising targeted sequencing in a larger case-control cohort is underway. Conclusion WGS has identified novel candidate variants associated with UUTS in cats. Further genotyping will help to establish whether UUTS may have monogenic inheritance in some cats.
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