Many Kissed Frogs and a Few Princes: Searching Dog Genomes for Causal Variants, Incidental Findings, and Reverse Genetics Associations

Since 2010 our team of molecular geneticists and veterinary specialists have been partially successful in our efforts to identify disease-causing alleles in whole genome sequences (WGS) from dogs with heritable diseases. Sequencing data was generated using Illumina HiSeq 2500 and Illumina HiSeq X Ten platforms for 87 dogs of 50 breeds and 53 disease phenotypes. A database containing over 150k canine DNA samples representing a large variety of breeds and disease is available for potential variant validation and association. So far, disease-associated mutations have been successfully identified for 18 disease phenotypes in 15 different breeds through varied analysis approaches. The successes include: paroxysmal dyskinesia in Soft Coated Wheaten Terriers, different forms of neuronal ceroid lipofuscinosis, GM2-gangliosidosis in the Shiba Inu, dilated cardiomyopathy in Standard Schnauzers, and spinocerebellar ataxia in Jack Russel Terriers, among others. I will describe examples of some strategies that have led to the identification of causal variants and also discuss some examples where the causes have not yet been identified. In addition, I will describe our experiences with incidental findings (phenotypes unrelated to the targeted disease but predicted to occur in the sequenced individual) and our efforts to find reverse genetic association (phenotypes unrelated to the targeted disease but predicted to occur in relatives of sequenced individual).