Research

    Progress in the field of genetics and genomics in all mammalian species has resulted in a wealth of tools and resources that are critical to identifying genes and sequence changes that underly traits or diseases. ​

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    Since the mapping of the Progressive Rod-Cone Degeneration(PRCD) retinal disease locus in 1998, our research group at PennVet has made substantial progress in first characterizing a number of inherited retinal diseases in dogs, identifying the responsible gene and mutation, and subsequently developing DNA-based tests to identify genetically normal, carrier and affected dogs. ​

    Nineteen disease causing genes and mutations have been identified by our team, some of which affect multiple breeds. In fact, the same prcd-gene mutation affects 52 different breeds of varied geographic origins.

    From 1998 until 2010 canine genetic studies were mainly done using a pedigree-based approach where dogs with known inherited diseases were initially tested using linkage analysis followed by the time-consuming approach of positional cloning the candidate gene once the genomic region of interest was found.

    To do this work required sufficiently large families of dogs in which every member was established to be affected, and non-affected, and, if possible, the non-affected dogs classified as genetically normal or carriers (for recessively inherited traits), and knowledge of the mode of inheritance.​

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    Now most genetics studies involve generation of genetic markers for genome-wide association studies (GWAS) combined with whole genome sequencing (WGS) to map traits/diseases of interest to a genomic region (using GWAS) followed by careful analysis of the sequences in the candidate region using WGS.​

    It is no longer required to use family groupings for GWAS, and unrelated or not closely related dogs having the same inherited disease can be used along with unaffected controls. ​

    Markers generated for GWAS are also very important for other mapping methods based on identity-by-descent (IBD), especially if a small group of related dogs is involved.​

    Once a candidate region is identified, whole genome sequencing will pick up all the candidate variants possibly associated with the disease.​

    Candidate variants are then tested within the population of available controls. For this reason, communication with veterinarians and breeders of the affected breed is vital, as well as the maintenance of a well-organized sample archive which can be used to check the frequency of any candidate variant to keep pursuing it or exclude it.​

    Publicly available databases are also used to verify the presence of any candidate variant – if a promising mutation is frequent in a large group of unrelated dogs, there is a low chance that is the one associated with a novel pathological condition.​

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    Our Genomic Data Flow and  Data Analysis pipeline

    Communication with owners and breeders, access to certified veterinarian ophthalmologists and constant upkeep of our archive are essential tools for our discoveries.

    Our bioinformatics strategies focus on the identification of regions of interest within the canine genome, for then focus of these regions with sequencing technologies.