Canine genomic resources have improved substantially since inception of the Dog Aging Project (DAP), including the recent release of a new, high-contiguity canine reference genome. DAP's current sequencing strategy ? low-pass sequencing followed by imputation ? is inexpensive and provides the high density of genomic variant calls needed for well-powered genome-wide association studies. However, it relies on imputation of single nucleotide variants (SNPs) and short indels, an approach which may miss specific variants that are of particular interest as causal candidates. Most notably, larger-scale structural variants (SVs), some already causally associated with canine traits, cannot be accurately discerned without additional sequencing. We propose to update DAP processes to yield far more complete genetic information for each dog sequenced, at no additional cost per dog.
Our specific aims i nclude: (1) expand and improve the existing canine imputation panel, using the latest canine genome reference and additional canine samples; (2) develop a structural variant imputation panel to support the imputation of canine structural variants from canine short variants; (3) integrate targeted high-coverage sequencing into the low-pass sequencing process, allowing us to directly call variants at high-priority loci without imputation, and improve our sensitivity to rare and even de novo variants. Collectively, these improvements will allow the Dog Aging Project to more effectively identify genes, regulatory regions and specific variants associated with longevity and age-related disease. By also sharing these improvements with the canine research community, we will support ongoing studies into a broad range of age-related diseases, including neurodegenerative diseases, organ failure, and cancer.
Since the launch of the Dog Aging Project, advances in genome technology have improved the quality and completeness of the canine reference genome, and many more dogs from all around the world have had their genomes sequenced. By incorporating these new resources into the Dog Aging Project, we will enhance the existing process for genetic analysis to produce higher quality and more complete information on each dog. This will add value to the Dog Aging Project by making dogs an even more powerful model for investigating the genetics of aging, and support canine research projects worldwide.
