Abstract IA19: Canine cancer genetics: What dogs can tell us about ourselves

Abstract

Abstract The 165 domestic US dogs breeds display tremendous morphologic variation, making them an appealing model for the identification of genetic regulators of vertebrate shape and development and disease susceptibility. We have genotyped over 1000 dogs representing 85 domestic breeds to generate a reference dataset on over 60,000 informative SNPs per dog. This, combined with morphometric data has allowed us to map and sequence loci that control various features of breed-specific traits related to shape and size. In addition to helping us understand the genetics of morphologic variation, the underlying loci have also helped us understand the genetics of growth regulation. We now have a clearer sense of how variation is created in body size, leg length, head shape and other features that define various breeds of dog because of such studies. The domestic dog is also a robust model for studying the genetics of disease susceptibility as some breeds harbor an elevated risk, particularly for types of cancer, in spite of a relatively simple genetic architecture that is common to all dogs. One example of breed-specific disease propensity is squamous cell carcinoma of the digit (SCCoD), a locally aggressive cancer that frequently causes lytic bone lesions and multiple toe recurrence. SCCoD is uncommon in most dog breeds, but occurs in Schnauzers, Briards, and Standard Poodles, who are at about a 10-fold increased risk. Another cancer of interest to humans and dogs is transitional cell carcinoma of the bladder, which we observe at increased risk in Scottish Terriers (22 fold increased risk), West Highland White Terriers and Shelties. A final example is histiocytic carcinoma, which is common to Flat Coated Retrievers and Bernese Mountain dogs. Advances in genomic technologies, together with valued clinical collaborations, have allowed us to undertake studies aimed at understanding the genetic susceptibility of each. Key to advancing these studies has been the availability of dense SNP chips and the ever-increasing amount of data on a variety of dog breeds. We will report on our progress on each. Citation Format: Elaine A. Ostrander. Canine cancer genetics: What dogs can tell us about ourselves. [abstract]. In: Proceedings of the AACR Special Conference: The Translational Impact of Model Organisms in Cancer; Nov 5-8, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(11 Suppl):Abstract nr IA19.