Largely due to their population genetics, dogs are uncommonly powerful animal models of human disease. Recent advances have spawned a new era of dog genetics. Here we add an important tool to the canine genetics toolbox: DNA copy number genetics. In normal humans, thousands of gene-spanning Copy Number Variants (CNVs) were recently identified. Some of these have been shown to have strong roles in disease predisposition. We will use state of the art methods to create the first high resolution CNV map of the dog genome. We have validated the technology and find a level of >50 kb copy number variation that is similar to that reported for primates and rodents. We will molecularly define a high-priority set of CNVs and determine their frequencies in a second panel of dogs. Our work will enable the identification of breed-specific microdeletions and other CNVs that are associated with disease susceptibility and diverse traits. In future studies Single Nucleotide Polymorphisms (SNPs) in linkage disequilibrium with these CNVs can be used to genotype them. Thus our resource and the canine 27k SNP platforms under development will be complementary. We will co-ordinate with other centers to assemble web based distribution of CNV data and maps.
Natural diseases of dogs offer outstanding animal models from which to learn about human disease. Here we propose to develop powerful new approaches and resources for finding dog disease genes. We expect this work will lead to improved health care in dogs, and to the improved understanding of human disease mechanisms.
| Vucic, Emily A; Thu, Kelsie L; Robison, Keith et al. (2012) Translating cancer 'omics' to improved outcomes. Genome Res 22:188-95 |
| Enfield, Katey S S; Stewart, Greg L; Pikor, Larissa A et al. (2011) MicroRNA gene dosage alterations and drug response in lung cancer. J Biomed Biotechnol 2011:474632 |
| Cottrell, Catherine E; Bir, Natalie; Varga, Elizabeth et al. (2011) Contactin 4 as an autism susceptibility locus. Autism Res 4:189-99 |
| Rowell, Jennie L; McCarthy, Donna O; Alvarez, Carlos E (2011) Dog models of naturally occurring cancer. Trends Mol Med 17:380-8 |
| Chari, Raj; Thu, Kelsie L; Wilson, Ian M et al. (2010) Integrating the multiple dimensions of genomic and epigenomic landscapes of cancer. Cancer Metastasis Rev 29:73-93 |
