Kristopher JL Irizarry, Natalie Punt, Randall Bryden, Joseph Bertone and Yvonne Drechsler
We utilized a comparative genomics approach to analyze a core set of tumorigenesis orthologs among human, mouse, dog and naked mole rat. The analysis identified cancer orthologs that are both conserved and divergent between dog and the cancer resistant species naked mole rat. These tumorigenesis orthologous are associated with phenotypes that modulate cancer susceptibility, cardiac development, craniofacial development, brain development, skeletal development, and immune function, to name a few. This bioinformatics approach employed a variety of literature mining tools to further uncover relationships between the tumorigenesis orthologs. Together, these results shed light on the relationship between breed formations, breed associated morphological traits and breed associated susceptibility to tumorigenesis. These findings support the use of a comparative genomic analysis between species with dramatically different disease phenotypes as a gene discovery tool. A total of 146 proteins coding SNPs were identified in these tumorigenesis orthologs representing missense variations, frame shift variations and nonsense variations. The genes identified in this study can serve as a list of candidates for subsequent laboratory and clinical study. Furthermore, the identification of SNPs impacting the primary structure of the tumorigenesis orthologs may provide clues about the basis of cancer susceptibility between dog breeds.
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