@article{Cozma01062002, author = {Cozma, Diana and Lukes, Luanne and Rouse, Jessica and Qiu, Ting Hu and Liu, Edison T. and Hunter, Kent W.}, title = {A Bioinformatics-Based Strategy Identifies c-Myc and Cdc25A as Candidates for the Apmt Mammary Tumor Latency Modifiers}, volume = {12}, number = {6}, pages = {969-975}, year = {2002}, doi = {10.1101/gr.210502}, abstract ={The epistatically interacting modifier loci (Apmt1 and Apmt2) accelerate the polyoma Middle-T (PyVT)-induced mammary tumor. To identify potential candidate genes loci, a combined bioinformatics and genomics strategy was used. On the basis of the assumption that the loci were functioning in the same or intersecting pathways, a search of the literature databases was performed to identify molecular pathways containing genes from both candidate intervals. Among the genes identified by this method were the cell cycle-associated genes Cdc25A and c-Myc, both of which have been implicated in breast cancer. Genomic sequencing revealed noncoding polymorphism in both genes, in the promoter region of Cdc25A, and in the 3′ UTR of c-Myc. Molecular and in vitro analysis showed that the polymorphisms were functionally significant. In vivo analysis was performed by generating compound PyVT/Myc double-transgenic animals to mimic the hypothetical model, and was found to recapitulate the age-of-onset phenotype. These data suggest that c-Myc and Cdc25A are Apmt1and Apmt2, and suggest that, at least in certain instances, bioinformatics can be utilized to bypass congenic construction and subsequent mapping in conventional QTL studies.}, URL = {http://genome.cshlp.org/content/12/6/969.abstract}, eprint = {http://genome.cshlp.org/content/12/6/969.full.pdf+html}, journal = {Genome Research} }