A bioinformatics-based strategy identifies c-Myc and Cdc25A as candidates for the Apmt mammary tumor latency modifiers
A bioinformatics-based strategy identifies c-Myc and Cdc25A as candidates for the Apmt mammary tumor latency modifiers
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DOI：
10.1101/gr.210502
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发表时间：
2002-06-01
期刊：
影响因子：
7
通讯作者：
Hunter, KW
中科院分区：
文献类型：
--
作者：
Cozma, D;Lukes, L;Hunter, KW
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. Oil 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 polymorph isms 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 Apmt1 and Apmt2, and suggest that, at least in certain instances, bioinformatics can be utilized to bypass congenic construction and subsequent mapping in conventional QTL studies.
