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 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.
|
Authors | Diana Cozma, Luanne Lukes, Jessica Rouse, Ting Hu Qiu, Edison T Liu, Kent W Hunter |
Journal | Genome research
(Genome Res)
Vol. 12
Issue 6
Pg. 969-75
(Jun 2002)
ISSN: 1088-9051 [Print] United States |
PMID | 12045150
(Publication Type: Journal Article)
|
Chemical References |
- Genetic Markers
- Proto-Oncogene Proteins c-myc
- CDC25A protein, human
- Cdc25a protein, mouse
- cdc25 Phosphatases
|
Topics |
- 3T3 Cells
- Animals
- Computational Biology
(methods)
- Epistasis, Genetic
- Genes, myc
(genetics)
- Genetic Markers
(genetics)
- Humans
- Mammary Neoplasms, Experimental
(enzymology, genetics)
- Mice
- Mice, Transgenic
- Proto-Oncogene Proteins c-myc
(genetics)
- Quantitative Trait, Heritable
- cdc25 Phosphatases
(genetics)
|