A Novel Yeast Genomics Method for Identifying New Breast Cancer Susceptibility Genes

We are attempting to identify novel genes in the yeast S. cerevisiae that confer gross chromosomal instability GCI a hallmark of most breast cancers when deleted. Using a collection of yeast strains carrying the deletion of a unique open reading frame, we have transfected a yeast artificial chromosome YAC as a reporter for GCI frequency to determine the quantitative impact of the loss of each gene function. We have constructed the redesigned reporter with all of the components for selection and maintenance. The URA3 gene results in sensitivity to 5-FOA and the methionine regulated BAX gene induces apoptosis in yeast in individual and pooled deletion strains, and the NatMX nourseothricin resistance marker for YAC retention... We have introduced the YAC by mating into the entire collection of deletion strains and are currently running the pooled growth assay to identify genes affecting GCI. The mammalian orthologs of the resulting candidate genes methods. There is a crucial need to find new candidate genes for breast cancer susceptibility in women and identifying these human genes can further improve monitoring and treatment guidelines for women with these mutations.