The Importance Of Charting Genetic Interactions On A Mammalian Cell

789 WordsOct 8, 20144 Pages
RESEARCH STRATEGY A. SIGNIFICANCE Charting genetic interactions in a mammalian cell will help us understand normal cell processes. A map of interactions will also pinpoint what goes wrong in diseases like cancer. But deciphering the genetic circuitry of the mammalian cell remains a daunting challenge. One major obstacle to annotating genetic interactions is their number. In a genome of 20,000 genes, there are 2 x 108 possible pairwise interactions. Either gene-gene or protein-protein interactions can be used to unravel molecular networks. In yeast, scientists employ synthetic genetic array analysis to map gene interactions (Costanzo et al., 2010; Tong et al., 2001; Tong et al., 2004). In Caenorhabditis elegans, they use RNA interference (Lehner et al., 2006). Yeast two-hybrid mapping or co-affinity immunoprecipitation has been used to catalog protein interactions (Cusick et al., 2005; Rual et al., 2005) in yeast, C. elegans, and Drosophila melanogaster (Gavin et al., 2006; Giot et al., 2003; Li et al., 2004; Simonis et al., 2009; Yu et al., 2008). However, gene and protein interactions are tested one at a time. The assays are laborious and expensive. Mapping interactions for the whole genome requires enormous resources. The methods do not provide simple yardsticks of confidence and there is no information on the biological consequences of protein binding. The assays also suffer from high false-positive and false-negative rates, that can approach 50%. Probabilistic
Open Document