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The Importance Of Charting Genetic Interactions On A Mammalian Cell

Decent Essays

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 …show more content…

But only a modest fraction of interactions are tested (Lee et al., 2004; Lee et al., 2008).

Our understanding of mammalian genetic interactions is even less impressive. Large-scale efforts to map the protein interactome in humans have begun (Gandhi et al., 2006). But only about 10% of potential interactions have been evaluated (Rual et al., 2005; Venkatesan et al., 2009). Furthermore, genetic interactions in humans and mammals remain unexplored. The overlap between human, yeast, C. elegans, and fly protein interaction networks is small (Gandhi et al., 2006). Hence, it is necessary to explore mammalian genetic interactions in the mammalian setting. A problem for mammalian cells is the lack of a simple and cheap method for combining alleles of distinct genes in the same cell.

Our hypothesis is that mammalian cells must thrive by exploiting combinations of genes, in fact, genetic networks that both protect the cell from destruction and enhance its survival. We believe these networks involve genes that tend to be coordinated in their copy number alterations (CNAs), even when they are located at a distance on the genome. Our recent work studying genetic networks that exist within libraries of radiation hybrid (RH) cells have elucidated key survival-enhancing interactions with remarkable specificity (Lin et al., 2010). This work identified genetic interactions with close to single gene

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