Grant: Operating Grant

Amazing advances in our ability to sequence genomes has revealed the astounding genetic diversity between different people. Biomedical researchers are now faced with a daunting challenge - how to assign function to the thousands of genes in our genomes and to understand how differences between genes contribute to disease. It is clear that our genomes can usually tolerate single genetic lesions - a phenomenon called genetic buffering - and that most complex diseases like cancer are caused by interactions between different genetic variants. We have established an internationally unique platform for performing automated genetic screens using a premier model system for studying genetics, the budding yeast. We have used our platform to produce the first genetic interaction maps for any organism, and have used this information to predict how genes interact in other organisms, including humans. We now propose to apply our expertise to understanding how the duplication of genes - which is rampant in our genomes - contributes to genetic buffering and to the appearance of new functions for genes. Our project involves systematic mapping of interactions involving mutation of duplicate genes and other genes in the genome. Our work will provide a key for addressing and explaining a number of long-standing genetic concepts, that have not been tested, due to a dearth of useful data. Our map of complex genetic interactions will provide unique data that will enable biomedical researchers to understand how the content of our genomes is shaped, and how that relates to complex diseases.