DISEASE GENE DISCOVERY THROUGH INTEGRATIVE GENOMICS

Ke yW ords human genetics, positional cloning, functional genomics, machine learning ■ Abstract The availability of complete genome sequences and the wealth of large- scale biological data sets now provide an unprecedented opportunity to elucidate the genetic basis of rare and common human diseases. Here we review some of the emerg- ing genomics technologies and data resources that can be used to infer gene function to prioritize candidate genes. We then describe some computational strategies for integrat- ing these large-scale data sets to provide more faithful descriptions of gene function, and how such approaches have recently been applied to discover genes underlying Mendelian disorders. Finally, we discuss future prospects and challenges for using integrative genomics to systematically discover not only single genes but also entire gene networks that underlie and modify human disease.