ABSTRACT
This chapter reviews the principles of forward genetic selections in mammalian cell models for discovering the genes contributing to complex phenotypes associated with human disease. It discusses nucleic acid-based technology platforms for validating genes and confirming their biological roles. The chapter focuses on the need for an integrated approach to gene discovery involving both forward genetic and reverse genetic strategies to unravel the complexity of human disease and identifies relevant target genes for drug discovery. One of the most effective ways of identifying genes controlling complex cellular phenotypes and biological mechanisms of human disease is the use of chemical mutagenesis and forward genetic selections for modified phenotypes. Classical genetic approaches have been used in model organisms to determine the mechanisms responsible for gain or loss of gene functions. The chapter examines the range and diversity of gain-of-function and loss-of-function genetic screens and selections reported in mammalian cells.
