Disease Gene Identification

Anup K. Nair, Leslie J. Baier

The genomic era, highlighted by large scale, genome-wide association studies (GWAS) for both common and rare diseases, have identified hundreds of disease-associated variants. However, most of these variants are not disease causing, but instead only provide information about a potential proximal functional variant through linkage disequilibrium. It is critical that these functional variants be identified, so that their role in disease risk can be ascertained. Luciferase assays are an invaluable tool for identifying and characterizing functional variants, allowing investigations of gene expression, intracellular signaling, transcription factors, receptor activity, and protein folding. In this chapter, we provide an overview of the different ways that luciferase assays can be used to validate functionality of a variant.