Chapter 6 - Functional Genomics

Abstract

The completion of the human genome project marked the beginning of the so-called postgenomic era, an exciting time that is delivering new insights into the complex regulation of genes in all fields of research, including bone biology. The rapid development of new tools of functional genomics, and major efforts, such as the ENCODE consortium led to the discovery of hundreds of thousands of regulatory elements throughout the genome using methods, such as DNase-seq and ChIP-seq. Novel approaches are needed to probe the actual function of these annotated sequences and to understand the function of variants identified by genome-wide association studies, particularly in the bone field. Examples for these tools, such as RNAi-based assays, multiplexed reporter assays to assess the function of genomic variants, and genome-wide gain-of-function screens using the ORFeome are discussed. The CRISPR/CAS9 technology with applications, such as saturating mutagenesis and gain- and loss-of-function screens is revolutionizing functional genomics.