Exploring the effects of polymorphisms on cis-regulatory signal transduction response.
Bottom Line: cis-Regulatory sequences (CRSs) direct cell-specific and inducible gene expression in response to signal transduction networks, and it is becoming apparent that many cases of disease susceptibility and drug response stratification are due to polymorphisms that alter CRS responses in a context-dependent manner.The technologies described build on the successes of ENCODE (ENCyclopedia Of DNA Elements) by exploring the effects of polymorphisms on CRS context dependency.This understanding is essential to uncover the genomic basis of disease susceptibility and will play a major role in delivering on the promise of personalized medicine.
Affiliation: Gene Regulatory Systems Laboratory, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland AB25 2ZD, UK. email@example.comShow MeSH
Mentions: The main obstacle to understanding the mechanisms that affect CRS activity has been our inability to identify them. In the past, identifying CRSs has relied on the painstaking deletion analysis of gene flanking regions. However, thanks to the sequencing of the human genome and the availability of ever more rapid advances in high-throughput sequencing technologies, several more rapid and effective high-throughput solutions have been devised to find and characterize CRSs (summarized in Box 1 and Figure 2).
Affiliation: Gene Regulatory Systems Laboratory, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland AB25 2ZD, UK. firstname.lastname@example.org