Next Article in Journal
Isolation and Characterization of Bacteria from Ancient Siberian Permafrost Sediment
Next Article in Special Issue
PRDM Proteins: Molecular Mechanisms in Signal Transduction and Transcriptional Regulation
Previous Article in Journal
BRCA1 and Its Network of Interacting Partners
Previous Article in Special Issue
Gene Expression and Regulation in Adrenocortical Tumorigenesis
Article Menu

Export Article

Open AccessReview
Biology 2013, 2(1), 64-84; doi:10.3390/biology2010064

Understanding the Dynamics of Gene Regulatory Systems; Characterisation and Clinical Relevance of cis-Regulatory Polymorphisms

School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, AB25 2ZD, UK
*
Author to whom correspondence should be addressed.
Received: 1 November 2012 / Revised: 21 December 2012 / Accepted: 4 January 2013 / Published: 9 January 2013
(This article belongs to the Special Issue Gene Expression and Regulation)
View Full-Text   |   Download PDF [938 KB, uploaded 9 January 2013]   |  

Abstract

Modern genetic analysis has shown that most polymorphisms associated with human disease are non-coding. Much of the functional information contained in the non-coding genome consists of cis-regulatory sequences (CRSs) that are required to respond to signal transduction cues that direct cell specific gene expression. It has been hypothesised that many diseases may be due to polymorphisms within CRSs that alter their responses to signal transduction cues. However, identification of CRSs, and the effects of allelic variation on their ability to respond to signal transduction cues, is still at an early stage. In the current review we describe the use of comparative genomics and experimental techniques that allow for the identification of CRSs building on recent advances by the ENCODE consortium. In addition we describe techniques that allow for the analysis of the effects of allelic variation and epigenetic modification on CRS responses to signal transduction cues. Using specific examples we show that the interactions driving these elements are highly complex and the effects of disease associated polymorphisms often subtle. It is clear that gaining an understanding of the functions of CRSs, and how they are affected by SNPs and epigenetic modification, is essential to understanding the genetic basis of human disease and stratification whilst providing novel directions for the development of personalised medicine. View Full-Text
Keywords: gene regulation; cis-regulatory variation; non-coding DNA; chromatin; signal transduction; drug response stratification; cell specificity; context dependency; ENCODE consortium gene regulation; cis-regulatory variation; non-coding DNA; chromatin; signal transduction; drug response stratification; cell specificity; context dependency; ENCODE consortium
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Cowie, P.; Ross, R.; MacKenzie, A. Understanding the Dynamics of Gene Regulatory Systems; Characterisation and Clinical Relevance of cis-Regulatory Polymorphisms. Biology 2013, 2, 64-84.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Biology EISSN 2079-7737 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top