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

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...
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Autor*in:	Philip Cowie [verfasserIn] Ruth Ross [verfasserIn] Alasdair MacKenzie [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2013

Schlagwörter:	gene regulation cis-regulatory variation non-coding DNA chromatin signal transduction drug response stratification cell specificity context dependency ENCODE consortium

Übergeordnetes Werk:	In: Biology - MDPI AG, 2012, 2(2013), 1, Seite 64-84
Übergeordnetes Werk:	volume:2 ; year:2013 ; number:1 ; pages:64-84

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/biology2010064

Katalog-ID:	DOAJ017411955

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authorswithroles_txt_mv	Philip Cowie @@aut@@ Ruth Ross @@aut@@ Alasdair MacKenzie @@aut@@
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callnumber-first	Q - Science
author	Philip Cowie
spellingShingle	Philip Cowie misc QH301-705.5 misc gene regulation misc cis-regulatory variation misc non-coding DNA misc chromatin misc signal transduction misc drug response stratification misc cell specificity misc context dependency misc ENCODE consortium misc Biology (General) Understanding the Dynamics of Gene Regulatory Systems; Characterisation and Clinical Relevance of cis-Regulatory Polymorphisms
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topic_title	QH301-705.5 Understanding the Dynamics of Gene Regulatory Systems; Characterisation and Clinical Relevance of cis-Regulatory Polymorphisms gene regulation cis-regulatory variation non-coding DNA chromatin signal transduction drug response stratification cell specificity context dependency ENCODE consortium
topic	misc QH301-705.5 misc gene regulation misc cis-regulatory variation misc non-coding DNA misc chromatin misc signal transduction misc drug response stratification misc cell specificity misc context dependency misc ENCODE consortium misc Biology (General)
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title	Understanding the Dynamics of Gene Regulatory Systems; Characterisation and Clinical Relevance of cis-Regulatory Polymorphisms
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title_sort	understanding the dynamics of gene regulatory systems; characterisation and clinical relevance of cis-regulatory polymorphisms
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title_auth	Understanding the Dynamics of Gene Regulatory Systems; Characterisation and Clinical Relevance of cis-Regulatory Polymorphisms
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.
abstractGer	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.
abstract_unstemmed	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.
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title_short	Understanding the Dynamics of Gene Regulatory Systems; Characterisation and Clinical Relevance of cis-Regulatory Polymorphisms
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Understanding the Dynamics of Gene Regulatory Systems; Characterisation and Clinical Relevance of cis-Regulatory Polymorphisms

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