In silico detection of sequence variations modifying transcriptional regulation.

PLoS Computational Biology
Malin C AndersenJacob Odeberg

Abstract

Identification of functional genetic variation associated with increased susceptibility to complex diseases can elucidate genes and underlying biochemical mechanisms linked to disease onset and progression. For genes linked to genetic diseases, most identified causal mutations alter an encoded protein sequence. Technological advances for measuring RNA abundance suggest that a significant number of undiscovered causal mutations may alter the regulation of gene transcription. However, it remains a challenge to separate causal genetic variations from linked neutral variations. Here we present an in silico driven approach to identify possible genetic variation in regulatory sequences. The approach combines phylogenetic footprinting and transcription factor binding site prediction to identify variation in candidate cis-regulatory elements. The bioinformatics approach has been tested on a set of SNPs that are reported to have a regulatory function, as well as background SNPs. In the absence of additional information about an analyzed gene, the poor specificity of binding site prediction is prohibitive to its application. However, when additional data is available that can give guidance on which transcription factor is involved in the...Continue Reading

References

Jul 1, 1991·Molecular and Cellular Biology·N F CunniffW D Morgan
Jul 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·G D Stormo, M Yoshioka
Nov 2, 1995·The New England Journal of Medicine·P J BosmaR P Oude Elferink
Jan 1, 1996·Molecular and Cellular Biology·J W Fickett
Aug 15, 1997·Journal of Molecular Biology·D S FieldsG D Stormo
May 17, 2000·Bioinformatics·G D Stormo
Jun 17, 2000·Baillière's Best Practice & Research. Clinical Haematology·P J Grant, S E Humphries
Oct 4, 2000·Nature Genetics·W W WassermanC E Lawrence
Oct 18, 2000·Proceedings of the National Academy of Sciences of the United States of America·D CavalieriD L Hartl
Jan 11, 2000·Nucleic Acids Research·S T SherryK Sirotkin
Dec 4, 2001·Genome Research·B LenhardW W Wasserman
Aug 15, 2002·Bioinformatics·Boris Lenhard, Wyeth W Wasserman
Oct 9, 2002·Genome Research·Jason E StajichEwan Birney
Nov 1, 2002·Nature Genetics·Christopher R CowlesEric S Lander
Nov 2, 2002·Molecular Biology and Evolution·Matthew V Rockman, Gregory A Wray
Nov 7, 2002·Biological & Pharmaceutical Bulletin·Chikako KurikiKiyoto Motojima
Jan 10, 2003·Nucleic Acids Research·D KarolchikUNKNOWN University of California Santa Cruz
Jan 10, 2003·Nucleic Acids Research·V MatysE Wingender
Feb 15, 2003·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·G ArgyropoulosC Bouchard
Apr 1, 2003·Nature Genetics·Thomas J Hudson
May 23, 2003·Journal of Biology·Boris LenhardWyeth W Wasserman
Oct 30, 2003·Physiological Genomics·Tomi PastinenThomas J Hudson
Dec 19, 2003·Nucleic Acids Research·Albin SandelinBoris Lenhard
Dec 19, 2003·Nucleic Acids Research·D FredmanA J Brookes
May 4, 2004·Journal of Medical Genetics·F BaiG Argyropoulos
May 8, 2004·Nature Reviews. Genetics·Wyeth W Wasserman, Albin Sandelin
May 18, 2004·Human Mutation·Tao ZhaoGary D Stormo
Jul 23, 2004·Nature·Michael MorleyVivian G Cheung
Oct 23, 2004·Science·Tomi Pastinen, Thomas J Hudson
Jun 4, 2005·Nucleic Acids Research·Shannan J Ho SuiWyeth W Wasserman
Jul 19, 2005·Genome Research·Adam SiepelDavid Haussler
Aug 9, 2005·Human Mutation·Paul R BucklandMichael C O'Donovan
Aug 27, 2005·PLoS Genetics·James RonaldLeonid Kruglyak
Aug 30, 2005·Molecular & Cellular Proteomics : MCP·Mathias UhlénFredrik Pontén
Jun 30, 2006·Molecular and Cellular Probes·Maria StepanovaAncha Baranova
Jan 16, 2007·Science·Sebastian J Maerkl, Stephen R Quake
Apr 6, 2007·Human Molecular Genetics·Xuting WangDouglas A Bell
Jun 15, 2007·PLoS Computational Biology·Stephen B MontgomerySteven J M Jones
Mar 14, 2009·Proceedings of the National Academy of Sciences of the United States of America·Francesco VallaniaValeria Poli

❮ Previous
Next ❯

Citations

Jun 20, 2008·Bioinformatics·Ali Torkamani, Nicholas J Schork
Dec 5, 2008·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Lingjun ZuoJoel Gelernter
Sep 22, 2009·Nucleic Acids Research·Krishna B S SwamyHuai-Kuang Tsai
Jan 23, 2010·Molecular Biology and Evolution·Gabriela G Loots, Ivan Ovcharenko
Feb 18, 2010·Genome Biology·Adam WoolfeLaura Elnitski
Mar 6, 2010·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Juan L Rodríguez-FloresDaniel T O'Connor
Sep 9, 2010·Bioinformatics·Geoff MacintyreAdam Kowalczyk
Sep 11, 2010·Genome Biology and Evolution·Kevin ChenMark L Siegal
Oct 14, 2010·Nature Reviews. Genetics·Vikas BansalNicholas J Schork
Jul 21, 2011·Physiological Genomics·Craig C BensonJoseph M Miano
Aug 4, 2011·PLoS Genetics·Stephen B MontgomeryEmmanouil T Dermitzakis
Jan 17, 2012·Briefings in Bioinformatics·Emidio CapriottiYana Bromberg
Oct 13, 2011·Genome Medicine·Rebecca Worsley-HuntWyeth W Wasserman
May 21, 2011·Bioinformatics·Guy Haskin FernaldRuss B Altman
May 12, 2009·Molekuliarnaia biologiia·V E Ramenskiĭ, Sh R Siuniaev
Nov 29, 2013·Nucleic Acids Research·Liyuan GuoJing Wang
Nov 18, 2014·Genome Medicine·Niamh M RyanKathryn L Evans
Jul 24, 2015·Nucleic Acids Research·Junbai Wang, Kirill Batmanov
Jul 29, 2011·Human Mutation·Yiqiang ZhaoSean D Mooney
Feb 20, 2013·Human Mutation·Ivan MolinerisPaolo Provero
Jul 28, 2011·Scandinavian Journal of Immunology·T Qidwai, F Khan
Mar 16, 2012·Scandinavian Journal of Immunology·T QidwaiM Y Khan
Feb 4, 2010·Human Mutation·Thomas MankeMartin Vingron
Jun 21, 2015·Bioinformatics·Chandler ZuoSündüz Keleş
Apr 25, 2016·Computational Biology and Chemistry·Rong LiRuiling Liu
Feb 1, 2015·Trends in Genetics : TIG·Anthony MathelierWyeth W Wasserman
May 2, 2013·PLoS Computational Biology·Yana Bromberg
May 23, 2016·BMC Genomics·Daniela HombachDominik Seelow
Aug 6, 2016·Nucleic Acids Research·Wenqiang ShiWyeth W Wasserman
Dec 25, 2016·Bioinformatics·Janne H KorhonenEsko Ukkonen

❮ Previous
Next ❯

Datasets Mentioned

BETA
M00146

Methods Mentioned

BETA
phylogenetic footprinting
footprinting
electrophoretic mobility

Software Mentioned

UCSC genome browser
TFBS
perl
RAVEN
Transfac
R
ORegAnno
GeneLynx
JASPAR
Bioperl

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.