title: Identification of altered cis-regulatory elements in human disease.
abstract: It has long been appreciated that variations in regulatory regions of genes can impact gene expression. With the advent of whole-genome sequencing (WGS), it has become possible to begin cataloging these noncoding variants. Evidence continues to accumulate linking clinical cases with cis-regulatory element disruption in a wide range of diseases. Identifying variants is becoming routine, but assessing their impact on regulation remains challenging. Bioinformatics approaches that identify variations functionally altering transcription factor (TF) binding are increasingly important for meeting this challenge. We present the current state of computational tools and resources for identifying the genomic regulatory components (cis-regulatory regions and TF binding sites, TFBSs) controlling gene transcriptional regulation. We review how such approaches can be used to interpret the potential disease causality of point mutations and small insertions or deletions. We hope this will motivate further the development of methods enabling the identification of etiological cis-regulatory variations.
authors: Centre for Molecular Medicine and Therapeutics, 950 West 28th Avenue, Vancouver, BC V5Z 4H4, Canada.
authors: Anthony
authors: A
authors: Mathelier
authors: Centre for Molecular Medicine and Therapeutics, 950 West 28th Avenue, Vancouver, BC V5Z 4H4, Canada.
authors: Wenqiang
authors: W
authors: Shi
authors: Centre for Molecular Medicine and Therapeutics, 950 West 28th Avenue, Vancouver, BC V5Z 4H4, Canada. Electronic address: wyeth@cmmt.ubc.ca.
authors: Wyeth W
authors: WW
authors: Wasserman
mesh_terms: D001665:Binding Sites; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human; D023281:Genomics / Q000379:methods; D006801:Humans; D011485:Protein Binding; D050436:Regulatory Elements, Transcriptional; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors
keywords: ChIP-seq; cis-regulatory elements; noncoding variants; personalized medicine; transcription factor binding sites (TFBSs); whole-genome sequencing (WGS)