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Paul DS, Soranzo N, Beck S. Functional interpretation of non-coding sequence variation: concepts and challenges. Bioessays. 2013;36(2):191-9doi: 10.1002/bies.201300126.
Paul, D. S., Soranzo, N., & Beck, S. (2014). Functional interpretation of non-coding sequence variation: concepts and challenges. BioEssays : news and reviews in molecular, cellular and developmental biology, 36(2), 191-9. https://doi.org/10.1002/bies.201300126
Paul, Dirk S, et al. "Functional interpretation of non-coding sequence variation: concepts and challenges." BioEssays : news and reviews in molecular, cellular and developmental biology vol. 36,2 (2014): 191-9. doi: https://doi.org/10.1002/bies.201300126
Paul DS, Soranzo N, Beck S. Functional interpretation of non-coding sequence variation: concepts and challenges. Bioessays. 2014 Feb;36(2):191-9. doi: 10.1002/bies.201300126. Epub 2013 Dec 05. PMID: 24311363; PMCID: PMC3992842.
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Bioessays. 2014 Feb;36(2):191-9. doi: 10.1002/bies.201300126. Epub 2013 Dec 05.

Functional interpretation of non-coding sequence variation: concepts and challenges.

BioEssays : news and reviews in molecular, cellular and developmental biology

Dirk S Paul, Nicole Soranzo, Stephan Beck

Affiliations

  1. UCL Cancer Institute, University College London, London, United Kingdom.

PMID: 24311363 PMCID: PMC3992842 DOI: 10.1002/bies.201300126

Abstract

Understanding the functional mechanisms underlying genetic signals associated with complex traits and common diseases, such as cancer, diabetes and Alzheimer's disease, is a formidable challenge. Many genetic signals discovered through genome-wide association studies map to non-protein coding sequences, where their molecular consequences are difficult to evaluate. This article summarizes concepts for the systematic interpretation of non-coding genetic signals using genome annotation data sets in different cellular systems. We outline strategies for the global analysis of multiple association intervals and the in-depth molecular investigation of individual intervals. We highlight experimental techniques to validate candidate (potential causal) regulatory variants, with a focus on novel genome-editing techniques including CRISPR/Cas9. These approaches are also applicable to low-frequency and rare variants, which have become increasingly important in genomic studies of complex traits and diseases. There is a pressing need to translate genetic signals into biological mechanisms, leading to prognostic, diagnostic and therapeutic advances.

© 2014 The Authors. Bioessays published by WILEY Periodicals, Inc.

Keywords: GWAS; chromatin; complex traits; gene regulation; genome editing; regulatory variants

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