Genome-wide assays that identify and quantify modified cytosines in human disease studies

Netha Ulahannan, John M. Greally

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The number of different assays that has been published to study DNA methylation is extensive, complemented by recently described assays that test modifications of cytosine other than the most abundant 5-methylcytosine (5mC) variant. In this review, we describe the considerations involved in choosing how to study 5mC throughout the genome, with an emphasis on the common application of testing for epigenetic dysregulation in human disease. While microarray studies of 5mC continue to be commonly used, these lack the additional qualitative information from sequencing-based approaches that is increasingly recognized to be valuable. When we test the representation of functional elements in the human genome by several current assay types, we find that no survey approach interrogates anything more than a small minority of the nonpromoter cis-regulatory sites where DNA methylation variability is now appreciated to influence gene expression and to be associated with human disease. However, whole-genome bisulphite sequencing (WGBS) adds a substantial representation of loci at which DNA methylation changes are unlikely to be occurring with transcriptional consequences. Our assessment is that the most effective approach to DNA methylation studies in human diseases is to use targeted bisulphite sequencing of the cis-regulatory loci in a cell type of interest, using a capture-based or comparable system, and that no single design of a survey approach will be suitable for all cell types.

Original languageEnglish (US)
Pages (from-to)1-14
Number of pages14
JournalEpigenetics and Chromatin
DOIs
StateAccepted/In press - Jan 22 2015

Fingerprint

Cytosine
DNA Methylation
5-Methylcytosine
Genome
Human Genome
Epigenomics
Gene Expression
Surveys and Questionnaires

Keywords

  • 5-methylcytosine
  • Assay
  • CpG island
  • DNA methylation
  • Enhancer
  • Epigenomic
  • microarray

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology

Cite this

Genome-wide assays that identify and quantify modified cytosines in human disease studies. / Ulahannan, Netha; Greally, John M.

In: Epigenetics and Chromatin, 22.01.2015, p. 1-14.

Research output: Contribution to journalArticle

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