Future impact of integrated high-throughput methylome analyses on human health and disease

作     者：Lee M Butcher Stephan Beck 

作者机构：UCL Cancer Institute Paul O'Gorman Building University College London 72 Huntley Street London WC1E 6BT UK 

出 版 物：《Journal of Genetics and Genomics》 (遗传学报（英文版）)

年 卷 期：2008年第35卷第7期

页      面：391-401页

核心收录：

学科分类：0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 07[理学] 071007[理学-遗传学] 

基　　金：Wellcome Trust WT 

主　　题：DNA methylation reverse phenotyping complex disease 

摘      要：A spate of high-powered genome-wide association studies （GWAS） have recently identified numerous single-nucleotide polymorphisms （SNPs） robustly linked with complex disease. Despite interrogating the majority of common human variation, these SNPs only account for a small proportion of the phenotypic variance, which suggests genetic factors are acting in concert with non-genetic factors. Although environmental measures are logical covariants for genotype-phenotype investigations, another non-genetic intermediary exists： epigenetics. Epigenetics is the analysis of somatically-acquired and, in some cases, transgenerationally inherited epigenetic modifications that regulate gene expression, and offers to bridge the gap between genetics and environment to understand phenotype. The most widely studied epigenetic mark is DNA methylation. Aberrant methylation at gene promoters is strongly implicated in disease etiology, most notably cancer. This review will highlight the importance of DNA methylation as an epigenetic regulator, outline techniques to characterize the DNA methylome and present the idea of reverse phenotyping, where multiple layers of analysis are integrated at the individual level to create personalized digital phenotypes and, at a phenotype level, to identify novel molecular signatures of disease.