Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK.
J Intern Med. 2012 Apr;271(4):379-91. doi: 10.1111/j.1365-2796.2011.02508.x.
The individual human genome and epigenome are being defined at unprecedented resolution by current advances in sequencing technologies with important implications for human disease. This review uses examples relevant to clinical practice to illustrate the functional consequences of genetic and epigenetic variation. The insights gained from genome-wide association studies are described together with current efforts to understand the role of rare variants in common disease, set in the context of recent successes in Mendelian traits through the application of whole exome sequencing. The application of functional genomics to interrogate the genome and epigenome, build up an integrated picture of the regulatory genomic landscape and inform disease association studies is discussed, together with the role of expression quantitative trait mapping and analysis of allele-specific gene expression.
当前测序技术的进步正在以前所未有的分辨率定义个体人类基因组和表观基因组，这对人类疾病具有重要意义。本综述使用与临床实践相关的例子来说明遗传和表观遗传变异的功能后果。描述了全基因组关联研究的结果，以及目前努力理解常见疾病中罕见变异的作用，这是在通过应用外显子组测序成功解决孟德尔性状的背景下进行的。讨论了应用功能基因组学来研究基因组和表观基因组，构建调控基因组景观的综合图像，并为疾病关联研究提供信息，以及表达数量性状映射和等位基因特异性基因表达分析的作用。
