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科学家提出高通量鉴定人单核苷酸多态性
作者:小柯机器人 发布时间:2019/7/27 10:16:59

荷兰癌症研究所Bas van Steensel团队取得一项新突破。他们的最新研究提出了用高通量的方法调查和鉴定影响调控元件活性的人类单核苷酸多态性。 该研究于2019年7月发表于国际学术期刊《自然—遗传学》上。

研究组利用高通量和高分辨率的调控元件调查(SuRE)报告技术来调查590万个SNPs(包括57%的已知常见SNPs)对增强子和启动子活性的影响。研究确定了有超过30,000个SNP可以影响一些假定的调控元件的活性,并且部分以细胞类型特异性的方式影响调控元件的活性。将这一数据集与GWAS结果相结合,可能有助于查明SNP在影响人类特征方面的作用。

据了解,人类基因组中数以百万计的snp中,大多数是非编码的,而且许多与假定的调控元件重叠。全基因组关联研究(GWAS)已将许多snp与人类特征或基因表达水平联系起来,但很少有足够的分辨率来鉴定出有因果关系的SNP。以前,基于报告实验的功能性筛选的通量很小,不足以测试如此大量的SNP对调控元件活性的可能影响。

附:英文原文

Title: High-throughput identification of human SNPs affecting regulatory element activity

Author: Joris van Arensbergen, Ludo Pagie, Vincent D. FitzPatrick, Marcel de Haas, Marijke P. Baltissen, Federico Comoglio, Robin H. van der Weide, Hans Teunissen, Urmo Vsa, Lude Franke, Elzo de Wit, Michiel Vermeulen, Harmen J. Bussemaker, Bas van Steensel

Issue&Volume: Volume 51 Issue 7, July 2019

Abstract: Most of the millions of SNPs in the human genome are non-coding, and many overlap with putative regulatory elements. Genome-wide association studies (GWAS) have linked many of these SNPs to human traits or to gene expression levels, but rarely with sufficient resolution to identify the causal SNPs. Functional screens based on reporter assays have previously been of insufficient throughput to test the vast space of SNPs for possible effects on regulatory element activity. Here we leveraged the throughput and resolution of the survey of regulatory elements (SuRE) reporter technology to survey the effect of 5.9 million SNPs, including 57% of the known common SNPs, on enhancer and promoter activity. We identified more than 30,000 SNPs that alter the activity of putative regulatory elements, partially in a cell-type-specific manner. Integration of this dataset with GWAS results may help to pinpoint SNPs that underlie human traits.

DOI: 10.1038/s41588-019-0455-2

Source: https://www.nature.com/articles/s41588-019-0455-2

期刊信息

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:25.455
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex