研究揭示短串联重复序列对基因表达的影响
2019-11-03 00:01
美国加州大学旧金山分校Melissa Gymrek等研究人员系统性揭示了短串联重复序列（STR）变异对基因表达的影响。相关论文11月1日在线发表于《自然—遗传学》。
研究人员利用来自基因型组织表达计划的17个组织的全基因组测序和表达数据，鉴定出28000个STR，其重复数与附近基因（eSTR）的表达有关。研究人员使用了精细映射来量化每个eSTR因果关系的可能性，并表征前1400个精细映射的eSTR。研究人员确定了数百种与已发表的全基因组关联研究信号相关的eSTR，并将特定的eSTR关联到复杂的性状中，包括身高、精神分裂症、炎症性肠病和智力。总体而言，这些结果支持以下假设：eSTR贡献于大量的人类表型；并且这些数据可作为以后研究复杂性状的宝贵资源。
据介绍，STR与人类的各种复杂性状有关。但迄今为止，STR对基因表达影响的全基因组相关研究对于检测关联性并对潜在机制提供见解的能力有限。
附：英文原文
Title:The impact of short tandem repeat variation on gene expression
Author:Stephanie Feupe Fotsing, Jonathan Margoliash, Catherine Wang, Shubham Saini, Richard Yanicky, Sharona Shleizer-Burko, Alon Goren & Melissa Gymrek
Issue&Volume:01 November 2019
Abstract: Short tandem repeats (STRs) have been implicated in a variety of complex traits in humans. However, genome-wide studies of the effects of STRs on gene expression thus far have had limited power to detect associations and provide insights into putative mechanisms. Here, we leverage whole-genome sequencing and expression data for 17 tissues from the Genotype–Tissue Expression Project to identify more than 28,000 STRs for which repeat number is associated with expression of nearby genes (eSTRs). We use fine-mapping to quantify the probability that each eSTR is causal and characterize the top 1,400 fine-mapped eSTRs. We identify hundreds of eSTRs linked with published genome-wide association study signals and implicate specific eSTRs in complex traits, including height, schizophrenia, inflammatory bowel disease and intelligence. Overall, our results support the hypothesis that eSTRs contribute to a range of human phenotypes, and our data should serve as a valuable resource for future studies of complex traits.
DOI:10.1038/s41588-019-0521-9
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：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex
本期文章：《自然—遗传学》：Online/在线发表
