小柯机器人

研究鉴定出多能细胞中罕见和常见的调节变体
2021-03-07 22:18

英国欧洲分子生物实验室Oliver Stegle等研究人员合作通过群体规模的转录组学,鉴定出多能细胞中罕见和常见的调节变体。2021年3月4日,《自然—遗传学》杂志在线发表了这一最新研究成果。

通过整合来自1,367种人类诱导多能干细胞(iPSC)系的数据,研究人员全面地绘制了人类多能细胞中常见和罕见的调节性变体图谱。使用这种群体规模的资源,研究人员发现了iPSC中数百种人类特异性的共定位事件,并鉴定出与体细胞组织相比更稀有的调节变体。最后,研究人员证明了iPSC如何能够鉴定罕见疾病的因果基因。 

据了解,iPSC是已建立的细胞系统,可在衍生的细胞类型和发育环境中研究遗传变异的影响。然而,在多能状态下,人们对遗传变异的疾病影响了解较少。

附:英文原文

Title: Identification of rare and common regulatory variants in pluripotent cells using population-scale transcriptomics

Author: Marc Jan Bonder, Craig Smail, Michael J. Gloudemans, Laure Frsard, David Jakubosky, Matteo DAntonio, Xin Li, Nicole M. Ferraro, Ivan Carcamo-Orive, Bogdan Mirauta, Daniel D. Seaton, Na Cai, Dara Vakili, Danilo Horta, Chunli Zhao, Diane B. Zastrow, Devon E. Bonner, Matthew T. Wheeler, Helena Kilpinen, Joshua W. Knowles, Erin N. Smith, Kelly A. Frazer, Stephen B. Montgomery, Oliver Stegle

Issue&Volume: 2021-03-04

Abstract: Induced pluripotent stem cells (iPSCs) are an established cellular system to study the impact of genetic variants in derived cell types and developmental contexts. However, in their pluripotent state, the disease impact of genetic variants is less well known. Here, we integrate data from 1,367 human iPSC lines to comprehensively map common and rare regulatory variants in human pluripotent cells. Using this population-scale resource, we report hundreds of new colocalization events for human traits specific to iPSCs, and find increased power to identify rare regulatory variants compared with somatic tissues. Finally, we demonstrate how iPSCs enable the identification of causal genes for rare diseases. Integrative data analysis of 1,367 human iPSC lines maps common and rare regulatory variants that colocalize with loci associated with human traits and diseases.

DOI: 10.1038/s41588-021-00800-7

Source: https://www.nature.com/articles/s41588-021-00800-7

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

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