全基因组增强器图将风险变异与疾病基因联系起来
Joseph Nasser1, Drew T Bergman1, Charles P Fulco1,2
1Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nature
|April 8, 2021
概括
这项研究绘制了131种人类细胞类型的基因增强剂,将数千个全基因组关联研究 (GWAS) 信号与特定的基因联系起来,并揭示了疾病机制. 这些发现有助于解释常见疾病的遗传风险变异.
科学领域:
- 基因组学
- 分子生物学
- 系统生物学
背景情况:
- 全基因组关联研究 (GWAS) 识别了许多与人类疾病和复杂特征相关的非编码基因位置.
- 由于缺乏基因增强剂及其向基因的准确地图,解释这些GWAS发现具有挑战性.
研究的目的:
- 在131种人类细胞类型和组织中创建全面的增强基因地图.
- 使用这些地图来解释GWAS识别的变体的功能.
- 确定常见疾病的基因和调控机制.
主要方法:
- 使用活动-接触 (ABC) 模型来预测增强剂-基因相互作用.
- 在131种不同类型的人类细胞和组织中生成增强基因图.
- 这些地图与72种疾病和复杂特征的GWAS数据的整合.
主要成果:
- 该ABC模型将5036个GWAS信号与72个疾病中的2249个基因联系起来.
- 通过作用于不同细胞类型的增强剂,确定了577个影响多个表型的基因.
- 与其他方法相比,预测增强剂 (例如树突细胞) 的炎症性肠病 (IBD) 致病变体显著增强,精度更高.
- 发现了一种特定的增强剂-IBD风险变异链接,调节PPIF表达以影响巨细胞中的线粒体膜潜力.
结论:
- 这项研究为将非编码风险变体与它们的分子和细胞功能联系起来提供了宝贵的资源和可通用的策略.
- 揭示了基因组调节的基本原则,并确定了参与IBD病变的关键基因.
- 能够更深入地了解常见疾病的遗传结构.
相关概念视频
01:11Genome-wide Association Studies-GWAS
14.9K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
14.9K
01:05Single Nucleotide Polymorphisms-SNPs
17.2K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
17.2K
02:46Genetic Screens
5.3K
Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
5.3K