人类发育中的基因,异形和拼接调节的交叉祖先图谱
Cindy Wen1,2,3, Michael Margolis2,3, Rujia Dai4
1Interdepartmental Program in Bioinformatics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
概括
这项研究绘制了人类大脑发育的调节元素, 以确定与自闭症和精神分裂症等神经精神疾病相关的基因. 它揭示了异形调节
科学领域:
- 神经科学
- 遗传学
- 发育生物学
背景情况:
- 神经精神病学全基因组关联研究 (GWAS) 显示,发育中的大脑中调节元素的丰富.
- 没有一个统一的脑发育监管图谱,
研究的目的:
- 创建一个关于人类大脑发育的综合性监管图谱.
- 识别和优先考虑神经精神疾病的基因和调控机制.
主要方法:
- 在672个发育中的人类大脑中分析了基因,异型和拼接定量特征位点 (QTL).
- 将QTL映射到特定的细胞环境中,并分析基因表达的遗传性.
- 使用协同表达网络来优先考虑GWAS位置和上下文发现的机制.
主要成果:
- 确定了15752个具有调节性QTL的基因,将3739个映射到细胞环境中.
- 在发育过程中观察到基因表达遗传性的下降,与细胞异质性和神经元成熟有关.
- 异形水平调节,特别是在妊娠的第二个三个月,对GWAS遗传性有显著的贡献.
- 在五种疾病中约有60%的GWAS位点的优先机制,优于成年人大脑研究.
结论:
- 对于理解神经精神疾病至关重要.
- 在大脑发育过程中,异形调节在调节遗传风险方面发挥着关键作用.
- 这本地图书提供了转录组调节在发育和疾病的综合景观.
相关概念视频
Human Genetics
559
Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
The complex relationship between genetics and psychology is observable through common biological components such...
559
Regulation of Expression at Multiple Steps
892
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
892
DNA Microarrays
17.3K
Microarrays are high-throughput and relatively inexpensive assays that can be automated to analyze large quantities of data at a time. They are used in genome-wide studies to compare gene or protein expression under two varied conditions, such as healthy and diseased states. Microarrays consist of glass or silica slides on which probe molecules are covalently attached through surface functionalization. Most commonly, the slides are prepared through the chemisorption of silanes to silica...
17.3K
Chromatin Structure and RNA Splicing
2.7K
2.7K
Regulation of Expression Occurs at Multiple Steps
22.6K
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
22.6K


