基因组特异地图显示了在调节位点的顺序依赖性随机切换
Vitor Onuchic1,2,3,4, Eugene Lurie1,3,4, Ivenise Carrero1,3
1Molecular and Human Genetics Department, Baylor College of Medicine, Houston, TX, USA.
概括
调节性DNA的遗传变异通过改变DNA甲基化等表观遗传标记来影响健康. 这项研究绘制了这些不平衡,揭示了表观基因组变异,基因调节和疾病风险之间的联系.
科学领域:
- 基因组学
- 表观遗传学
- 人类健康
背景情况:
- 遗传变异通过调节因素影响人类健康.
- 表观遗传修饰,包括DNA甲基化和基因素标记,在基因调节中起着至关重要的作用.
- 了解遗传变异与表观遗传学之间的相互作用是解读疾病机制的关键.
研究的目的:
- 在不同的人类细胞和组织类型中创建表观遗传基失衡的高分辨率地图.
- 研究基因变异,DNA甲基化,基因组修饰和基因转录之间的关系.
- 开发一种统一的模型,将表观遗传基失衡,随机切换和与疾病相关的遗传变异联系起来.
主要方法:
- 来自13个捐赠者的36种细胞/组织类型的71个表观基因组的构建.
- 49个甲基组的深度全基因组二硫酸盐测序.
- 分析DNA甲基化,基因素标记和基因转录在异构细胞调节位点.
主要成果:
- 确定了数千个具有依赖于序列的CpG甲基化失衡的调节位点.
- 在这些位置观察到随机切换 (随机甲基化状态转换) 的丰富.
- 证明甲基化失衡是由异位基因特异性甲基化频率解释的.
- 开发了一种连接基因组不平衡,随机切换和疾病遗传学的模型.
结论:
- 在人类的调节位点中,DNA甲基化和基因素标记的依赖序列的基失衡是普遍存在的.
- 随机切换有助于基因调节部位的表观遗传变异.
- 这种表观遗传变异与人类疾病相关的遗传变异有关.
相关概念视频
Cis-regulatory Sequences
11.8K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
11.8K
Cis-regulatory Sequences
4.1K
4.1K
Multiple Allele Traits
38.1K
The Concept of Multiple Allelism
38.1K
Lethal Alleles
18.1K
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
18.1K
Switching of BJT
865
Switching behavior in Bipolar Junction Transistors (BJTs) is a fundamental aspect utilized in various electronic circuits, particularly for digital logic applications like switches and amplifiers. In a typical switching circuit, a BJT alternates between cut-off and saturation modes, corresponding to the "off" and "on" states, respectively, thus behaving like an ideal switch.
Cut-off Mode ("Off" State): In this state, both the emitter-base and collector-base junctions are...
Cut-off Mode ("Off" State): In this state, both the emitter-base and collector-base junctions are...
865
Root Loci for Positive-Feedback Systems
352
The Hartley oscillator is a positive feedback system that sustains oscillations by feeding the output back to the input in phase, thereby reinforcing the signal. Positive feedback systems can be viewed as negative feedback systems with inverted feedback signals. In these systems, the root locus encompasses all points on the s-plane where the angle of the system transfer function equals 360 degrees.
The construction rules for the root locus in positive feedback systems are similar to those in...
The construction rules for the root locus in positive feedback systems are similar to those in...
352


