MORC2的性作用源于其表观遗传特征
Fatemeh Peymani1,2, Tomohiro Ebihara2, Dmitrii Smirnov1,2
1Institute of Human Genetics, School of Medicine and Health, Technical University of Munich, 81675 Munich, Germany.
Brain : a journal of neurology
|April 30, 2025
概括
在MORC2的致病变体导致DNA甲基化签名,导致基因抑制和患者的各种症状. 这种表观遗传变化解释了MORC2相关疾病的不同临床结果.
科学领域:
- 遗传学 遗传学 是一个
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 在MORC2中异构错义突变与各种临床条件有关,从早期神经发育问题到晚期发作的神经病变.
- 对于MORC2突变的广泛症状和类效应的潜在机制尚不清楚.
研究的目的:
- 研究MORC2相关疾病中表型异质性背后的分子机制.
- 为了确定一种潜在的表观遗传联系,解释MORC2突变的类效应.
主要方法:
- 对53名MORC2突变患者的DNA甲基化,转录体,蛋白质体和临床表型的分析.
- 利用多omics数据将分子变化与临床表现相关联.
主要成果:
- 在所有表型和组织中确定了一个通用的MORC2特异性DNA甲基化表征.
- 在促进子区域观察到DNA高甲基化,导致转录抑制和独特的RNA签名.
- 低调ERCC8,NDUFAF2和FKTN与特定的临床特征相关联,如利氏综合征和异形特征.
结论:
- 致病性MORC2变体诱导特定的DNA甲基化特征,解释了类型和表型异质性.
- 表观遗传变异,特别是DNA甲基化变化,被认为是MORC2疾病和潜在的其他孟德尔条件中的类变异的关键机制.
更多相关视频
09:37Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information
Published on: August 15, 2019
9.6K
09:34Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
33.4K
相关概念视频
Master Transcription Regulators
6.7K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.7K
Pleiotropy
37.8K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
37.8K
Epigenetic Regulation
2.9K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
2.9K
Genomic Imprinting and Inheritance
32.8K
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
32.8K
Position-effect Variegation
6.2K
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
6.2K
Epistasis
43.4K
In addition to multiple alleles at the same locus influencing traits, numerous genes or alleles at different locations may interact and influence phenotypes in a phenomenon called epistasis. For example, rabbit fur can be black or brown depending on whether the animal is homozygous dominant or heterozygous at a TYRP1 locus. However, if the rabbit is also homozygous recessive at a locus on the tyrosinase gene (TYR), it will have an unshaded coat that appears white, regardless of its TYRP1...
43.4K
