染色体不稳定和免疫缺陷综合征是由DNA甲基转移酶基因突变引起的
G L Xu1, T H Bestor, D Bourc'his
1Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, New York 10032, USA.
Nature
|January 26, 2000
概括
免疫缺陷,中粒体不稳定和面部异常 (ICF) 综合征与DNA甲基转移酶3B的突变有关. 这种遗传性疾病破坏了基因组甲基化模式,影响了染色体的稳定性和免疫功能.
科学领域:
- 遗传学 是一个遗传学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 人类疾病 人类疾病
背景情况:
- ICF综合征是一种罕见的自体相衰退性疾病,其特点是免疫缺陷,中粒体不稳定性和面部异常.
- 患者经常经历严重的感染,并在成年之前因免疫球蛋白水平降低而死亡.
- 细胞遗传异常包括异性染色体延长,多辐射染色体和异常的核结构.
研究的目的:
- 为了研究ICF综合征的遗传基础.
- 为了确定负责观察到的甲基化缺陷和临床特征的特定基因突变.
- 了解DNA甲基化在维持基因组稳定性和免疫功能中的作用.
主要方法:
- 对五名与ICF无关的患者进行基因分析.
- 对DNA甲基转移酶3B (DNMT3B) 基因的突变查.
- 对患者组织中的基因组甲基化模式的分析.
主要成果:
- 发现五名ICF患者在DNMT3B基因的两个等位基因中都有突变.
- ICF综合征与卫星DNA中几乎完全缺乏细胞因子甲基化有关.
- DNMT3B突变破坏了异染色体组织和基因组甲基化模式.
结论:
- 在DNMT3B基因的突变是ICF综合征的原因.
- 通过DNMT3B进行适当的细胞因子甲基化对于基因组稳定性和正常的免疫功能至关重要.
- ICF综合征代表了一种独特的遗传疾病,影响了构成性基因组甲基化.
相关概念视频
01:08Nucleotide Excision Repair
Overview
01:39Mutations
Overview
02:46Genome Copying Errors
DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their survival. Therefore, the copying errors are checked and repaired at three levels.
01:35Mutations
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
01:38Nucleotide Excision Repair
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
01:30Spontaneous and Induced Mutations
Spontaneous mutations arise infrequently during DNA replication due to errors in the process. A key factor behind these errors is tautomeric shifts in nitrogenous bases, where bases transition from keto to enol forms or amino to imino forms. This shift can alter base-pairing rules, leading to mutations. Additionally, reactive oxygen species (ROS) arising from aerobic metabolism can damage DNA, resulting in depurination (loss of a purine base) or depyrimidination (loss of a pyrimidine base).