一种自然存在的MBD4变体在灵长类动物中引起母胚生殖系突变
Alexandra M Stendahl1, Rashesh Sanghvi2, Samuel Peterson1
1Division of Genetics, Oregon National Primate Research Center, Beaverton, Oregon 97006, USA.
Genome research
|November 20, 2023
概括
甲基-CpG结合域4的罕见突变,DNA糖化酶 (MBD4) 基因导致 rhesus 子后代的生殖线突变. 这项研究揭示了MBD4
科学领域:
- 遗传学 遗传学 是一个
- 基因组学就是基因组学.
- 分子生物学分子生物学
背景情况:
- 甲基-CpG结合域4的DNA糖解酶 (MBD4) 基因对于修复C>T脱胺突变在CpG部位至关重要.
- MBD4功能障碍与人类体质突变和癌症倾向有关.
研究的目的:
- 为了研究生殖线MBD4框架转移突变对 rhesus子后代de novo突变率的影响.
- 探索MBD4在CpG二核酸之外的生殖系突变修复中的作用.
主要方法:
- 一个 rhesus 家族的基因组测序,具有 homozygous MBD4 框架转移突变.
- 对MBD4-null后代的新突变负担和类型的分析.
主要成果:
- 在MBD4-null大的后代中,新突变负担增加了四到六倍.
- 过多的突变主要是C>T在CpG位点,与MBD4功能丧失一致.
- 在CpA位点观察到C>T突变的显著过量,这表明MBD4在这些环境中没有被重视的作用.
结论:
- 这项研究提供了第一个遗传因素导致哺乳动物生殖线突变的证据.
- MBD4在修复母体生殖系中CpG和CpA位点的DNA除中发挥着重要作用.
- 自然发生的调节生殖系突变率的变异很少见,MBD4功能丧失是值得注意的例子.
相关概念视频
Mismatch Repair
4.9K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
4.9K
Animal Mitochondrial Genetics
7.6K
Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
7.6K
Mutations
83.1K
Overview
83.1K
Exon Recombination
3.6K
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon...
Exon shuffling follows “splice frame rules.” Each exon...
3.6K
Genomic Imprinting and Inheritance
34.6K
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...
34.6K
Genome Copying Errors
4.2K
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.
4.2K


