在CIP2A变体中,功能丧失与早期胚胎停产和碎片化的女性不孕症有关
Zhenxing Liu1, Qingsong Xi2, Meiqi Hou1
1Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
概括
一种新的CIP2A基因变异导致早期胚胎停产和分裂 (EEAF),这是一个常见的不孕症因素. 这种功能丧失突变会损害人类卵细胞和早期胚胎发育,突出显示CIP2A.
科学领域:
- 生殖生物学 生殖生物学
- 遗传学 遗传学 是一个
- 细胞生物学 细胞生物学
背景情况:
- 早期胚胎停止和碎片化 (EEAF) 是女性不孕症的重要原因,其遗传基础基本上尚不清楚.
- CIP2A是PP2A的细胞抑制剂,对小鼠卵细胞中的线粒分裂和半分裂至关重要.
研究的目的:
- 为了确定血缘家族中EEAF的遗传原因.
- 阐明CIP2A在人类卵细胞和早期胚胎发育中的作用.
主要方法:
- 埃克索姆和桑格测序被用来识别致病基因.
- 对CIP2A变异的功能验证在细胞系和人类卵子细胞中进行,使用西式斑点,RT-PCR,TUNEL染色和光局部化.
- 患者的表型被CIP2A knockdown在人类卵细胞中复制.
主要成果:
- 在CIP2A (c.1510C>T,p.L504F) 中,一种新的功能丧失变异被确定为人类EEAF的原因.
- 这种CIP2A变异导致蛋白质表达减少,蛋白质聚合异常和细胞亡.
- 在患者卵细胞和胚胎中观察到异常的CIP2A聚合和染色体分散,酸化ERK1/2水平降低.
结论:
- 该研究确定CIP2A是EEAF特征的女性不孕症的新型致病基因.
- 在CIP2A中功能丧失的变体破坏了人类卵细胞和早期胚胎发育.
- CIP2A在早期人类生殖过程中发挥着独特而至关重要的作用.
更多相关视频
08:22A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations
Published on: December 1, 2017
8.6K
09:37Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information
Published on: August 15, 2019
9.7K
相关概念视频
02:30Genomic Imprinting and Inheritance
34.3K
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...
34.3K
02:02Meiosis II
45.6K
Meiosis II entails cell division and segregation of the sister chromatids, resulting in the production of four unique haploid gametes. The steps for meiosis II are similar to mitosis, except that meiosis II occurs in haploid cells, whereas mitosis occurs in diploid cells.
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
45.6K
01:43Sex-linked Disorders
102.0K
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
102.0K
02:57piRNA - Piwi-interacting RNAs
6.8K
PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
6.8K
02:20Cohesins
4.5K
Cohesin protein complexes are a molecular glue that holds two sister chromatids together. They play an important role both in mitosis and meiosis. In mitosis, all cohesin complexes present on the chromosomes are removed before the start of the anaphase stage.
Cohesin complexes in Meiotic Division
Meiosis involves two distinct rounds of chromosomal segregation and cell divisions— Meiosis I followed by Meiosis II – producing four daughter cells. Meiosis I includes the separation of...
Cohesin complexes in Meiotic Division
Meiosis involves two distinct rounds of chromosomal segregation and cell divisions— Meiosis I followed by Meiosis II – producing four daughter cells. Meiosis I includes the separation of...
4.5K
01:21Nondisjunction
3.8K
Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate correctly and move to the opposite poles of the cells. This produces daughter cells with abnormal chromosome numbers. Nondisjunction is common during anaphase I or anaphase II of meiosis. Mutations in synaptonemal complex proteins that attach homologous chromosomes increase the chances of nondisjunction in anaphase I of meiosis I. In contrast, mutations in topoisomerases and condensins that hold...
3.8K