胚胎重组的年龄相关变化导致精子中的染色体分离错误
Maciej J Zelazowski1, Maria Sandoval1, Lakshmi Paniker1
1Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
Cell
|September 26, 2017
概括
由于替代修复途径,年轻雄性小鼠在变质期的交叉 (CO) 重组减少. 这种低效的CO成熟可能会增加染色体错误分离的风险,并解释年轻男性的唐氏综合征发病率.
科学领域:
- 遗传学
- 细胞生物学
- 生殖生物学
背景情况:
- 分离过程中的染色体分离对于繁殖至关重要.
- 半转化需要交叉 (CO) 重组,监管机制确保每对同类染色体至少有一个CO.
研究的目的:
- 研究小雄鼠中CO衰竭的原因和后果.
- 探索年轻男性降低COs的分子机制及其与体积的潜在联系.
主要方法:
- 全基因组细胞学测试以监测重组.
- 在重组热点进行分子测试.
- 在缺乏MLH3的小鼠中进行重组的分析.
- 在人类精子细胞中评估MutLγ焦点密度.
主要成果:
- 与成年精子相比,小鼠精子显著减少COs.
- 在缺乏MLH3的年轻小鼠中,增加了涉及结构选择性核酶和替代复合物的替代途径的利用,从而导致非交叉 (NCO) 以牺牲CO为代价.
- 在年轻人精子细胞中观察到较低的MutLγ焦点密度.
结论:
- 替代修复途径的不适当活动会损害幼雄小鼠的CO成熟,可能导致染色体分离不当.
- 年轻男性的CO成熟效率降低可能导致患有唐氏综合征的孩子的风险更高.
相关概念视频
Meiosis vs. Mitosis
71.7K
Cell division is necessary for growth and reproduction in organisms. Mitosis aids cell growth and development by dividing somatic cells. In contrast, meiosis causes the division of germ cells and plays an essential role in sexual reproduction. Due to their unique functional requirements, mitosis and meiosis differ from each other in multiple aspects.
Before the start of mitosis and meiosis I, the cell synthesizes DNA, resulting in two homologous copies of each chromosome. DNA synthesis is...
Before the start of mitosis and meiosis I, the cell synthesizes DNA, resulting in two homologous copies of each chromosome. DNA synthesis is...
71.7K
Meiosis II
50.3K
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,...
50.3K
Meiosis II
209.3K
Meiosis II is the second and final stage of meiosis. It relies on the haploid cells produced during meiosis I, each of which contain only 23 chromosomes—one from each homologous initial pair. Importantly, each chromosome in these cells is composed of two joined copies, and when these cells enter meiosis II, the goal is to separate such sister chromatids using the same microtubule-based network employed in other division processes. The result of meiosis II is two haploid cells, each...
209.3K
Meiosis I
220.4K
Meiosis is a carefully orchestrated set of cell divisions, the goal of which—in humans—is to produce haploid sperm or eggs, each containing half the number of chromosomes present in somatic cells elsewhere in the body. Meiosis I is the first such division, and involves several key steps, among them: condensation of replicated chromosomes in diploid cells; the pairing of homologous chromosomes and their exchange of information; and finally, the separation of homologous chromosomes by...
220.4K
Meiosis I
45.2K
Meiosis is the division of a diploid cell into haploid cells forming sperm and eggs in animals through differentiation. Meiosis I is the first stage of meiosis, where the genetic recombination of homologous chromosomes and the reduction of the ploidy level by half occurs.
Prophase I is the most extended and complex step of meiosis I characterized by synapsis, chromosome pairing, and recombination of the homologous chromosomes. This process is facilitated by a proteinaceous structure called the...
Prophase I is the most extended and complex step of meiosis I characterized by synapsis, chromosome pairing, and recombination of the homologous chromosomes. This process is facilitated by a proteinaceous structure called the...
45.2K
Nondisjunction
82.4K
During meiosis, chromosomes occasionally separate improperly. This occurs due to failure of homologous chromosome separation during meiosis I or failed sister chromatid separation during meiosis II. In some species, notably plants, nondisjunction can result in an organism with an entire additional set of chromosomes, which is called polyploidy. In humans, nondisjunction can occur during male or female gametogenesis and the resulting gametes possess one too many or one too few chromosomes.
82.4K


