Meiotic recombination in human oocytes.
Meiotic recombination in human oocytes.
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DOI：
10.1371/journal.pgen.1000661
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发表时间：
2009-09
期刊：
影响因子：
4.5
通讯作者：
Hassold TJ
中科院分区：
文献类型：
--
作者：
Cheng EY;Hunt PA;Naluai-Cecchini TA;Fligner CL;Fujimoto VY;Pasternack TL;Schwartz JM;Steinauer JE;Woodruff TJ;Cherry SM;Hansen TA;Vallente RU;Broman KW;Hassold TJ
对人类三体的研究表明异常减数分裂重组与随后的母体减数分裂I或II不分离之间存在显著的关系。具体地，重组失败或重组事件位于太靠近或太远离着丝粒已被链接到人类三体的起源。利用免疫荧光方法直接检测人类女性减数分裂重组过程，应该可以鉴定这些异常的交换构型。因此，我们开始了交叉相关蛋白质的研究（例如，MLH1）在人类胎儿卵母细胞中的表达，以分析它们在非分离倾向人类染色体上的数量和分布，更一般地，以表征人类女性中全基因组重组水平。我们的分析表明，MLH1病灶的数量低于预测的遗传连锁分析，但其定位模式符合预期的交叉相关蛋白。在个别染色体的研究中，我们的观察提供了证据，在胎儿卵母细胞中存在“脆弱”的交叉配置，与这些随后被翻译成在成年卵母细胞中的非分离事件的想法一致。在卵子和精子形成的过程中，一个决定性的事件是减数分裂重组，这是一个DNA在“伴侣”染色体之间交换的过程。如果这一过程受到干扰，染色体往往会在减数分裂过程中误入歧途，导致卵子或精子染色体过多或过少。在人类中，产生的胚胎几乎总是异常的，并且是流产或先天性出生缺陷的主要来源（例如，唐氏综合征）。在过去的十年中，技术已经成为可能的检查减数分裂重组“，因为它发生”在人类卵子，这使我们能够定义这个过程的属性。在本研究中，我们使用这种方法来描述人类胎儿卵母细胞减数分裂重组，并询问我们是否可以识别异常重组模式。的确，我们在研究的每条染色体上都观察到了这样的模式，尽管在单个染色体中观察到了不同的异常。因此，出生前的因素影响成年卵母细胞中染色体错误分裂的可能性，尽管那些使21号染色体错误分裂（导致唐氏综合症）的因素可能与那些使其他染色体错误分裂的因素不同。
Studies of human trisomies indicate a remarkable relationship between abnormal meiotic recombination and subsequent nondisjunction at maternal meiosis I or II. Specifically, failure to recombine or recombination events located either too near to or too far from the centromere have been linked to the origin of human trisomies. It should be possible to identify these abnormal crossover configurations by using immunofluorescence methodology to directly examine the meiotic recombination process in the human female. Accordingly, we initiated studies of crossover-associated proteins (e.g., MLH1) in human fetal oocytes to analyze their number and distribution on nondisjunction-prone human chromosomes and, more generally, to characterize genome-wide levels of recombination in the human female. Our analyses indicate that the number of MLH1 foci is lower than predicted from genetic linkage analysis, but its localization pattern conforms to that expected for a crossover-associated protein. In studies of individual chromosomes, our observations provide evidence for the presence of “vulnerable” crossover configurations in the fetal oocyte, consistent with the idea that these are subsequently translated into nondisjunctional events in the adult oocyte. One of the defining events in the formation of eggs and sperm is meiotic recombination, a process in which DNA is exchanged between “partner” chromosomes. If this process is perturbed, chromosomes often go astray during meiotic division, resulting in eggs or sperm with too many or too few chromosomes. In humans, the resulting embryos are almost always abnormal and are a major source of miscarriages or congenital birth defects (e.g., Down syndrome). Over the past decade, techniques have become available that make possible the examination of meiotic recombination “as it happens” in the human egg, and this has allowed us to define the properties of this process. In the present study, we used this methodology to characterize meiotic recombination in human fetal oocytes and to ask whether we could identify abnormal recombination patterns. Such patterns were, indeed, observed for each chromosome we studied, although different abnormalities were observed among the individual chromosomes. Thus, factors operating before birth influence the likelihood of chromosome misdivision in the adult oocyte, although those that make chromosome 21 misdivide (leading to Down syndrome) may not be the same as those that make other chromosomes misdivide.
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影响因子：
4.5
作者：
Holloway JK;Booth J;Edelmann W;McGowan CH;Cohen PE
通讯作者：
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