A Program of Research in Population Cytogenetics

摘要 尽管母体减数分裂错误对人类染色体异常的病因很重要， 我们对人类女性减数分裂过程中的染色体动力学知之甚少，也对 这是为什么这个过程如此容易出错的原因。此外，我们对性别差异的基础知之甚少 我们物种减数分裂错误率或重组模式的差异。构成这一点的研究 更新应用将直接检测人类卵母细胞和精母细胞的减数分裂。通过将这一点结合起来 通过分子和定量方法，我们将回答有关减数分裂的基本问题。 在人类身上。我们将检查和比较同源染色体发现和突触的方式 在人类女性和男性减数分裂前期相互作用，并询问突触模式如何影响 跨界车的形成。此外，因为在胎儿时期建立了交叉放置 卵子发生的不同阶段会影响成年女性的染色体分离，我们将结合所获得的数据 从人体研究与小鼠实验不同的模型提出解释关系 在重组和不析取之间。最后，我们将研究染色质结构的贡献 以及对重组率性别差异的干扰。 从这些研究中获得的基本信息具有相当大的临床意义： 非整倍体是人类流产和出生缺陷的最常见原因。了解 人类减数分裂过程的机制和性别差异不仅提供了至关重要的第一步 在开发治疗方法以防止或至少最大限度地减少错误方面，但也至关重要 开发体外产生配子治疗人类不育症的系统的信息。

ABSTRACT Despite the importance of maternal meiotic errors to the etiology of human chromosome abnormalities, we know very little about chromosome dynamics during human female meiosis, and remain ignorant of the reasons why the process is so error-prone. Further, we have little understanding of the basis of the sex-specific differences in meiotic error rate or recombination patterns in our species. The studies that comprise this renewal application will directly examine meiosis in human oocytes and spermatocytes. By combining this approach with molecular and quantitative methodologies, we will answer fundamental questions about meiosis in humans. We will examine and compare the way in which homologous chromosomes find and synapse with one another during meiotic prophase in the human female and male and ask how synaptic patterns influence the formation of crossovers. In addition, because the placement of crossovers established during the fetal stages of oogenesis affects chromosome segregation in the adult female, we will combine the data obtained from human studies with studies in the mouse to test different models proposed to explain the relationship between recombination and nondisjunction. Finally, we will examine the contribution of chromatin structure and interference to sex-specific differences in recombination rates. The clinical implications of the basic information obtained from these studies are considerable: Aneuploidy is the most common cause of miscarriage and birth defects in our species. Understanding the mechanics of the meiotic process in humans and sex-specific differences not only provides a crucial first step in the development of therapeutic approaches to prevent or at least minimize errors, but also critical information for the development of systems for producing gametes in vitro to treat human infertility.