A Program of Research in Population Cytogenetics

群体细胞遗传学研究计划

基本信息

批准号：
8831210
负责人：
TERRY J HASSOLD
金额：
$ 62.44万
依托单位：
WASHINGTON STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8831210
关键词：
Address Adult Affect Aneuploidy Animal Model Attention Back Caenorhabditis elegans Cell division Chromatin Chromatin Structure Chromosome Pairing Chromosome Segregation Chromosome abnormality Chromosomes Clinical Congenital Abnormality Cytogenetics DNA Sequence Data Defect Development Drosophila genus Engineering Etiology Event Failure Female Genetic Nondisjunction Genetic Recombination Germ Cells Homologous Gene Human Human Chromosomes In Vitro Infertility Lead Link Maternal Age Mechanics Meiosis Meiotic Recombination Methodology Modeling Molecular Mosaicism Mus Mutation Nature Oocytes Oogenesis Pathway interactions Pattern Population Procedures Process Prophase Research Research Personnel Role Spermatocytes Spontaneous abortion Staging Synapses System Systems Development Testing Tissues Translating Trisomy Variant Yeasts age related base egg fetal human female human male insight interest male offspring older women preference prevent programs sex sperm cell therapeutic development

项目摘要

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.

抽象的尽管母体减数分裂错误对于人类染色体异常的病因很重要，但我们对人类减数分裂过程中的染色体动态知之甚少，并且对原因如此容易出错的原因。此外，我们对特定于性别的基础几乎没有理解我们物种中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查人类卵母细胞和精子细胞中的减数分裂。通过结合与分子和定量方法论的方法，我们将回答有关减数分裂的基本问题在人类中。我们将检查并比较同源染色体找到和突触的方式在人类和男性中减数分裂预言期间，彼此之间询问突触模式如何影响跨界的形成。另外，因为在胎儿期间建立的跨界车的位置卵子发生的阶段影响成年女性的染色体分离，我们将结合获得的数据从对小鼠研究的人类研究进行测试，以解释这种关系的不同模型在重组和非分离之间。最后，我们将研究染色质结构的贡献并干扰重组率的性别差异。从这些研究获得的基本信息的临床意义是相当大的：非整倍性是我们物种流产和先天缺陷的最常见原因。了解人类减数分裂过程和性别特定差异的力学不仅提供了关键的第一步在开发预防或至少最小化错误的治疗方法中，但也关键用于开发用于在体外产生配子以治疗人类不育症的系统的信息。