Cohesin: role in germ cell chromosomal segregation

粘连蛋白：在生殖细胞染色体分离中的作用

• 批准号: nhmrc : 400310
• 负责人: Dr Huiling Xu
• 金额: $ 29.04万
• 依托单位: The University of Melbourne
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/cohesin-role-germ-chromosomal-segregation/76253
• 关键词: Cohesin; role; germ; cell; chromosomal

At least 10 to 25% of all human fetuses have the wrong number of chromosomes (aneuploidy). Most of these abormal fetuses perish in utero, making it the leading known cause of early pregnancy loss. Aneuploidy is the leading genetic cause of developmental disabilities and mental retardation. Abundant evidence suggests that most of these chromosome abnormalities originate during unequal partitioning of genetic material (chromosomes) in eggs and sperm. The proposed project focuses on two related genes, called Rec8 and Rad21, which we recently discovered in humans and mice. Due to that these genes are essential for chromosome separation in other species and they exists in species as diverse as yeast and humans, they may be responsible for accurate separation of chromosomes in germ cells in mammals. In this proposal, we will determine the role(s) of these molecules in controlling proper chromosome segregation by loss-of-function studies in genetically engineered mice lacking Rec8 and Rad21 genes. By analyzing the chromosomal abnormalities of the cells from these animals, we will gain critical information about the nature of chromosome partitioning disorders in humans.

至少 10% 至 25% 的人类胎儿具有错误的染色体数量（非整倍体）。大多数异常胎儿在子宫内死亡，这使其成为已知的早期流产的主要原因。非整倍体是发育障碍和智力低下的主要原因。大量证据表明，大多数染色体异常源于卵子和精子中遗传物质（染色体）的不平等分配。拟议的项目重点关注两个相关基因，即 Rec8 和 Rad21，我们最近在人类和小鼠中发现了这两个基因。由于这些基因对于其他物种的染色体分离至关重要，并且它们存在于酵母和人类等不同物种中，因此它们可能负责哺乳动物生殖细胞中染色体的准确分离。在本提案中，我们将通过缺乏 Rec8 和 Rad21 基因的基因工程小鼠的功能丧失研究来确定这些分子在控制适当染色体分离中的作用。通过分析这些动物细胞的染色体异常，我们将获得有关人类染色体分配疾病性质的重要信息。