MOLECULAR GENETIC STUDY OF THE CRI DU CHAT SYNDROME

聊天综合症的分子遗传学研究

• 批准号: 3315740
• 负责人: JOHN J WASMUTH
• 金额: $ 14.76万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3315740
• 关键词: cell transformation; chromosome disorders; cri du chat syndrome; cytogenetics; disease /disorder model; genetic disorder diagnosis; genetic library; genetic manipulation; genetic mapping; genetic markers; genetic models; genetic recombination; heterozygote; human population genetics; human tissue; hybrid cells; mental retardation; messenger RNA; molecular pathology; nucleic acid sequence

This project focuses on a DNA-level analysis of the short arm of human chromosome 5 (5p), rearrangements of which are associated with the most common human deletion syndrome, cri du chat. One long term objective is to understand the molecular mechanisms involved in generating chromosomal rearrangements in germline cells and to determine if and why certain regions of the genome are particularly susceptible to rearrangement in cells undergoing meiosis. Another long range goal is to elucidate the nature and function of genes that are involved in producing the pathologies associated with cri du chat when they are rendered hemizygous by deletion. These problems are being addressed using a combination of somatic cell genetic and recombinant DNA techniques, which have provided the means to derive an accurate physical map of 5p and to delineate a small region near the end of 5p that can be considered as the pathological segment or critical region for cri du chat. Higer resolution physical and genetic maps of 5p will be compiled and will provide the starting points for cloning and analyzing chromosome breakpoint junctions in detail and for identifying functional genes within the cri du chat critical region. Furthermore, the high resolution maps of 5p will, in themselves, be valuable in addressing basic questions concerning the relationships between DNA content, cytogenetic length and genetic distance and how the relationships can vary over the length of a chromosome. The methods in place for analyzing 5p and the cri du chat syndrome at the molecular level provide an excellent model system for gaining insight into a complex genetic disorder and for addressing basic questions related to chromosome instability and rearrangement.

该项目的重点是对短臂进行 DNA 水平分析 人类 5 号染色体 (5p)，其重排为 与最常见的人类缺失综合症相关，cri 杜聊天。 一个长期目标是了解分子 涉及产生染色体重排的机制 在生殖细胞中并确定某些区域是否以及为什么 基因组特别容易在细胞中发生重排 正在进行减数分裂。 另一个长期目标是阐明 参与产生的基因的性质和功能 渲染时与聊天叫声相关的病态 通过缺失形成半合子。 这些问题正在解决中 使用体细胞遗传和重组 DNA 的组合 技术，这些技术提供了获得准确结果的方法 5p 的物理图并在靠近末尾处划定一个小区域 5p 可以被认为是病理部分或关键部分 聊天区域。 更高分辨率的物理和遗传图谱 5p 将被编译并将提供起点 详细克隆和分析染色体断点连接 并用于识别 cri du chat 关键中的功能基因 地区。 此外，5p 的高分辨率地图将在 他们自己在解决有关的基本问题方面很有价值 DNA含量与细胞遗传学长度之间的关系 遗传距离以及关系如何随着时间的推移而变化 染色体的长度。 分析 5p 的方法 分子水平上的聊天综合症提供了一种 出色的模型系统，可深入了解复杂的遗传 紊乱并解决与染色体相关的基本问题 不稳定和重新排列。