MOLECULAR GENETIC STUDY OF THE CRI DU CHAT SYNDROME

这个项目主要是对短臂的DNA水平进行分析 人类5号染色体(5p)，其重排是 与最常见的人类缺失综合症CRI有关 多聊一聊。一个长期的目标是理解分子 产生染色体重排的机制 在生殖系细胞中，并确定是否以及为什么 基因组特别容易在细胞内重排 正在进行减数分裂的另一个长期目标是阐明 参与生产的基因的性质和功能 渲染时与cri du chat相关的病理 被删除的半合子。这些问题正在得到解决 利用体细胞遗传和重组DNA的组合 技术，这些技术提供了一种方法来得出准确的 5P的物理地图，并在接近尾声的地方勾画出一个小区域 可视为病变节段或危重的5P CRI DU聊天的区域。更高分辨率的物理和遗传图谱 将被汇编，并将提供以下起点 染色体断点连接的详细克隆和分析 并用于识别关键的cri du chat内的功能基因 区域。此外，5P的高分辨率地图将在 在解决有关以下方面的基本问题方面具有价值 DNA含量、细胞遗传长度与DNA含量的关系 遗传距离以及这些关系在不同时期的变化 染色体的长度。现有的分析5P的方法 而分子水平上的CRI DU Chat综合征提供了一种 用于洞察复杂基因的优秀模型系统 用于解决与染色体有关的基本问题 不稳定和重排。

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.