MOLECULAR GENETIC STUDY OF THE CRI DU CHAT SYNDROME

该项目的重点是对短臂的DNA水平分析， 人类5号染色体（5p），其重排是 与最常见的人类缺失综合征， 你好。 一个长期目标是了解分子 涉及产生染色体重排的机制 在生殖系细胞中，并确定是否以及为什么某些区域 基因组特别容易在细胞中重排 正在进行减数分裂 另一个长期目标是阐明 基因的性质和功能，参与生产 当他们被渲染时， 缺失为半合子。 这些问题正在得到解决 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的 5p的物理图，并描绘一个小区域附近的结束 5p可视为病理节段或临界节段 cri du chat的区域。 高分辨率物理和遗传图谱 将编制5p，并将提供起点， 详细克隆和分析染色体断裂点连接 并用于鉴定cri du chat关键基因中的功能基因， 地区 此外，5p的高分辨率地图将在 在解决基本问题方面， DNA含量、细胞遗传学长度和 遗传距离以及这些关系如何在不同的 染色体的长度。 分析5p的方法 而在分子水平上的猫叫综合症 一个很好的模型系统，用于深入了解复杂的遗传 疾病和解决有关染色体的基本问题 不稳定性和重排。

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.