MOLECULAR GENETIC STUDY OF THE CRI DU CHAT SYNDROME

该研究项目的目的是在分子水平上研究， 已知最常见的人类删除综合症，cri du chat。 这些研究 将包括使用重组 DNA 探针定义上的精确区域 5 号染色体的短臂，删除后负责 产生“cri du chat”的临床和表型症状 综合症。 一旦在 DNA 水平上定义了这样的区域，我们将尝试 鉴定产物（RNA转录物和/或其多肽 翻译产物）定位于该表型的基因 5号染色体短臂的相关片段。此外，在各种 患有“聊天综合症”的人，其中删除的染色体已 从头开始，我们将确定删除的染色体是否是 父亲或母亲的血统。 目前还无法执行 针对任何人类缺失综合症的此类分析。 项目 利用体细胞遗传和重组 DNA 的组合 技术。 我们为研究这种疾病而建立的系统 使我们能够在种间体细胞杂交中分离出改变的 5 号染色体的衍生物，来自具有该染色体各种缺失的人 染色体。 这使我们能够研究改变的 5 号染色体和 DNA 除了正常的 5 号染色体同源物之外，还删除了它们的序列 存在于这些人的细胞中。 此外，我们还有一个重组体 人类染色体短臂特异的基因组 DNA 文库 5，这将使我们能够识别和定位独特的DNA序列 人类基因组这部分的特定区域，包括 与产生“尖叫综合症”的症状有关 已删除。 该系统提供了获得财富的独特机会 有关最常见的人类缺失综合症的信息并研究 复杂的生物和医学问题达到了前所未有的水平 已经成为可能。

The purpose of this research project is to study, at the molecular level, the most common human deletion syndrome known, cri du chat. These studies will include defining, using recombinant DNA probes, the precise region on the short arm of chromosome 5 that is responsible, when deleted, for producing the clinical and phenotypic symptoms of the cri du chat syndrome. Once such a region is defined at the DNA level, we will attempt to identify the products (RNA transcripts and/or their polypeptide translation products) of the genes localized to this phenotypically relevant segment of the short arm of chromosome 5. In addition, in various persons with cri du chat syndrome in which the deleted chromosome has arisen de novo, we will determine whether the deleted chromosome is of paternal or maternal origin. At present, it is not possible to perform these kinds of analyses for any human deletion syndrome. The project utilizes a combination of somatic cell genetic and recombinant DNA technologies. The system we have established to study this disorder enables us to isolate, in interspecific somatic cell hybrids, altered chromosome 5 derivatives from persons with various deletions of this chromosome. This allows us to study the altered chromosome 5's, and DNA sequence deleted from them, apart from the normal chromosome 5 homolog present in cells from such persons. Futhermore, we have a recombinant genomic DNA library that is specific for the short arm of human chromosome 5, which will allow us to identify and localize unique DNA sequences to specific regions of this part of the human genome, including the region relevant to producing the symptoms of the cri du chat syndrome when it is deleted. This system provides a unique opportunity to gain a wealth of information about the most common human deletion syndrome and to study a complex biological and medical problem at a level that has not heretofore been possible.