MOLECULAR GENETIC STUDY OF THE CRI DU CHAT SYNDROME

这个研究项目的目的是在分子水平上研究， 已知的最常见的人类缺失综合症是CRI DU CHAT。这些研究 将包括使用重组DNA探针定义 5号染色体的短臂，当被删除时，负责 产生CRI DU CHAT的临床和表型症状 综合症。一旦在DNA水平上定义了这样一个区域，我们将尝试 鉴定产物(RNA转录本和/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CRI DU Chat综合征的人，其中缺失的染色体有 重新出现，我们将确定缺失的染色体是否 父系或母系。目前，还不能进行 这类分析适用于任何人类缺失综合症。该项目 利用体细胞遗传和重组DNA的组合 技术。我们为研究这种紊乱而建立的系统 使我们能够在种间体细胞杂交中分离改变 5号染色体衍生自具有不同此基因缺失的人 染色体。这使我们能够研究改变的5‘染色体S和dna。 从它们中删除的序列，除了正常的5号染色体同源 存在于这些人的细胞中。此外，我们有一个重组的 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 人类基因组这一部分的特定区域，包括该区域 与出现CRI DU Chat综合征的症状有关 已删除。这一系统提供了一个独特的机会，可以获得 关于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 是有可能的。

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.