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: 3315741
• 负责人: JOHN J WASMUTH
• 金额: $ 13.81万
• 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 1987-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3315741
• 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 recombination; heterozygote; human population genetics; human tissue; hybrid cells; messenger RNA; molecular pathology; nucleic acid sequence

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.

该研究项目的目的是在分子水平上研究， 最常见的人类缺失综合症，叫聊天。 这些研究 将包括定义，使用重组DNA探针， 5号染色体的短臂，当被删除时， 产生了猫叫的临床和表型症状 综合征 一旦在DNA水平上确定了这样的区域，我们将尝试 以鉴定产物（RNA转录物和/或其多肽 翻译产物）的基因定位到这个表型 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，其中缺失的染色体具有 重新出现，我们将确定删除的染色体是否是 父亲或母亲的起源。 目前，还不能履约 对任何人类缺失综合征的分析。 项目 利用体细胞遗传和重组DNA的组合， 技术. 我们建立的研究这种疾病的系统 使我们能够在种间体细胞杂交中分离出改变的 5号染色体衍生物的人与各种删除这个 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号染色体同源物外， 存在于这些人的细胞中。 福伊特，我们有一个重组体 人类染色体短臂特异性基因组DNA文库 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 与产生Cri du Chat综合征的症状有关， 的页面不存在或 该系统提供了一个独特的机会，以获得丰富的 关于最常见的人类缺失综合征的信息，并研究 复杂的生物学和医学问题， 是可能的。