CORE--CLINICAL-MOLECULAR CORE

核心--临床-分子核心

• 批准号: 5212554
• 负责人: JULIE RUTH KORENBERG
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5212554
• 关键词: Downs syndrome; aneuploidy; artificial chromosomes; biomedical facility; chromosome 21; clone cells; genetic manipulation; human tissue; in situ hybridization; nucleic acid probes; pulsed field gel electrophoresis; southern blotting; trisomy

Down syndrome (DS) is a major cause of mental retardation and congenital heart disease (CHD). Little is known about the molecular events that cause the DS phenotype. The ultimate goal of the proposed research in the program is to define the genes and their functions responsible for the phenotypic features of DS. As a first step, the specific aims of the Clinical Molecular Core are designed to molecularly define the chromosomal regions deleted or duplicated in patients with partial aneuploidy 21 and specific phenotypic features. Three panels including more than 100 cell lines have been assembled. New cases are added at a rate of 10 per year. Each panel now includes a series of overlapping duplications or deletions that span the length of chromosome 21. This panel includes 53 individuals with partial trisomy 21 or partial monosomy 21. The analysis of this panel will combine definition of phenotype with high resolution cytogenetics, fluorescence in situ hybridization, and quantitative Southern blot dosage analysis. The specific aim is delineation of a DS (trisomy 21) phenotypic map. Molecular definition of the duplicated regions and the breakpoints will be determined by quantitative Southern blot analysis suing chromosome 21 unique DNA sequences. Phenotypic features will be established according to the NICHD DS conference (4/90). The panel is informative for holoprosencephaly, mental retardation, skeletal dysplasia, immune deficits, DS CHD, duodenal stenosis, and leukemia in addition to the physical, radiological, cognitive, neurologic and laboratory features of DS. A database will be used to record clinical, cytogenetic and molecular data. Chromosomal constitution will be determined using high resolution cytogenetic analysis and in situ hybridization. The core will provide a basic resource of partially aneuploid individuals and their cell lines with which to study the expression of chromosome 21 and the role of specific genes in determining organismal phenotype.

唐氏综合症（DS）是智力低下和先天性的主要原因 心脏病（CHD）。 关于分子事件知之甚少 导致DS表型。 拟议研究的最终目标 该程序是定义基因及其功能 DS的表型特征。 作为第一步， 临床分子核设计为分子定义 部分患者删除或复制染色体区域 非整倍性21和特定的表型特征。 包括三个面板 已经组装了100多个细胞系。 新案件被添加 每年10次。 现在每个面板都包含一系列重叠 跨越染色体21的长度的重复或删除。 面板包括53个患有部分三体术的人或部分单子 21。该面板的分析将结合表型的定义与 高分辨率的细胞遗传学，荧光原位杂交和 定量南部印迹剂量分析。 具体目的是 DS（三体术21）表型图的描述。 分子定义 重复的区域和断点将由 定量Southern印迹分析提醒染色体21独特的DNA 序列。 表型特征将根据 NICHD DS会议（4/90）。 小组很有意义 全脑脑，智力低下，骨骼发育不良，免疫 缺陷，DS冠心病，十二指肠狭窄和白血病。 物理，放射学，认知，神经和实验室特征 DS。 数据库将用于记录临床，细胞遗传学和 分子数据。 染色体宪法将使用高 分辨率细胞遗传学分析和原位杂交。 核心意愿 提供部分非整倍体个体及其的基本资源 研究染色体21和的细胞系 特定基因在确定生物表型中的作用。