GENE ISOLATION AND FUNCTIONAL ANALYSIS OF 21Q11-21 RELATING TO DOWN SYNDROME

21Q11-21有关唐氏综合症的基因分离和功能分析

• 批准号: 6301890
• 负责人: FA-TEN KAO
• 金额: $ 17.74万
• 依托单位: ELEANOR ROOSEVELT INST FOR CANCER RES
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6301890
• 关键词: Downs syndrome; HeLa cells; animal genetic material tag; behavioral /social science research tag; chromatin; chromosome 21; clone cells; cognition; complementary DNA; computer assisted sequence analysis; fluorescent in situ hybridization; gene expression; genetic library; genetic mapping; genetic regulation; genome; human genetic material tag; mental retardation; methylation; neurogenesis; northern blottings; nucleic acid sequence; plasmids; polymerase chain reaction

The overall aim of this sub-project focuses on gene isolation and molecular analysis of the proximal half of the long arm of human chromosome 21 including 21q11-21, a region under-exploited but associated with mental retardation of individuals with Down Syndrome. The specific objectives are: (1) Isolation, characterization and sequencing of unique sequence microclones from microdissection libraries constructed specifically for the 21q11-21 region; (2) Homology analysis between the unique copy microclones and know genes or cDNAs; (3) refined regional mapping of microclones within 21q11-21; (4) comparative mapping between 21q11-21 and the mouse genome; (5)methylation analysis of 21q11-21; (6) chromatin condensation analysis of 21q11-21 during interphase; (7) isolation and characterization of CDNAS from 21q11-21; (8) gene expression analysis using demetylation strategies; (9) study of the genomic structure and organization of 21q11-21 relating to its function and regulation; (1) analysis of genes and cDNAs identified in 21q11-21 for possible involvement in cognitive-neural developmental deficits in mental retardation. Promising progress towards most of these objectives have already been made to demonstrate that the 21q11-21 region indeed have genes which may be important to Down syndrome. These studies also showed that 21q11-21 has unique structures which may be crucial to the regulation of the genes residing in this region. Thus, gene isolation and better understanding of the regulation and expression of 21q11-21 should be important to the unraveling of the etiology of mental retardation in Down syndrome and for possible early intervention of this devastating pathology.

该子项目的总体目标侧重于基因分离和 人类长臂近半部分的分子分析 21 号染色体，包括 21q11-21，一个未充分利用但相关的区域 唐氏综合症患者智力低下。具体的 目标是： (1) 独特的分离、表征和测序 来自构建的显微切割文库的序列微克隆 专门针对 21q11-21 区域； (2) 之间的同源性分析 独特的拷贝微克隆和已知基因或cDNA； （三）精细化区域 21q11-21 内的微克隆图谱； (4) 比较映射 21q11-21 和小鼠基因组； (5)21q11-21甲基化分析； (6) 间期21q11-21染色质凝聚分析； (7) 来自 21q11-21 的 CDNAS 的分离和表征； (8)基因表达 使用去甲基化策略进行分析； (9)基因组结构的研究 21q11-21 与其职能和监管相关的组织； (1) 分析 21q11-21 中确定的基因和 cDNA，以了解可能的情况 参与心理认知神经发育缺陷 迟缓。大多数这些目标都取得了可喜的进展 已经证明 21q11-21 区域确实有 可能对唐氏综合症很重要的基因。这些研究还表明 21q11-21 具有独特的结构，这可能对监管至关重要 存在于该区域的基因。因此，基因分离和更好 对21q11-21的调控和表达的理解应该是 对于揭示唐氏智力低下的病因很重要 综合症以及可能的早期干预这种毁灭性的 病理。