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

这个子项目的总体目标集中在基因分离和 人长臂近端半部的分子分析 21号染色体包括21q11-21，这是一个开发不足但相关的区域 唐氏综合征患者的精神发育迟滞。具体的 目的是：(1)独特的分离、鉴定和测序 构建的微切割文库中的序列微克隆 具体针对21q11-21区域；(2)同源性分析 独特的复制微克隆和已知基因或cDNA；(3)精制区域 21q11-21微克隆的作图；(4)比较作图 21q11-21和小鼠基因组；(5)21q11-21的甲基化分析；(6) 21q11-21间期染色质缩合分析(7) 21q11-21中cDNA的分离与鉴定；(8)基因表达 使用去甲基化策略进行分析；(9)基因组结构研究 以及21q11-21与其职能和监管有关的组织；(1) 21q11-21中可能存在的基因和cDNA分析 心理障碍与认知神经发育缺陷的关系 智力迟缓。在实现这些目标中的大多数方面取得了可喜的进展 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，这可能对调控至关重要 居住在这个区域的基因。因此，基因分离和更好地 理解21q11-21的调控和表达应 对揭开唐代精神发育迟滞病因的重要意义 综合症和可能的早期干预这一毁灭性的 病理学。

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.