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

该分项目的总体目标是基因分离， 人长臂近端的分子分析 21号染色体，包括21 q11 -21，一个未被开发但相关的区域， 患有唐氏综合症的人的智力迟钝。具体 目的是：（1）分离，表征和测序独特的 从构建的显微切割文库中获得序列微克隆 特异性地针对21 q11 -21区域;（2）在21 q11 -21区域之间的同源性分析。 独特拷贝的微克隆和已知基因或cDNA;（3）精确的区域性 21 q11 -21内微克隆的定位;（4）之间的比较定位 21 q11 -21和小鼠基因组;（5）21 q11 -21的甲基化分析;（6） 间期21 q11 -21染色质凝聚分析;（7） 从21 q11 -21分离和表征CDNAS;（8）基因表达 使用去甲基化策略的分析;（9）基因组结构的研究 （1）与其职能和监管有关的21 q11 -21组织; 分析21 q11 -21中鉴定的基因和cDNA， 参与认知神经发育缺陷的心理 迟钝在实现其中大多数目标方面取得了可喜的进展， 已经证明21 q11 -21地区确实有 可能对唐氏综合症很重要的基因这些研究还表明， 21 q11 -21具有独特的结构， 这个区域的基因。因此，基因分离和更好 了解21 q11 -21的调控和表达， 对唐氏症精神发育迟滞的病因学的揭示很重要， 综合征和可能的早期干预，这种毁灭性的 病理

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.