GENES AND GENE TARGETS FROM THE DOWN SYNDROME REGION

唐人街的智力低下、身体残疾与早衰 综合征(DS)是由人类的全部或部分三倍体引起的 21号染色体(Ch21)。这种细胞遗传学定义的清晰度掩盖了一种 受未知数量基因影响的复杂病理生理学。这个 这项提议的最终目标是识别其中的一些基因和 他们的目标。提出了一种解决这一问题的新方法，该方法使用 先前产生的转基因小鼠和胚胎干细胞含有 与DS有关的CH21大基因组区域 表型，并已被操纵为酵母人工染色体 (YAC)。差异显示/逆转录酶技术 将使用聚合酶链式反应(DDRTPCR)来检测差异 位于DS区Yacs和On上的两个基因的mRNA积累 对人类YAC编码基因产物有反应的小鼠基因。这 技术提供了差异基因的可视表示 表达，并允许“捕获”辅助分子操作 不同之处。提出了一系列高通量分析来分类， 验证、映射和识别生成的cDNA。

The mental retardation, physical handicaps, and premature aging of Down syndrome (DS) are caused by a triplication of all or parts of human chromosome 21 (CH21). The clarity of this cytogenetic definition belies a complex pathophysiology impacted by an unknown number of genes. The ultimate goal of this proposal is to identify some of these genes and their targets. A novel approach to this problem is proposed, which uses previously generated transgenetic mice and embryonic stem cells containing large genomic regions of CH 21 that have been implicated in the DS phenotype and have been manipulated as yeast artificial chromosomes (YACs). The technique of differential display/reverse transcriptase polymerase chain reaction (DDRTPCR) will be used to detect differential mRNA accumulation from both genes located on the DS region YACs, and on mouse genes that respond to human YAC-encoded gene products. This technique provides a visual representation of differential gene expression, and allows the "capture" aid molecular manipulation of the differences. A series of high-throughput assays are proposed to classify, authenticate, map, and identify resultant cDNAs.