GENES AND GENE TARGETS FROM THE DOWN SYNDROME REGION

唐氏综合症区域的基因和基因靶点

• 批准号: 2332229
• 负责人: Michael J Shamblott
• 金额: $ 2.44万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-02-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2332229
• 关键词: Downs syndrome; amyloid proteins; animal genetic material tag; artificial chromosomes; complementary DNA; developmental genetics; embryonic stem cell; genetically modified animals; hybrid cells; laboratory mouse; messenger RNA; nucleic acid sequence; polymerase chain reaction; superoxide dismutase

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.

唐氏症的智力低下、肢体残疾和早衰 综合征（DS）是由三倍的所有或部分的人类 21号染色体（CH 21）。这种细胞遗传学定义的清晰性掩盖了 受未知数量基因影响的复杂病理生理学。 的 这项提议的最终目标是确定其中一些基因， 他们的目标 提出了一种解决这个问题的新方法，该方法使用 先前产生的转基因小鼠和胚胎干细胞， CH 21的大基因组区域与DS有关 表型，并已被操纵为酵母人工染色体 （YAC）。 差异显示/逆转录技术 聚合酶链反应（DDRTPCR）将用于检测差异 来自位于DS区域YAC上的两种基因的mRNA积累，以及来自位于 小鼠基因对人类YAC编码的基因产物有反应。 这 技术提供了差异基因可视化表示 表达，并允许“捕获”辅助分子操纵的表达。 差异 提出了一系列高通量测定来分类， 鉴定、定位和鉴定所得cDNA。