MOLECULAR ANALYSIS OF HUMAN CHROMOSOME 21 AND 3

人类 21 号和 3 号染色体的分子分析

• 批准号: 3073542
• 负责人: KATHELEEN GARDINER
• 金额: $ 5.92万
• 依托单位: ELEANOR ROOSEVELT INST FOR CANCER RES
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-01 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3073542
• 关键词: Alzheimer's disease; Downs syndrome; artificial chromosomes; chromosome disorders; chromosome translocation; chromosomes; gel electrophoresis; gene expression; genetic library; genetic mapping; human genetic material tag; human tissue; leukemia; molecular cloning; molecular genetics; neoplasm /cancer genetics; nucleic acid sequence; trisomy

Specific rearrangements of human chromosome 3 are associated with malignancies such as small cell lung cancer, renal cell carcinoma, leukemia, and several developmental disorders. Human chromosome 21 is associated with Down Syndrome, leukemia and Alzheimer's Disease. These two chromosome contain approximately 200 million and 50 million base pairs of DNA, respectively, and therefore together potentially contain between 4,000 and 8,000 genes. Fewer than 100 genes in total have been identified, meaning that much valuable biological information is not easily accessible. In order to increase our understanding of chromosomal organization and to isolate biologically important genes, the specific aims of this proposal are to construct yeast artificial chromosome (YAC) libraries and compositional maps for chromosomes 3 and 21. The compositional maps will provide information on gene rich regions and will allow the cloning of these and other unusual chromosomal regions. The YAC libraries will be screened with unique sequences that have been placed on the pulsed field maps, and with cDNAs from various cell lines and tissues. This will result in i) rapid regional localization of YAC clones, ii) identification of additional unique sequences for pulsed field linkage, iii) generation of additional probes for the search for chromosomal translocation breakpoints, and iv) identification of expressed sequences, including some in the vicinity of translocation breakpoints. Long term objectives include: i) characterization of genes affected by the 8; 21 breakpoint seen in AML-M2, as well as those from others, ii) the development of a series of large insert clones to span large chromosomal regions, iii) the generation of well characterized YACs useful for transgenic mouse studies.

人类3号染色体的特定重排与 小细胞肺癌、肾细胞癌、 白血病和几种发育障碍。人类21号染色体是 与唐氏综合症、白血病和阿尔茨海默病有关。这两个 染色体包含大约2亿和5000万个碱基对 DNA，因此加在一起可能含有4000 和8000个基因。总共只发现了不到100个基因， 这意味着许多有价值的生物信息并不容易获取。 为了增加我们对染色体组织的了解，并 分离生物上重要的基因，这项提议的具体目的 是构建酵母人工染色体(YAC)文库和 3号和21号染色体的组成图谱。构图将会 提供有关基因丰富区域的信息，并将允许克隆 这些和其他不寻常的染色体区域。青年会图书馆将会是 用放置在脉冲场上的独特序列进行筛选 与来自不同细胞系和组织的cDNA进行比较。这将导致 在i)YAC克隆的快速区域定位中，ii)识别 用于脉冲场链接的附加唯一序列，iii)生成 用于搜索染色体易位断裂点的额外探针， 以及iv)表达序列的鉴定，包括在 易位断点附近。长期目标包括：i) AML-M2中出现的8；21断裂点影响的基因的特征， 以及来自其他公司的那些，II)开发了一系列大型 插入克隆以跨越大的染色体区域，III)产生 对转基因小鼠研究有用的具有良好特性的YAC。