GENE EXPRESSION IN SOMATIC CELLS IN THE AGING PROCESS

衰老过程中体细胞的基因表达

• 批准号: 3114017
• 负责人: DAVID PATTERSON
• 金额: $ 30.22万
• 依托单位: ELEANOR ROOSEVELT INST FOR CANCER RES
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-06-01 至 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3114017
• 关键词: Alzheimer's disease; Huntington's disease; Werner's syndrome; aging; amyloidosis; amyotrophic lateral sclerosis; autosomal dominant trait; cell fusion; cell transformation; chromosome translocation; complementary DNA; cytogenetics; gel electrophoresis; gene expression; genetic manipulation; genetic mapping; genetic transcription; genetic translation; hamsters; linkage mapping; microscopy; molecular cloning; mutant; nucleic acid probes; nucleic acid sequence; oxidative phosphorylation; premature aging; purine /pyrimidine metabolism; purine nucleotides; tissue /cell culture; yeasts

The long term objectives of this research are to understand the role of specific genes in diseases associated with aging, especially Alzheimer disease (AD) and amyotrophic lateral sclerosis (ALS). Information relevant to Parkinson disease (PD) and Huntington disease (HD) may also be obtained. Familial AD has recently been associated with genetic loci on chromosomes 19 and 21, and familial ALS with a locus on chromosome 21. A high resolution physical and genetic map of the relevant regions of these chromosomes will be developed using somatic cell hybrids and the isolation of many new polymorphic DNA probes. These will be used to refine the location of the AD and ALS genes. Physical maps consisting of overlapping contiguous DNA clones in yeast artificial chromosomes (YACs) and cosmids will be constructed for the relevant chromosomal regions. Attempts will be made to identify, isolate, and characterize the relevant genes using this information. In a complementary approach, a set of candidate genes involved in purine nucleotide metabolism and oxidative phosphorylation will be regionally mapped, converted to highly polymorphic DNA probes, and assessed for linkage to AD, ALS, HD and perhaps PD. The possible role of these biochemical pathways in these diseases will be assessed biochemically in cells from affected individuals. It is hoped that in this way the genes involved in at least the familial forms of these disorders will be identified and isolated, and that this will lead to more effective diagnosis, treatment, and prevention of these devastating diseases.

这项研究的长期目标是了解 与衰老相关的疾病中的特定基因，尤其是阿尔茨海默氏症 疾病（AD）和肌萎缩性外侧硬化症（ALS）。 信息相关 还可以获得帕金森病（PD）和亨廷顿疾病（HD）。 家族广告最近与染色体上的遗传基因座有关 19和21，以及在21染色体上的基因座的家族性ALS。 解决这些相关区域的物理和遗传图 染色体将使用体细胞杂种和分离开发 在许多新的多态性DNA探针中。 这些将用于完善 广告和ALS基因的位置。 物理图由重叠组成 酵母人工染色体（YAC）和宇宙中的连续DNA克隆 将为相关染色体区域构建。 尝试将是 使用此识别，隔离和表征相关基因 信息。 在补充方法中，一组候选基因 参与嘌呤核苷酸代谢和氧化磷酸化的涉及 在区域映射，转换为高度多态DNA探针，然后 评估与AD，ALS，HD甚至PD的联系。 可能的作用 这些疾病中的这些生化途径将在生化上评估 在受影响个体的细胞中。 希望以这种方式这些基因 至少参与这些疾病的家族形式将是 确定和孤立，这将导致更有效 诊断，治疗和预防这些毁灭性疾病。