ISOLATION OF THE HUNTINGTON'S DISEASE GENE

亨廷顿病基因的分离

• 批准号: 2265610
• 负责人: JOHN J WASMUTH
• 金额: $ 26.7万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-02-01 至 1998-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2265610
• 关键词: Huntington's disease; alleles; complementary DNA; gene expression; gene mutation; genetic crossing over; genetic mapping; genetic markers; genetic recombination; heterozygote; homozygote; human genetic material tag; human tissue; hybrid cells; linkage mapping; molecular cloning; molecular genetics; molecular pathology; nucleic acid probes; nucleic acid sequence; nucleic acid structure; tissue /cell culture; yeasts

The long term goals of this project are to isolate the Huntington's disease (HD) gene, identify the most common mutation in the gene which causes the disease and, ultimately, understand at the molecular level how a mutant allele at this locus produces the neuropathology of the disease in heterozygotes. A combination of physical mapping strategies will be employed to compile a very high resolution physical map of a region of about 2.5 Mb of DNA which now appears to be the most narrowly defined location of the disease gene. This will include several approaches to rapidly isolate and map many new DNA probes throughout this segment of chromosomal band 4p16.3. Somatic cell hybrids which retain chromosomes 4 from several important recombinants with HD will be isolated and extensively characterized. This provides a means for unequivocal haplotyping of a large number of polymorphic loci which will allow a more precise locilization for the disease gene to be made. All of the DNA from the minimal physical region shown to contain the HD gene will be isolated in overlapping cosmid and YAC clones. The cloned DNA will be thoroughly examined to identify genomic sequences likely to represent transcribed regions. Full lengih cDNA clones and genomic clones representing candidates for the HD gene will be isolated and used to compare the structure, sequence and expression of these genes in normal individuals, HD heterozygotes and HD homozygotes in order to identify a specific alteration which represents the most common HD mutation. The achievement of this goal will eventually lead to an understanding of the function of the normal HD gene produce and provide insight into how the presence of a mutant gene product disorder. This information will hopefully point to possible completely prevent the onset of symptoms.

这个项目的长期目标是分离亨廷顿舞蹈症