FINE STRUCTURE GENETIC LINKAGE MAP OF CHROMOSOME 21 & 22

21号染色体精细结构遗传连锁图

• 批准号: 3333431
• 负责人: Jonathan L Haines
• 金额: $ 32.5万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3333431
• 关键词: DNA; chromosomes; ethnic group; gender difference; gene frequency; genetic markers; genetic recombination; linkage mapping; meiosis; molecular cloning; nucleic acid hybridization; nucleic acid probes; nucleic acid sequence; restriction mapping

Advancements in recombinant DNA technology have nurtured the growth of linkage analysis into a powerful methodology for human genetic research. Genetic linkage maps of all the chromosomes have been developed using hundreds of cloned genes and anonymous DNA sequences. Such maps further increase the power of linkage analysis to define disease gene location. However, their current utility is limited by rather low resolution and inconsistent spacing of loci. The goal of this proposal is to generate genetic linkage maps of human chromosomes 21 and 22 with a sex-averaged resolution of 1 cM. Data will be generated on 100 sibships containing over 1400 potentially informative meioses. Initial maps with resolutions slightly less than 10 cM already exist and will serve as the backbone for the high resolution maps. Probes will be obtained from all sources, including cosmid libraries. By comparison with physical mapping results (generated under separate proposals), a directed cloning strategy may be used to fill under-represented regions. Efficient methodologies for error checking and analysis of the data will significantly reduce the amount of computer time necessary. The resulting fine-structure maps will be five to ten times as precise as current maps. They will substantially increase the efficiency with which any disease gene residing on these two chromosomes can be localized, and will provide excellent starting points for direct cloning of the disease gene locus. Statistical analysis of the data will help answer questions concerning variation in recombination by sex, age, ethnic background, and familial clustering. It will also aid in the determination of appropriate parameters for interference. Prenatal and presymptomatic diagnosis of disease will be possible with accuracy almost totally dependant on the pedigree structure and clinical diagnosis, not on the markers tested. Finally, these maps will allow informative comparisons between physical and genetic maps, providing new insights into chromosome structure and organization, and facilitating the eventual sequencing of chromosomes 21 and 22.

重组 DNA 技术的进步促进了增长 连锁分析成为人类遗传的强大方法 研究。 所有染色体的遗传连锁图谱均已绘制 使用数百个克隆基因和匿名 DNA 开发 序列。 这样的地图进一步增强了联动的力量 分析以确定疾病基因位置。 然而，他们目前的 实用性受到分辨率相当低和不一致的限制 基因座的间距。 该提案的目标是生成遗传连锁图 人类 21 号和 22 号染色体，性别平均分辨率为 1 cM。 将在 100 个兄弟船舶上生成数据，其中包含 1400 多个 潜在的信息减数分裂。 带有分辨率的初始地图 略小于 10 厘米已经存在，并将作为 高分辨率地图的主干。 将获得探针 来自所有来源，包括 cosmid 库。 相比之下 物理测绘结果（根据单独的提案生成），a 定向克隆策略可用于填补代表性不足的问题 地区。 有效的错误检查和分析方法 的数据将显着减少计算机时间 必要的。 由此产生的精细结构图将是原来的五到十倍 与当前地图一样精确。 他们将大幅增加 驻留在这两个上的任何疾病基因的效率 染色体可以定位，并将提供良好的起点 直接克隆疾病基因位点。 统计 数据分析将有助于回答以下问题 重组因性别、年龄、种族背景而异 家族聚集。 它还将有助于确定 适当的干扰参数。 产前和 疾病症状前的准确诊断将成为可能 几乎完全取决于谱系结构和临床 诊断，而不是根据测试的标记物。 最后，这些地图将 允许物理图谱和遗传图谱之间的信息比较， 提供对染色体结构和组织的新见解， 并促进21号和22号染色体的最终测序。