HETEROZYGOTE DIAGNOSIS IN MYOTONIC MUSCULAR DYSTROPHY

强直性肌营养不良症的杂合子诊断

• 批准号: 3400156
• 负责人: ALLEN D ROSES
• 金额: $ 24.7万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-07-01 至 1991-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3400156
• 关键词: DNA; autosomal dominant trait; biological polymorphism; chromosomes; complement; density gradient ultracentrifugation; disease /disorder proneness /risk; fibroblasts; flow cytometry; gene expression; genetic library; genetic manipulation; genetic markers; genetic recombination; genetic registry /resource /referral center; heterozygote; human tissue; immunogenetics; inborn metabolism disorder diagnosis; leukocyte activation /transformation; linkage mapping; molecular cloning; myotonic dystrophy; nucleic acid sequence; prenatal diagnosis

Myotonic muscular dystrophy (DM) is the most common form of genetic muscular dystrophy affecting adults and children. The gene for DM is located near the centromere on chromosome 19. DM and apolipoprotein C11 (apoC11) have been closely linked using two apoC11 DNA polymorphisms to test linkage in our large, multigenerational DM pedigrees. Several new anonymous restriction fragment length polymorphisms (RFLPs) have been isolated from chromosome 19 enriched libraries and are being tested for linkage to DM. We propose to continue to identify tightly linked RFLPs and to initiate chromosome walking to define the DM gene. We propose to use enriched chromosome 19 libraries prepared in phages EMBL3 and charon 35, and the LORIST vector for the chromosome walk, initiating at the tightest available DNA probe. LORIST has the advantage over other cosmid vectors in that it maintains a higher and more constant copy number with large insert size, and can rapidly discriminate the opposing ends of the insert facilitating rapid direction specific chromosome walks. We propose to map chromosome 19 in the area of DM and to identify the DM gene using multiple strategies. Our goal is to design rational treatments of DM, perhaps taking advantage of the variable expressivity and penetrance that characterize this late-age-of-onset disorder to prevent symptoms and signs in presymptomatic heterozygotes.

强直性肌营养不良症(DM)是最常见的遗传病 影响成人和儿童的肌营养不良症。糖尿病的基因是 位于19号染色体着丝粒附近的DM与载脂蛋白C11 (ApoC11)通过两个apoC11 DNA多态紧密连锁 在我们的大型、多代DM家系中测试连锁。几个新的 匿名限制片段长度多态(RFLP)已经被 从19号染色体丰富的文库中分离出来，正在进行检测 与DM的链接。我们建议继续确定紧密联系的限制性区域有限责任公司和 启动染色体行走来定义DM基因。我们建议使用 在噬菌体EMBL3和Charon 35中制备的浓缩19号染色体文库， 以及用于染色体行走的LORIST载体，从最紧密的位置开始 可用的DNA探针。LORIST在以下方面比其他余弦向量具有优势 它在大插入的情况下保持了更高和更恒定的拷贝数 大小，并能快速区分插入件的相对两端 促进特定方向的染色体快速行走。我们建议绘制一张地图 19号染色体在DM区的定位及对DM基因的鉴定 战略。我们的目标可能是设计合理的糖尿病治疗方法。 利用可变的表现力和透视度， 描述这种起病晚的疾病以预防症状和体征 在症状前杂合子中。