HETEROZYGOTE DIAGNOSIS IN MYOTONIC MUSCULAR DYSTROPHY

强直性肌营养不良症的杂合子诊断

• 批准号: 3400157
• 负责人: ALLEN D ROSES
• 金额: $ 24.71万
• 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 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3400157
• 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）是最常见的遗传性肌营养不良症。 影响成人和儿童的肌肉萎缩症。 糖尿病的基因是 位于19号染色体的着丝粒附近。 糖尿病与载脂蛋白C11 （apoC11）已经使用两个apoC11 DNA多态性与 在我们的大型多代DM家系中测试连锁。 几个新 匿名限制性片段长度多态性（RFLP）已经被 从19号染色体富集文库中分离，并正在测试 与DM的联系 我们建议继续识别紧密连锁的RFLPs， 启动染色体步移来确定DM基因。 我们建议使用 富集的19号染色体文库制备于EMBL3和charon 35中， 和LORIST载体的染色体行走，开始在最紧密的 可用的DNA探针。 LORIST与其他粘粒载体相比具有以下优点： 它保持更高和更恒定的拷贝数与大插入 尺寸，并且可以快速区分插入件的相对端部 促进快速方向特异性染色体游走。 我们建议绘制 在DM区域的19号染色体上，并使用多重PCR技术鉴定DM基因。 战略布局 我们的目标是设计合理的糖尿病治疗方法， 利用了可变的表现力和灵活性， 描述这种迟发性疾病，以防止症状和体征 在症状前杂合子中。