GENETIC STUDIES OF NORTH CAROLINA MUSCULAR DYSTROPHY

北卡罗来纳州肌营养不良症的遗传学研究

• 批准号: 3086823
• 负责人: KENT W SMALL
• 金额: $ 8.8万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3086823
• 关键词: artificial chromosomes; autosomal dominant trait; chromosome walking; complementary DNA; family genetics; gel electrophoresis; genetic disorder diagnosis; genetic polymorphism; human genetic material tag; human subject; linkage mapping; lymphoblast; nucleic acid hybridization; nucleic acid probes; restriction fragment length polymorphism; retina degeneration; subtraction hybridization

The general objectives of this proposal are to gain educational and basic laboratory training in molecular genetic methods and human genetics in general, and apply them to ophthalmologic disorders in order to substantively contribute to the understanding and possible treatment of inherited ocular disorders. These general goals will be specifically met by attending courses and conferences as described at the end of Section 2 and by performing gene linkage studies on North Carolina Macular Dystrophy (NCMD) (previously called dominant progressive foveal dystrophy of Lefler, Wadsworth and Sidbury). This dominantly inherited retinal disorder, which comprises over a 1,400 member kindred, has an infantile onset, complete penetrance and variable expressivity, and affects primarily central vision causing 20/200 visual acuity in severely affected individuals. The fundu- scopic appearance of the milder cases closely resembles the appearance of age-related macular degeneration (AMD). A basic molecular understanding of NCMD may shed light on the more common problem of AMD, the most common cause of legal blindness in the American elderly. Briefly, the techniques employed to perform gene-linkage analysis are now well established. First, the pedigree is ascertained and blood collected from the significant family members, to set up lymphoblasts cell lines which provide a source of DNA for study. Then, using restriction enzymes and cDNA probes the pedigree is examined for polymorphisms. Linkage analysis is then performed in an effort to establish the chromosomal location of the gene for NCMD. Once linkage to a chromosome is found, fine mapping techniques (macro restriction mapping, field inversion gel electrophoresis, detection of Hpall tiny fragment islands, yeast artificial chromosomes, hopping libraries, and subtraction hybridization) will be used. In addition, the identification of a number of highly polymorphic DNA probes tightly linked to NCMD has important clinical implications in genetic counseling and prenatal diagnosis.

这项建议的总体目标是获得教育和基本 分子遗传学方法和人类遗传学实验室培训 普通，并将其应用于眼科疾病，以便 对理解和可能的治疗有实质性贡献 遗传性眼病。这些一般目标将具体由以下人员实现 参加第2节末尾所述的课程和会议 通过对北卡罗来纳州黄斑营养不良进行基因连锁研究 (NCMD)(以前称为遗传性进行性黄斑中心凹营养不良， 沃兹沃斯和西德伯里)。这种以遗传性为主的视网膜疾病， 由1,400多名成员组成的亲属，有婴儿发病，完整 外显性和可变表现力，主要影响中央视觉 对受严重影响的人造成20/200的视力。基金会-- 较轻病例的镜检外观与 老年黄斑变性(AMD)。对分子生物学的基本认识 NCMD可能会揭示更常见的AMD问题，最常见的 美国老年人法律失明的原因。简而言之，这些技术 用来进行基因连锁分析的方法现在已经得到了很好的证实。第一, 血统被确定，并从重要的家庭中采集血液 成员们，建立淋巴母细胞系，为DNA提供来源 为了学习。然后，使用限制性内切酶和cdna探针，谱系是 检查是否存在多态。然后进行连锁分析，努力 目的：确定NCMD基因的染色体定位。一旦链接到 染色体被发现，精细作图技术(宏观限制作图， 现场反转凝胶电泳法检测HpALL微片段 岛、酵母人工染色体、跳跃文库和减法 杂交)将被使用。此外，还识别了一些 与NCMD紧密连锁的高度多态DNA探针具有重要的临床意义 遗传咨询和产前诊断的意义。