ABNORMAL HEMOGLOBIN SYNTHESIS-MECHANISM & DETECTION

血红蛋白合成机制异常

• 批准号: 3483151
• 负责人: YUET Wai KAN
• 金额: $ 32.14万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-08-01 至 1991-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3483151
• 关键词: biological polymorphism; bone marrow; disease /disorder model; gene expression; gene mutation; gene therapy; genetic disorder diagnosis; genetic manipulation; genetic regulation; genetic transduction; genetically modified animals; hemoprotein biosynthesis; human subject; laboratory mouse; molecular cloning; molecular pathology; nucleic acid hybridization; nucleic acid sequence; orphan disease /drug; point mutation; population genetics; prenatal diagnosis; sickle cell anemia; structural genes; thalassemia; tissue /cell culture; transfer RNA

This research proposal deals with the continued investigation of the hemoglobinopathies and thalassemia on a molecular level. It will concentrate on four areas: (1) Continued development of approaches to prenatal diagnosis for Beta thalassemia by DNA analysis. During the past few years, direct methods of prenatal diagnosis of Alpha thalassemia and sickle cell anemia by DNA analysis have become available. The molecular lesions responsible for Beta thalassemia are diverse and it is therefore important to determine the type of mutation present in a given area. With this knowledge, specific methods of prenatal diagnosis could be designed. The implementation of diagnosis by DNA analysis will improve the safety and accuracy of the test. (2) The molecular lesions causing the thalassemia mutations will continue to be characterized. Such studies may further our understanding of the control of globin gene expression. Unidentified Beta thalassemia genes obtained from the work in (1) will be characterized. Interesting mutations which may provide insight into the control of globin synthesis, and spontaneous mutations will also be studied. (3) The transgenic mouse model will be used to study regulation of human globin gene expression. This model may provide a means for studying tissue-specific and developmental controls of human globin gene expression. (4) The use of suppressor tRNAs as a means of overcoming the nonsense mutation in Beta thalassemia will be investigated. Human suppressor tRNA genes that insert lysine or glutamine into the UAG codon will be introduced into erythroid cells from patients with the Beta17 nonsense and Beta39 nonsense mutations.

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