ABNORMAL HEMOGLOBIN SYNTHESIS--MECHANISM & DETECTION

我们计划开发镰状细胞性贫血的产前诊断方法，并 地中海贫血，研究人类群体中镰刀基因的进化，并 探讨糖尿病患者珠蛋白产生异常的分子机制 地中海贫血。在产前诊断中，我们将寻找DNA的多态性 可用于镰刀基因与水稻的连锁分析的序列 不同类型的β地中海贫血基因。我们将设计方法来分析 镰刀状突变中的核苷酸直接改变。我们还将使用 用分子克隆技术研究沙门氏菌核苷酸序列的差异 S和C基因，确定其进化谱系。在贝塔地中海贫血患者中，我们 计划寻找不同类型的无义突变作为贝塔病毒的原因 地中海贫血。我们将首先利用抑制子tRNA检测无稽之谈 突变并通过克隆基因和序列来确定确切的突变 分析。在阿尔法地中海贫血中，我们将研究其产生机制 通过DNA分子克隆的非缺失型阿尔法地中海贫血， 通过序列分析确定它们的结构，并分析 这些基因在体外系统中的功能。

We plan to develop methods for the prenatal diagnosis of sickle cell anemia and thalassemia, to study evolution of the sickle gene in human populations, and to investigate the molecular mechanism underlying abnormal globin production in thalassemia. In prenatal diagnosis, we will search for polymorphism in DNA sequence which can be used for linkage analysis of the sickle gene and the different types of beta thalassemia genes. We will devise methods to analyze directly the nucleotide change in the sickle mutation. We will also use molecular cloning to study the divergence between the nucleotide sequence of the S and C gene to determine their evolutionary lineage. In beta thalassemia, we plan to search for different types of nonsense mutations as the cause for beta thalassemia. We will first utilize the suppressor tRNA assay to detect nonsense mutation and determine the exact mutations by cloning the gene and sequence analysis. In alpha thalassemia, we will study the mechanism of production of the non-deletion type of alpha thalassemia by molecular cloning of the DNA, determination of their structures by sequences analysis, and assaying the function of these genes in in vitro systems.