ABNORMAL HEMOGLOBIN SYNTHESIS--MECHANISM & DETECTION

血红蛋白合成异常--机制

• 批准号: 3151021
• 负责人: YUET Wai KAN
• 金额: $ 27.22万
• 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 1986-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3151021
• 关键词: African American; affinity chromatography; biological polymorphism; cell free system; chemical structure function; diagnosis quality /standard; embryo /fetus; evolution; gene mutation; genetic disorder diagnosis; genetic manipulation; hemoprotein biosynthesis; human subject; human tissue; messenger RNA; molecular cloning; molecular pathology; nucleic acid sequence; orphan disease /drug; prenatal diagnosis; sickle cell anemia; structural genes; thalassemia

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.

我们计划开发镰状细胞性贫血的产前诊断方法， 地中海贫血，研究人类群体中镰刀基因的进化， 研究异常珠蛋白产生的分子机制， 地中海贫血 在产前诊断中，我们将寻找DNA的多态性 可用于镰状基因和突变体的连锁分析的序列， 不同类型的β地中海贫血基因 我们将设计方法来分析 直接影响镰刀突变的核苷酸变化。 我们还将使用 通过分子克隆研究了 S和C基因来决定它们的进化谱系。 在β地中海贫血中，我们 计划寻找不同类型的无义突变作为β的原因， 地中海贫血 我们将首先利用抑制tRNA检测来检测无义 突变，并通过克隆基因和序列确定确切的突变 分析. 在α地中海贫血中，我们将研究产生 通过DNA的分子克隆获得非缺失型α地中海贫血， 通过序列分析确定它们的结构，并测定 这些基因在体外系统中的功能。

项目成果

Application of DNA polymorphisms for prenatal diagnosis of beta thalassemia in Chinese.

DNA多态性在中国人β地中海贫血产前诊断中的应用

• DOI: 10.1002/ajh.2830250407
• 发表时间: 1987
• 期刊: American journal of hematology
• 影响因子: 12.8
• 作者: Chan,V;Chan,TK;Ghosh,A;Wong,LC;Ma,HK;Kan,YW;Todd,D
• 通讯作者: Todd,D

Ferrara beta 0 thalassaemia caused by the beta 39 nonsense mutation.

Ferrara β 0 地中海贫血是由 β 39 无义突变引起的。

• DOI: 10.1038/307076a0
• 发表时间: 1984
• 期刊: Nature
• 影响因子: 64.8
• 作者: Pirastu,M;delSenno,L;Conconi,F;Vullo,C;Kan,YW
• 通讯作者: Kan,YW

Prenatal diagnosis by DNA analysis.

通过 DNA 分析进行产前诊断。

• 发表时间: 1982
• 期刊: Birth defects original article series
• 作者: Kan,YW;Chang,JC;Dozy,AM
• 通讯作者: Dozy,AM

The molecular basis of beta-thalassemia in Lebanon: application to prenatal diagnosis.

黎巴嫩β-地中海贫血的分子基础：在产前诊断中的应用。

• 发表时间: 1987
• 期刊: Blood
• 影响因子: 20.3
• 作者: Chehab,FF;DerKaloustian,V;Khouri,FP;Deeb,SS;Kan,YW
• 通讯作者: Kan,YW

Initiation codon mutation as a cause of alpha thalassemia.

起始密码子突变是α地中海贫血的原因。

• 发表时间: 1984
• 期刊: The Journal of biological chemistry
• 作者: Pirastu,M;Saglio,G;Chang,JC;Cao,A;Kan,YW
• 通讯作者: Kan,YW