TEST TO SCREEN FOR ALPHA-THALASSEMIA-1 IN ADULTS

成人 A-地中海贫血-1 筛查测试

• 批准号: 2222654
• 负责人: RONALD A SIMKINS
• 金额: $ 25万
• 依托单位: ISOLAB, INC.
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2222654
• 关键词: China; United States; blood chemistry; blood disorder diagnosis; diagnosis design /evaluation; diagnosis quality /standard; enzyme linked immunosorbent assay; erythrocytes; flow cytometry; gene deletion mutation; genetic disorder diagnosis; hemoglobin H; high performance liquid chromatography; human subject; mass screening; monoclonal antibody; polymerase chain reaction; southeast Asia; thalassemia; western blottings

The genetic disorder alpha-thalassemia-1 is found with highest frequency in individuals of southeast Asian ancestry. While the heterozygous form may have no adverse health effects except for slight anemia, the homozygous condition (known as hydrops fetalis) causes fetal death. There is no readily available clinical assay to screen adults for this trait. However, it has been reported that carriers of the alpha-thalassemia-1 gene produce small quantities of the embryonic hemoglobin zeta-chain. The goal of the second phase of this project is to continue development of an enzyme linked immunoassay for zeta-globin chains using the monoclonal antibodies developed in the first phase. The prototype assay will be optimized. Clinical samples will be assayed for zeta-containing hemoglobin by the optimized assay and by HPLC. Hematological characteristics of these samples will be measured. Specific gene deletions of some of the samples will also be determined. These data will be used to demonstrate the usefulness of the assay for screening adult populations for alpha-thalassemia-1. A second potential screening assay for zeta-chain containing red blood cells will be developed. An anti-zeta-chain monoclonal antibody is conjugated to fluorescein. This will be used to label zeta globin chains in prepared red blood cells, for the determination of zeta chain containing cells by flow cytometry.

遗传性疾病阿尔法-地中海贫血-1被发现频率最高 在东南亚血统的个体中。而杂合子形式 可能对健康没有不良影响，除了轻微的贫血， 纯合子情况(称为胎儿积水)会导致胎儿死亡。那里 目前还没有现成的临床方法来筛查成年人的这一特征。 然而，有报道称，α-地中海贫血-1的携带者 基因会产生少量的胚胎血红蛋白Zeta链。 该项目第二阶段的目标是继续开发 Zeta-珠蛋白链的单抗酶联免疫分析 抗体形成于第一阶段。 将对原型检测进行优化。临床样本将被化验 用优化的方法和高效液相色谱法测定含Zeta的血红蛋白。 这些样本的血液学特征将被测量。特定的 一些样本的基因缺失也将被确定。这些数据 将被用来证明化验在筛查中的有效性 阿尔法-地中海贫血-1的成年人群。 含红血Zeta链的二次潜在筛选试验 细胞将被开发出来。一种抗Zeta链的单抗 与荧光素结合。这将被用来标记Zeta珠蛋白链 在准备好的红细胞中，用于测定Zeta链 流式细胞仪检测含细胞。