HEME AND GLOBIN SYNTHESIS IN INFANTS AND CHILDREN

地中海贫血和镰状细胞病是重要的红细胞 由于人类血红蛋白的遗传缺陷而引起的疾病。 的 该研究项目的目的是调查 血红蛋白病使用各种方法与最终 目的是将研究结果应用于受影响患者的护理。 在 近年来，研究强调了 分子生物学方法对遗传多样性的评价 地中海贫血和其他血红蛋白病， 正常和异常人类珠蛋白表达的控制 基因. 在过去的几年里， 研究的目的是为了分离克隆， 在巨核细胞中表达的蛋白质，包括PF 4、GPIIb和 GPIIIa，以检查造血分化和遗传 血小板的缺陷。 拟议的研究包括检查地中海贫血变体， 从胎儿到成人发育转换的研究 血红蛋白，参与表达的DNA序列分析 血小板蛋白的基因，并阐明了 来自不同种族的血栓无力症患者的缺陷 背景 地中海贫血变体的研究将包括 在珠蛋白基因簇的缺失，一个延续 对β地中海贫血沉默携带者的调查，以及其他 特别是来自近东的突变。 研究 发育转换将涉及DNA的变异 影响两个正常伽马的表达的序列 珠蛋白基因座 巨核细胞基因表达的研究 包括GPIIb、GPIIIa和PF 4的结构分析 基因克隆 血栓无力症患者，出血 GPIIb-GPIIIa血小板缺陷性疾病 结合纤维蛋白原和其他粘合剂的膜复合物 蛋白质，从各种种族背景将在研究 为了澄清DNA中的确切突变， 疾病 拟议的研究应提供以下方面的进一步资料： 由于基因突变引起的疾病， 特异性造血细胞谱系，如地中海贫血、镰状细胞 细胞疾病和血小板无力症。

Thalassemia and sickle cell disease are important red cell disorders due to inherited deficiencies in human hemoglobins. The objective of this research project has been to investigate hemoglobinopathies using a variety of methods with the ultimate aim of applying the findings to the care of affected patients. In recent years, the studies have emphasized applications of molecular biology to the evaluation of the genetic diversity of thalassemia and other hemoglobinopathies and to the examination of the control of expression of normal and abnormal human globin genes. In the past few years, an additional direction for investigation has arisen from the desire to isolate clones for proteins expressed in megakaryocytes, including PF4, GPIIb and GPIIIa, to examine hematopoietic differentiation and genetic defects of platelets. The studies proposed include examination of thalassemia variants, investigation of the developmental switch from fetal to adult hemoglobin, analysis of DNA sequences involved in expression of genes for platelet proteins, and an elucidation of molecular defects in patients with thrombasthenia from a variety of ethnic backgrounds. The studies of thalassemia variants will include deletions in the globin gene clusters, a continuation of the investigation of the silent carrier of beta thalassemia, and other mutations, particularly those from the Near East. Research on the developmental switch will involve variations in DNA sequences that affect the expression of the two normal gamma globin loci. Studies of gene expression in megakaryocytes will include analysis of the structure of GPIIb, GPIIIa, and PF4 genomic clones. Patients with thrombasthenia, a bleeding disorder due to deficiencies in the GPIIb-GPIIIa platelet membrane complex that binds fibrinogen and other adhesive proteins, from a variety of ethnic backgrounds will be studied in order to clarify the exact mutations in DNA responsible for this disease. The proposed studies should provide further information about diseases due to mutations in genes that are characteristic of specific hematopoietic cell lineages such as thalassemia, sickle cell disease, and thrombasthenia.