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。 由于人类血红蛋白遗传缺陷而引起的疾病。这个 这项研究项目的目的一直是调查 使用多种方法治疗血红蛋白疾病，最终 目的将研究结果应用于受影响患者的护理。在……里面 近年来，这些研究都强调了它的应用 以分子生物学为基础的遗传多样性评价方法 地中海贫血和其他血红蛋白疾病的检查 控制正常和异常人珠蛋白的表达 基因。在过去的几年里，另一个方向是 对克隆进行分离的愿望引发了一项调查 巨核细胞表达的蛋白质，包括PF4、GPIIb和 GPIIIa，用于检测造血分化和遗传学 血小板缺陷。 建议的研究包括地中海贫血变种的检查， 胎儿向成人发育转换的研究 血红蛋白，参与表达的DNA序列的分析 血小板蛋白基因及分子生物学研究进展 不同民族血栓性贫血患者的缺陷 背景。地中海贫血变异的研究将包括 珠蛋白基因簇中的缺失，是 β地中海贫血等无症状携带者的调查 突变，特别是来自近东的突变。研究与实践 发育转换将涉及DNA的变异 影响两个正态伽马的表达的序列 珠蛋白基因。巨核细胞基因表达的研究将 包括对GPIIb、GPIIIa和PF4结构的分析 基因组克隆。出现血栓减少、出血的患者 GPIIb-GPIIa血小板缺陷所致的疾病 结合纤维蛋白原和其他粘合剂的膜复合体 来自不同种族背景的蛋白质将在 为了弄清导致这一现象的DNA的确切突变 疾病。 拟议的研究应提供关于以下方面的进一步信息 由基因突变引起的疾病，这些基因具有 特定的造血细胞系，如地中海贫血、镰刀状贫血 细胞疾病和血栓减少症。

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.