AN APPROACH TO HUMAN DEVELOPMENT WITH CELL HYBRIDS

人的发展是许多个体生物化学的总和 过程，每个过程都经过基因编程，系统地发挥作用，领先于 酶或蛋白质的最终表达。某些继承的 与发育异常相关的溶酶体酶病提供 研究人类酶基因控制的优秀模型 表达和细胞定位。两个群体的分子遗传学 将对独特的溶酶体酶病进行研究。他们是 粘脂病和芳基硫酸酯-A缺乏症。遗传 变异表明，具有结构、加工和 两组的其他功能都发生了改变。粘脂病包括 以G1cNAc-P转移酶缺乏为特征的粘脂病II和III 这会影响许多溶酶体酶的生物合成和定位。 我们已经确定了至少3个与G1cNAc-P有关的基因 转移酶的表达。芳基硫酸酯-A缺乏症包括 异色性脑白质营养不良，多重硫酸酶缺乏症 失调症、假性缺乏症和激活剂缺乏 无序。在粘脂病中，芳基硫酸酯-A也是缺乏的。 有证据表明，可能有4个基因参与了 芳基硫酸盐酶-A。 体细胞遗传学研究将确定参与 粘脂病和芳基硫酸酯-A缺乏症。生化的， 免疫学和分子研究将确定每个基因的特征。证据 表示几种类型的基因，包括结构和加工 基因。G1cNAc-P转移酶和芳基硫酸酯酶-A将被提纯并 产生抗体。G1cNAc-P转移酶和芳基硫酸酯酶-A结构基因 将使用不同的替代方案进行克隆。克隆的探针将被 用于确定基因组织；与疾病相关的损伤；以及 基因在结构和非结构基因变体中的表达。这个 生化、免疫学和分子标记，包括DNA 产生的多态将可用于遗传咨询， 人口筛选、基因图谱和诊断。这些研究将 描述参与溶酶体酶表达的基因，它将 为人类发展和遗传学贡献基本信息。

Human development is the summation of many individual biochemical processes, each genetically programed to function systematically, leading to the final expression of an enzyme or protein. Certain inherited lysosomal enzyme disorders associated with abnormal development provide excellent models for studying the genetic control of human enzyme expression and cellular localization. The molecular genetics of two groups of unique lysosomal enzyme disorders will be studied. They are the mucolipidoses and the arylsulfatase-A deficiency disorders. Genetic variants indicate that multiple genes with structural, processing, and other functions are altered for both groups. The mucolipidoses consist of mucolipidosis II and III characterized by a G1cNAc-P transferase deficiency that affects the biosynthesis and localization of many lysosomal enzymes. We have identified at least 3 genes that are involved in G1cNAc-P transferase expression. The arylsulfatase-A deficiency disorders consist of metachromatic leukodystrophy, the multiple sulfatase deficiency disorder, the pseudo deficiency disorder, and the activator deficient disorder. Arylsulfatase-A is also deficient in the mucolipidoses. Evidence suggests perhaps 4 genes involved in the expression of arylsulfatase-A. Somatic cell genetic studies will identify the genes involved in the mucolipidoses and the arylsulfatase-A deficiency disorders. Biochemical, immunological, and molecular studies will characterize each gene. Evidence indicates several types of genes, including structural and processing genes. G1cNAc-P transferase and arylsulfatase-A will be purified and antibodies made. G1cNAc-P transferase and arylsulfatase-A structural genes will be cloned using different alternatives. The cloned probes will be used to determine gene organization; the disease-associated lesions; and gene expression in structural and non-structural gene variants. The biochemical, immunological, and molecular markers, including DNA polymorphisms, produced will be available for genetic counseling, population screening, gene mapping, and diagnosis. These studies will describe genes involved in the expression of lysosomal enzymes, which will contribute basic information for human development and genetics.