AN APPROACH TO HUMAN DEVELOPMENT WITH CELL HYBRIDS

人的发展是许多个体生化过程的总和 过程，每一个基因编程系统地发挥作用，导致 酶或蛋白质的最终表达。 某些遗传性 与发育异常相关的溶酶体酶疾病提供了 研究人类酶遗传控制的极好模型 表达和细胞定位。 两个群体的分子遗传学 独特的溶酶体酶紊乱的研究。 他们是 粘脂沉积症和芳基硫酸酯酶-A缺乏症。 遗传 变异表明，多个基因的结构，加工， 对于这两个组改变其它功能。 粘脂剂包括 以G1 cNAc-P转移酶缺乏为特征的粘脂病II型和III型 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个基因参与G1 cNAc-P 转移酶表达 芳基硫酸酯酶-A缺乏症包括 异染性脑白质营养不良，多发性硫酸酯酶缺乏症 疾病，假性缺乏症和激活剂缺乏症 disorder. 芳基硫酸酯酶-A也缺乏粘脂。 有证据表明，可能有4个基因参与了 芳基硫酸酯酶A 体细胞遗传学研究将确定参与基因 粘脂沉积症和芳基硫酸酯酶-A缺乏症。 生物化学， 免疫学和分子研究将表征每个基因。 证据 表明了几种类型的基因，包括结构和加工 基因. 将纯化G1 cNAc-P转移酶和芳基硫酸酯酶-A， 抗体制造 G1 cNAc-P转移酶和芳基硫酸酯酶-A结构基因 将使用不同的替代品进行克隆。 克隆的探针将 用于确定基因组织;疾病相关病变;以及 结构和非结构基因变体的基因表达。 的 生物化学、免疫学和分子标记，包括DNA 多态性，生产将可用于遗传咨询， 人群筛查、基因定位和诊断。 这些研究将 描述了参与溶酶体酶表达的基因， 为人类发展和遗传学提供基本信息。

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.