GENETICS OF HUMAN DEVELOPMENT AND METABOLIC DISEASE

人的发展是个体生物化学的总和 过程，每个过程都经过基因编程，在系统中发挥作用 途径，导致酶的最终表达和定位 或者蛋白质。一种酶的发展和定位 需要几个基因，这些基因起着加工、时间、 作用于结构上的建筑、靶向和受体基因 基因产物。遗传性溶酶体酶病相关 为非正常发展提供了极好的模式 研究不同数量和类型的基因所需的 一种酶的发展。这项研究旨在剖析， 识别和表征几个新的基因，这些基因是 最终实现了一种溶酶体酶。要做到这一点，2 将研究几组溶酶体酶病： 粘脂病和芳基硫酸酯酶A缺乏症。每个人 涉及几个受影响的基因，所有这些都是 一种溶酶体酶的开发。粘脂病(ML) 由MLII和MLIII组成，以高尔基GlcNAc-P- 转移酶(GNPT)缺乏影响生物合成和 溶酶体酶的定位。我们已经确认了至少3个 所需的基因。芳基硫酸酯-A缺乏症 由异色性脑白质营养不良、多种硫酸酯酶组成 虚证、假性虚证和 激活剂缺乏症。芳基硫酸酯酶-A也缺乏 粘脂病。我们的证据表明至少有10个基因 参与芳基硫酸酯酶-A(ARSA)的最终表达。 因此，这项研究有可能解剖和 确定了至少10个参与这一过程的新基因， 溶酶体酶的靶向和发展，总的来说，和 特别是ARSA。 体细胞研究将从基因上解剖和鉴定 基因。遗传学、生化、免疫学和分子生物学 有人建议进行研究，以确定这些基因和酶的特征。 已确定粘脂病基因连锁的大家族 学习。我们的证据表明有几种类型的基因，包括 结构、加工、靶向、时间和受体。克隆的 基因将被用来描述GNPT的组织、疾病- 相关突变体和基因表达。所有标记物都显影了 将可用于遗传咨询，人口筛查， 基因图谱和诊断。这些研究将描述所涉及的 在溶酶体酶的表达、加工和靶向过程中， 这将为人类发展提供基本信息 以及遗传学和溶酶体的生物合成。

Human development is the summation of individual biochemical processes, each genetically programed to function in a systematic way, leading to the final expression and localization of an enzyme or protein. The development and localization of an enzyme require several genes which function as processing, temporal, architectural, targeting and receptor genes acting on a structural gene product. Inherited lysosomal enzyme disorders associated with abnormal development provided excellent models for studying the different numbers and types of genes required for the development of an enzyme. This study is designed to dissect, identify and characterize several new genes necessary for the final realization of a lysosomal enzyme. To accomplish this, 2 sets of lysosomal enzyme disorders will be studied: the mucolipidoses and the arylsulfatase A deficiency disorders. Each involve several affected gene all of which are required for the development of a lysosomal enzyme. The mucolipidoses (ML) consist of MLII and MLIII characterized by the golgi GlcNAc-P- transferase (GNPT) deficiency affecting the biosynthesis and localization of lysosomal enzymes. We have identified at least 3 genes that are required. 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. Our evidence suggests at least 10 genes involved in the final expression of arylsulfatase-A (ARSA). Therefore, this study has the potential of dissecting and identifying at least 10 new genes involved in the processing, targeting and development of lysosomal enzymes, in general, and ARSA, in particular. Somatic cell studies will genetically dissect and identify the genes. Genetic, biochemical, immunological, and molecular studies are proposed to characterize the genes and enzymes. Large families have been identified for mucolipidosis gene linkage studies. Our evidence indicates several types of genes, including structural, processing, targeting, temporal and receptor. Cloned genes will be used to characterize GNPT organization, disease- associated mutants, and gene expression. All markers developed will be available for genetic counseling, population screening, gene mapping, and diagnosis. These studies will describe involved in the expression, processing, and targeting of lysosomal enzymes, which will contribute basic information for human development and genetics and the biosynthesis of the lysosome.