MOLECULAR GENETICS OF INHERITED NEUROLOGIC AND PSYCHIATRIC DISORDERS

我们研究了突变的特征 遗传性神经或精神疾病的研究， 基因组织的特定蛋白质，可能有一个作用， 临床表现的发病机制。 使用 遗传性溶酶体贮积症、戈谢病和法布里病 疾病，作为模型，我们证明，表型 在这些遗传性疾病中看到的异质性是一种 不同突变的结果，每种突变都影响蛋白质 活动和影响加工， 和/或蛋白质的稳定性。 类似的方法也在使用 为了研究II号染色体的基因参与 躁狂抑郁症和其他精神疾病。 重组 DNA技术已被用来阐明的结构， 参与这些蛋白质（酶和受体）的基因 和其他神经精神疾病。 限制性片段长度 已经鉴定了多态性（RFLPs），其可用于 戈谢病中的突变的鉴定， 发生在非神经病和神经病表型中。 北方印迹分析提供了结构的进一步细节， 正常基因和突变基因 分子机制导致 神经系统参与这些疾病也被 研究了 这项研究的结果应该提供一个更多的 诊断和制定的合理基础 这些遗传性疾病的治疗策略。 基因对 对神经递质生物合成有特异性的11号染色体 已经分离（例如，人酪氨酸羟化酶和 色氨酸羟化酶）。 正常基因序列与 阿米什躁狂抑郁症患者的基因序列是 中求进工作总 重组DNA方法已被用于 产生大量酪氨酸羟化酶同工酶， 结构和生物化学研究。

We approached the characterization of the mutations responsible for inherited neurological or psychiatric disorders by studying the gene organization of specific proteins that might have a role in the pathogenesis of the clinical manifestations. Using the inherited lysosomal storage disorders, Gaucher disease and Fabry disease, as models, we demonstrated that the phenotypic heterogeneity seen within these inherited disorders is a consequence of different mutations, each affecting protein activity and influencing the processing, compartmentalization and/or stability of the protein. Similar approaches are being used to investigate the involvement of genes of chromosome II in mania-depression and other psychiatric disorders. Recombinant DNA techniques have been used to elucidate the structure of the gene for the proteins (enzymes and receptors) involved in these and other neuropsychiatric disorders. Restriction fragment length polymorphisms (RFLPs) have been identified that are useful for the identification of mutations in Gaucher disease that frequently occur in both non-neuronopathic and neuronopathic phenotypes. Northern blot analysis provides further details of the structure of the normal and mutant genes. The molecular mechanisms leading to nervous system involvement in these disorders have also been investigated. The results of this research should provide a more rational foundation for the diagnosis and formulation of therapeutic strategies for these inherited disorders. Genes on chromosome 11 specific for neurotransmitter biosynthesis have been isolated (for example, human tyrosine hydroxylase and tryptophan hydroxylase). Comparison of normal gene sequence to the gene sequence in Amish manic-depressive patients is in progress. Recombinant DNA approaches have been used to produce large amounts of tyrosine hydroxylase isozyme for structural and biochemical studies.