MOLECULAR GENETICS OF INHERITED NEUROLOGIC AND PSYCHIATRIC DISORDERS

我们探讨了导致遗传性突变的特征。 通过研究神经或精神疾病的基因组织 特定的蛋白质可能在致病机制中起作用 临床表现。利用遗传性溶酶体储存障碍， 以高谢病为模型，我们证明了其表型 这些遗传性疾病中出现的异质性是 不同的突变，每个突变都会影响蛋白质的活性并影响 蛋白质的加工、分隔和/或稳定性。南方 分析和聚合酶链扩增用于鉴定突变 在高谢病中，经常发生在非神经病变和 神经病的表型。导致神经紧张的分子机制 对这些疾病的系统参与也进行了调查。这个 本研究的结果将为今后的研究提供更合理的依据。 遗传性骨质疏松症的诊断和治疗策略的制定 精神错乱。类似的方法正在被用来调查 候选基因与双相情感障碍和其他精神疾病的关系 精神错乱。重组DNA技术已被用于识别基因 这可能与神经精神障碍有关。特定于 神经递质生物合成(例如，人酪氨酸羟基酶和 色氨酸羟基酶)和受体(例如，人GABA受体) 已经被隔离了。连锁分析与候选基因鉴定 在阿米什双相情感障碍患者中继续存在。重组DNA表达系统 已经被用来生产大量的大脑蛋白质，用于结构 和生化研究。

We approached the characterization of 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 disorder, Gaucher disease, as a model, 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. Southern analysis and polymerase chain amplification is used to identify mutations in Gaucher disease that frequently occur in both non-neuronopathic and neuronopathic phenotypes. 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. Similar approaches are being used to investigate the involvement of candidate genes in bipolar illness and other psychiatric disorders. Recombinant DNA techniques have been used to identify genes that may be involved in neuropsychiatric disorders. Genes specific for neurotransmitter biosynthesis (for example, human tyrosine hydroxylase and tryptophan hydroxylase) and receptors (for example, human GABA receptor) have been isolated. Linkage analysis and candidate gene identification continues in Amish bipolar patients. Recombinant DNA expression systems have been used to produce large amounts of brain proteins for structural and biochemical studies.