MOLECULAR GENETICS OF INHERITED NEUROLOGIC AND PSYCHIATRIC DISORDERS

我们正在寻找与神经学有关的基因 和精神障碍，特别强调双相情感障碍 情感障碍和精神分裂症。临床表现的异质性 这些遗传性疾病很可能是由于环境 基因的影响和突变(多因素)。分子 技术被用来识别可能预测 不同表型及其分子机制的研究 导致神经系统异常。我们已经隔离了 特征性基因，如神经递质生物合成 人酪氨酸羟基酶和色氨酸羟基酶， 这可能与神经精神障碍有关。vbl.使用 限制性片段长度多态(RFLP)和 微卫星DNA标记，我们正在对来自 情感障碍风险高的大家庭中的个人 我们正在进行连锁分析，以确定 含有易感基因或保护性基因的染色体区域 参与双相情感障碍(见项目#Z01，MH 02625-07海南)。对于已识别的染色体区域 表达的序列将被分离和鉴定。人类 含有三核苷酸重复序列的基因组DNA正在被分离和 特色化的。我们发现了一个三核苷酸重复序列 染色体17q，它解释了由 重复扩增检测(RED)技术。细胞遗传学研究， 包括荧光原位杂交(FISH) 受双相情感障碍、精神分裂症影响的个人 (特别是儿童时期的发病，见项目#MH-02581-07，卫生与公众服务部)， 智力低下、自闭症和注意缺陷多动 多动症(ADHD)，正在进行染色体鉴定 可能有助于识别疾病基因的异常。我们 已发现染色体22q11.2间隙缺失 儿童期起病的精神分裂症患者，以及与 X染色体十二聚体插入变异等位基因与精神疾病 智力迟缓。这项研究的结果应该提供一个分子 诊断和开发新疗法的基础 针对这些障碍的策略。

We are searching for genes involved in neurologic and psychiatric disorders, with a particular emphasis on bipolar affective disorder and schizophrenia. The clinical heterogeneity seen within these inherited disorders is likely due to environmental influences as well as mutations in genes (multifactorial). Molecular techniques are used to identify mutations that may be predictive of different phenotypes and to understand the molecular mechanisms leading to nervous system abnormalities. We have isolated and characterized genes, such as the neurotransmitter biosynthetic enzymes human tyrosine hydroxylase and tryptophan hydroxylase, that may be involved in neuropsychiatric disorders. Using restriction length fragment polymorphisms (RFLP) and microsatellite DNA markers, we are genotyping DNA from individuals in large families where there is a high risk for affective disorder and we are performing linkage analysis in order to identify chromosome regions harboring susceptibility or protective genes involved in bipolar affective disorder (see Project #Z01 MH 02625-07 NS). For the chromosome regions that are identified expressed sequences will be isolated and characterized. Human genomic DNA containing trinucleotide repeats is being isolated and characterized. We have found a trinucleotide repeat on chromosome 17q that accounts for most expansions detected by the Repeat-Expansion Detection (RED) technique. Cytogenetic studies, including fluorescent in-situ hybridization (FISH), on cells from individuals affected with bipolar affective disorder, schizophrenia (particularly childhood onset, see Project #MH-02581-07 CHP), mental retardation, autism, and attention deficit hyperactivity disorder (ADHD), are being performed to identify chromosomal abnormalities that may aid in the identification of disease genes. We have identified chromosome 22q11.2 interstitial deletions among childhood onset schizophrenics, and also the association of an X-chromosome dodecamer insertional variant allele with mental retardation. The results of this research should provide a molecular basis for diagnosis and for the development of novel therapeutic strategies for these disorders.