Schizophrenia Susceptibility Genes

描述(申请人提供)：精神分裂症是一种常见的致残性疾病，具有不同的表现和未知的病因，大多数病例在45岁之前发病。认知和情绪障碍都会导致社会和职业损害。有令人信服的证据表明，遗传易感性在决定谁受到影响方面发挥了一定作用。像大多数常见的复杂疾病一样，几个或多个不同基因座的突变很可能与易感性有关。自1983年以来，我们小组一直专注于精神分裂症和其他精神障碍的流行病学和遗传学研究。我们已经开发了几个临床样本，包括精神分裂症的多个家系。对这些家系进行了一系列调查，包括连锁研究，这些研究提供了8号、13号和22号染色体上精神分裂症易感基因的证据。其他团体也支持这些发现。这些家庭中的个人最后一次露面是在1989-1995年期间。毫无疑问，这些家庭中有一些人后来患上了精神分裂症。这项研究的长期目标是定位和表征与精神分裂症有关的重要基因，并检验某些遗传决定的易感性与患者可识别的亚群有关的假设。这项申请请求支持更新我们已经建立的大型多基因家族中个体的临床状态，补充我们来自淋巴母细胞系的DNA供应，并对以前获得的分子数据以及将在此赠款期间产生的新数据进行最先进的分析(即，使用高度多态的微卫星标记和匿名和候选SNP进行连锁分析、连锁不平衡研究和单倍型相对风险研究)。这项分子遗传学实验室工作不需要任何支持。在最初的赠款期间，实验室的工作将集中在识别8号染色体上的易感基因。了解导致精神分裂症的因素可能使受影响的个人及其亲属受益，识别相关基因可能为开发改善这些疾病的药物提供新的靶点。

DESCRIPTION (provided by applicant): Schizophrenia is a frequent and disabling disease of variable expression and unknown etiology, with the majority of cases having an onset before age 45. Both cognitive and emotional dysfunction is observed causing social and occupational impairment. There is convincing evidence that genetic susceptibility plays some role in determining who is affected. Like most common complex diseases, it is likely that mutations at several or many different loci are associated with susceptibility.Since 1983 our group has focused on the epidemiologic and genetic study of schizophrenia and other psychotic disorders. We have developed several clinical samples including multiplex pedigrees with schizophrenia. These families have been examined in a series of investigations including linkage studies that have provided evidence for schizophrenia susceptibility loci on chromosomes 8, 13 and 22. Other groups have supported these findings. Individuals in these families were last seen during the period 1989-1995. There are undoubtedly individuals in these families who have since developed schizophrenia.The long term objective of this research is to localize and characterize genes of importance to schizophrenia and to test the hypothesis that some genetically-determined susceptibility is associated with identifiable subgroups of the patients. This application requests support to update the clinical status of individuals in our large, already-established multiplex families, to replenish our supply of DNA from lymphoblastoid cell lines and to conduct state of the art analyses of previously obtained molecular data as well as the new data that will be generated during this grant period (i.e., linkage analysis, linkage disequilibrium studies, and haplotype relative risk studies, using highly polymorphic microsatellite markers and anonymous and candidate SNP's). No support is necessary for this molecular genetics laboratory work. For this initial grant period, laboratory efforts will focus on identifying a susceptibility gene on chromosome 8. Understanding the factors that contribute to schizophrenia may benefit affected individuals and their relatives, Identification of the genes involved may provide new targets for the development of medications to ameliorate these disorders.