A thyroid receptor co-activator hypothesis for psychosis

描述：(申请人提供)精神分裂症是一种神经发育 一种影响大约1%的美国人口的综合症， 以幻觉和妄想的存在为特征。遗传因素 被认为是疾病易感性的主要原因 这种综合症。这些遗传因素被认为是由主要的， 中度蚂蚁轻度效应基因座。金黄色葡萄球菌的鉴定与表征 即使是轻微效应基因座的遗传因素也是这一过程中的关键一步。 了解这组疾病的发病机制。 在先前的分子生物学研究中，候选基因已鉴定出一种外显子多态 (HOPA12bP)在甲状腺受体辅活化子基因的关键部分 名为HOPA，与行为内表型相关，包括 精神分裂症和甲状腺功能减退。在这笔五年的培训补助金中， 候选人建议将重点放在与 多态和1)表明多态与 生病了。2)提炼与该多态相关的表型；3) 确定其他可能与疾病有关的突变。 这笔赠款的科学目标是1)。某医院门诊就诊病例对照分析 HOPA12bp多态的精神分裂症先证者。精神分裂症患者高收入家庭保障 将确定先证者并将其与匹配的病例对照进行比较 认知/行为、内分泌和医学上的差异。2.开展 HOPA12bp先证者家系的重点连锁研究结构化 访谈将被用来评估认知/行为和 CONTROL和HOPA12bP一级亲属的医学共病 先驱们。这些结果将与遗传状态相关。3)。行为 通过对HOPA基因的SSCP分析来检测其他潜在的致病因素 突变。突变分析将使用来自其他生物的DNA 精神分裂症患者检测HOPA基因的其他突变 导致这种综合征或相关的表型。 这笔赠款的培训目标是：1)发展诊断的临床技能 以及复杂行为和内分泌的标准化测量 2)学习医学和精神病学流行病学、伦理学和 复杂疾病的生物统计学方法。其最终效果将是 培养一名能够发挥职能和翻译能力的独立调查员 研究。

DESCRIPTION: (provided by applicant) Schizophrenia is a neurodevelopmental syndrome that affects approximately 1 percent of the U.S. population and is characterized by the presence of hallucinations and delusions. Genetic factors are thought to account for the majority of the vulnerability to illness for this syndrome. These genetic factors are thought to be composed of major, moderate ant mild effect loci. The identification and characterization of genetic factors of even mild effect loci is a critical step in the process of understanding the pathogenesis of this group of disorders. In prior moleular studies, the candidate has identified an exonic polymorphism (HOPA12bP) in a critical portion of a gene for a thyroid receptor co-activator named HOPAthat is associated with a behavioral endophenotype that include schizophrenia and hypothyroidism. In this five year training grant, the candidate proposes to focus on the behavioral syndrome that is associated with the polymorphism and 1) demonstrate segregation of the polymorphism with illness. 2 refine the phenotype associated with the polymorphism, and 3) identify other mutations that may be related to illness. Scientific Aims of this grant are 1). Peform case control analyses on schizophrenic probands with the HOPA12bp polymorphism. Schizophrenic HOPA probands will be identified and compared to matched case controls for cognitive/behavioral, endocrinological and medical differences. 2. Conduct a focused linkage study of the families of HOPA12bp probands. Structured interviews will be used to assess the presence of cognitive/behavioral and medical co-morbidity in the first-degree relatives of control and HOPA12bP probands. These results will be correlated with genetic status. 3). Conduct SSCP analysis across the HOPA Gene to detect other potentially pathogenic mutations. Mutation analysis will be performed using DNA from other schizophrenic patients to detect other mutations in theHOPA gene that can result in result in this syndrome or related phenotypes. Training Aims of this grant are to 1) develop clinical skills in the diagnosis and standardized measurement of complex behavior and endocrinological disorders, and 2) learn medical and psychiatric epidemiology, ethics, and biostatistical approaches to complex disorders. The net effect will be to produce an independent investigator capable of functional and translational research.