A thyroid receptor co-activator hypothesis for psychosis

描述：（由申请人提供）精神分裂症是一种神经发育障碍， 这种综合征影响了大约1%的美国人口， 以出现幻觉和妄想为特征。遗传因素 被认为是大多数易患病的原因， 这种综合症。这些遗传因素被认为是由主要的， 中度和轻度效应位点。的鉴定和表征 即使是温和的影响基因座的遗传因素是一个关键步骤的过程中， 了解这组疾病的发病机制。 在先前的分子研究中，候选人已经确定了外显子多态性 （HOPA 12 bP）在甲状腺受体辅激活剂基因的关键部分 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症在这五年的培训补助金中， 候选人建议专注于与以下相关的行为综合征： 多态性和1）证明多态性的分离， 病2.细化与多态性相关的表型，以及3） 识别可能与疾病有关的其他突变。 该基金的科学目的是1）。进行病例对照分析 HOPA 12 bp多态性的精神分裂症先证者。精神分裂症HOPA 将识别先证者并与匹配的病例对照进行比较， 认知/行为、内分泌和医学差异。2.进行 HOPA 12 bp先证者家族的集中连锁研究。结构化 访谈将用于评估认知/行为和 对照组和HOPA组一级亲属的医学共病12 bP 先证者这些结果将与遗传状态相关。3）。进行 通过HOPA基因的SSCP分析检测其他潜在致病性 突变。突变分析将使用来自其他组织的DNA进行。 精神分裂症患者检测HOPA基因的其他突变， 导致该综合征或相关表型。 该补助金的培训目的是：1）发展诊断方面的临床技能 复杂行为和内分泌的标准化测量 疾病，和2）学习医学和精神病学流行病学，伦理学， 复杂疾病的生物统计学方法净效应将是 培养一名独立的调查员，能够进行功能和翻译 research.

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.