PHASE II COOPERATIVE AGREEMENT FOR GENETICS STUDIES

此申请是对RFA MH 94-10“第二阶段合作”的响应 《双相情感障碍和精神分裂症遗传学研究协议》。 在阶段1期间，称为“诊断中心” 精神病学关联研究，临床数据和DNA(包括细胞 线路)已在四个中心使用共同协议收集。一个 总共有140个家庭至少有两个躁郁症先证者 收好了。 这一建议的目的是识别与家族性心脏病相关的基因。 双相情感障碍。正在进行的合作将按顺序扩展 对第一阶段收集的家系进行基因分型并进行连锁 分析。在第二阶段，四个中心将继续分工 同样如此。 我们将采用三阶段法进行基因分型。在舞台上，L 基因组调查将在一个小组上以7厘米摩根的间隔进行 在524名有双相表型或需要的受试者中 建立阶段。选择此面板是为了最大限度地发挥优势 受影响的同胞对和受影响的系谱成员方法。 还将使用参数(LOD-SCORE)方法。阶段II面板 将包括在阶段I之后收集的新族。使用此 更强大的样本，基于阶段的感兴趣的染色体区域 L的调查结果和实地报告将得到跟踪。 在第三阶段，样本将扩大到包括 复发性单相情感障碍。将对以下对象执行LOD-Score分析 这个扩大的家系样本的目标是遵循有希望的 第一阶段和第二阶段的调查结果。 我们将对我们的血统进行模拟，以确定大多数 强大的连锁性和异质性测试分析方法。 此外，我们还将利用丰富的临床数据集，以便 测试对这种复杂表型的各种定义。 最后，我们将开发一个档案数据库，供科学工作者使用 UO1合同中详细说明的社区。

This application is a response to RFA MH 94-10 "Phase Two Cooperative Agreement for Genetic Studies of Bipolar Disorder and Schizophrenia." During Phase 1, known as "Diagnostic Centers for Psychiatric Linkage Studies," clinical data and DNA (including cell lines) have been collected at four centers using a common protocol. A total of 140 families with at least two bipolar I probands have been collected. The purpose of this proposal is to identify genes involved in familial bipolar disorder. The ongoing collaboration will be extended in order to genotype the families collected in Phase 1 and perform linkage analyses. In Phase 2, the four centers will continue to divide the work equally. We will employ a three stage approach to genotyping. In Stage l a genomic survey will be performed at 7 centiMorgan intervals on a panel of 524 subjects who have bipolar phenotypes or who are needed to establish phase. This panel has been selected to take maximal advantage of the affected sib-pair and affected pedigree member methods. Parametric (LOD-score) methods will also be used.The Stage II panel will include new families that were collected after Stage I. Using this more powerful sample, chromosomal regions of interest based on Stage l findings and reports from the field will be followed up. In Stage III, the sample will be expanded to include subjects' with recurrent unipolar disorder. LOD-score analyses will be performed on this sample of enlarged pedigrees with the goal of following promising findings from stages I and II. We will perform simulations of our pedigrees to determine the most powerful analytical methods of testing for linkage and heterogeneity. In addition, we will utilize the rich clinical data set in order to test various definitions of this complex phenotype. Finally, we will develop an archival database for use by the scientific community as detailed in the U O1 contracts.