GENOTYPIC AND PHENOTYPIC STUDIES OF BIPOLAR DISORDER

这项提议是为了设立职业发展奖，让 候选人将继续他的连锁战略研究以定位 与双相情感障碍(BP)相关的基因和更好地定义 与BP易感基因相关的表型(S)。获奖名单 将为候选人提供支持，帮助他在以下方面发展专长 必须采用的方法和统计方法 这些项目。主要导师将是纳尔逊·弗莱默博士， 其在加州大学旧金山分校的实验室进行了多个连锁和定位克隆 项目目前正在进行中。在此过程中需要学习的方法 期间包括使用自动化技术进行基因组筛选 和统计方法来识别与 与世隔绝人群中的双相情感障碍。洛德维克·桑德奎尔博士 将作为开发统计方法的合作者 连锁不平衡分析。这些数据的来源 研究将从BP和A的系谱研究中提取样本 BP的分离连锁不平衡研究，均选自 与世隔绝的哥斯达黎加人重症BP的高危单倍型 已经在许多这样的主题中被发现，并且 应聘者将学习精细绘图和突变分析的技能 使用这些样本。可能与之相互作用的环境因素 BP的病程和严重程度，如吸毒和酗酒，将 在两个主题中进行评估，来自系谱研究和 BP的连锁不平衡研究。在这个过程的后期阶段 提议，从BP患者样本中提取DNA将从 旧金山地区的诊所作为研究的来源 在哥斯达黎加人中可能最先发现的突变 人口。

This proposal is for a career development award to allow the candidate to continue his studies Of linkage strategies to locate genes associated with bipolar disorder (BP) and to better define the phenotype(s) associated with BP predisposition genes. The award will provide support for the candidate as he develops expertise in the methodology and statistical apprOaches necessary to pursue these projects. The principal mentOr will be Dr. Nelson Freimer, in whose laboratory at UCSF several linkage and positional cloning projects are now underway. Methodologies to be learned during this periOd include the use Of autOmated technOlogy for genome screening and statistical approaches to identifying genes associated with bipolar disorder in isolated populations. Dr. Lodewijk Sandkuiijl will serve as a collaborator on developing statistical methods for linkage disequilibrium analysis. The source of the data for these studies will be samples drawn from pedigree studies of BP and a separate linkage disequilibrium study of BP, both selected from the isolated Costa Rican population. High risk haplotypes for severe BP have already been identified in many of these subjects, and the candidate will learn skills for fine mapping and mutation analysis using these samples. Environmental factors which may interact with the course and severity of BP, such as drug and alcohol use, will be evaluated in both subjects from the pedigree studies and the linkage disequilibrium studies of BP. In the latter stages of this proposal, DNA from a sample of BP patients will be drawn from clinics in the San Francisco area to serve as a source for studying mutations that may be identified first in the Costa Rican population.