GENOTYPIC AND PHENOTYPIC STUDIES OF BIPOLAR DISORDER

这个建议是为了职业发展奖， 候选人继续研究联系战略， 与双相情感障碍（BP）相关的基因， 与BP易感基因相关的表型。该奖项 将为候选人提供支持，因为他发展了以下方面的专业知识： 所需的方法和统计方法 这些项目。主要导师将是纳尔逊弗雷默博士，在 他在加州大学旧金山分校的实验室里， 项目正在进行中。在此期间应学习的方法 包括使用自动化技术进行基因组筛选 和统计学方法来识别与 孤立人群中的双相情感障碍Lodewijk Sandkuiijl博士 将作为一个合作者开发统计方法， 连锁不平衡分析这些数据的来源 研究将从BP的谱系研究中抽取样本， BP的单独连锁不平衡研究，均选自 孤立的哥斯达黎加人严重BP的高危单倍型 已经在许多这些主题中得到了确认， 候选人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，如药物和酒精的使用， 在来自系谱研究的受试者和 BP连锁不平衡研究在这之后的阶段， 建议，从BP患者样本中提取DNA， 弗朗西斯科地区的诊所作为研究的来源 可能首先在哥斯达黎加人中发现的突变 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.