Admixture Mapping Schizophrenia Genes in Oceanic Palau

描述(申请人？S摘要)：精神分裂症是一种毁灭性的精神疾病 造成数不清的痛苦和损失的综合症。尽管文化不同 和世界各地的环境，流行和呈现 全世界的精神分裂症都是相似的。它的介绍和课程都不是 在帕劳偏远的海洋人口中不同，但人口 帕劳的结构为探索基因提供了独特的机会 这种毁灭性疾病的病原学。特别是，帕劳的人口是 起源于最近，大约比现在早2000年(BP)；帕劳有 至少经历了两个实质性的瓶颈，在成立时和最近由于 由欧洲/美国接触者引起的疾病(约200个基点)； 人口在其历史上经历了较小的有效人口 比大多数现代社会都大；帕劳显然经历了广泛的 男性偏向的基因流动。所有这些元素结合在一起就产生了联系 常染色体和X染色体上等位基因间的不平衡(LD)，即 即使在染色体上很远的距离也能检测到。 我们的主要目标是找出致病基因 通过使用帕劳的特殊功能来治疗精神分裂症。除了它独一无二的 人口遗传学，帕劳精神分裂症的发病率略有上升，为2.77 男性为1.24%，女性为0.5%至1% 全球性平均率。有156个？在岛上？精神分裂症患者，其中 有154人贡献了DNA。此外，我们还抽样了495名关键亲属。因此， 这个项目不需要招聘。相反，我们可以专注于联系 和LD分析以绘制易感基因图谱。对于前者，扩展的谱系和 有可用的连锁工具；只有额外的基因分型和分析 必填项。对于后者，我们提出了基于链接的LD分析 结果和全基因组扫描，这使用了一个粗略的标记网格。我们的 初步结果证实，这两种方法都有可能取得成功。统计 将开发方法来补充LD的分子分析 本研究的组成部分。 此申请是作为两个站点的协作角色提交的 临床研究或精神障碍的机制。合作网站有 匹兹堡大学(德夫林)、卡内基梅隆大学(罗德， 转包给皮特)和加州大学欧文分校(拜尔利)。

DESCRIPTION (Applicant?s Abstract): Schizophrenia is a devastating psychiatric syndrome that causes untold suffering and losses. Despite differing cultures and environments around the world, the prevalence and presentation of schizophrenia worldwide is similar. Its presentation and course are no different in the Remote Oceanic population of Palau, but the population structure of Palau presents unique opportunities to explore the genetic etiology of this devastating illness. In particular, the population of Palau is of recent origin, founded about 2000 years before present (BP); Palau has undergone at least two substantial bottlenecks, at founding and recently due to disease introduced by European/American contact (approximately 200BP); the population has throughout its history experienced smaller effective population size than most modern societies; and Palau has apparently experienced extensive male-biased gene flow. All of these elements combine to generate linkage disequilibrium (LD) among alleles on autosomal and X chromosomes, which is detectable even at substantial distances on chromosomes. Our principal objective is to identify genes that underlie liability to schizophrenia by using the special features of Palau. In addition to its unique population genetics, Palau has a slightly elevated rate of schizophrenia, 2.77 percent in males and 1.24 percent in females, compared to the 0.5 to 1 percent sex-averaged rate worldwide. There are 156 ?on-island? schizophrenics, of whom 154 have contributed DNA. In addition, we have sampled 495 key relatives. Thus no recruitment is required for this project. Instead, we can focus on linkage and LD analyses to map liability genes. For the former, extended pedigrees and linkage tools are available; only additional genotyping and analyses are required. For the latter, we propose LD analyses on the basis of linkage results and a whole genome scan, which uses a coarse grid of markers. Our preliminary results confirm the likely success of both approaches. Statistical methods will be developed to complement the molecular analyses for the LD component of this study. This application is submitted as a two-site, collaborative ROl under the mechanism of the Clinical Studies or Mental Disorders. Collaborating sites are the University of Pittsburgh (Devlin), Carnegie Mellon University (Roeder, subcontract to Pitt) and University of California Irvine (Byerley).