GENETICS OF PSYCHOPHYSIOLOGICAL SCHIZOPHRENIA PHENOTYPES

精神生理性精神分裂症表型的遗传学

基本信息

批准号：
2675194
负责人：
Hilary Coon
金额：
$ 10.45万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-07-01 至 2001-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2675194
关键词：
Pacific Islander behavioral /social science research tag caucasian American clinical research family genetics genetic markers human subject human tissue linkage disequilibriums phenotype psychophysiology racial /ethnic difference restriction fragment length polymorphism schizophrenia sensory feedback smooth pursuit eye movement

项目摘要

DESCRIPTION (Adapted from applicant's abstract): The purpose of this study is to combine information from variables measuring psychophysiological endopheno-types of smooth pursuit eye movement (SPEM), and the P50 evoked auditory response to investigate the genetics of schizophrenia. Studies will be conducted in two unique populations, which will allow us to an underlying quantitative liability to schizophrenia: 1) 14 moderately-sized Utah pedigrees genotyped with over 500 highly informative microsatellite markers, so that a disease gene will map 5 cM or less from a genetic marker. These families have also been phenotyped with P50, and new pilot SPEM data are promising. 2) A sample from an isolated island population in Palau, Micronesia which will include information from all living schizophrenics and their families. Because it is a population isolate, a gene contributing to disease suscept-ibility may be more likely to reside on a single ancestral haplotype. Experiment 1) Variable Selection: Utah Sample. Variables from P50 and SPEM will be examined in the Utah families to determine which abnormalities co-occur with illness, show substantial variability, show abnormalities in unaffected family members, and finally show overlap across phenotypic domains. Experiment 2) Segregation Analysis: Utah Sample. Using the Utah families, the best quantitative measures from experiment 1 will be tested to determine which are the most consistent with sample patterns of transmission. A composite variable including schizophrenia and the endophenotypes will be generated which will represent a quantitative liability for schizophrenia. Experiment 3) Linkage analysis: Utah Sample. Linkage analyses will be performed using the Utah families described above with the quantitative endophenotypes and liability measure. Experiment 4) Normative studies of the endophenotypes in Palau. A sample of 70 Palauan schizophrenics and 70 matched normal controls will be analyzed to determine the phenotypic distribution of SPEM and P50 variables in Palauan subjects. Experiment 5) Application of Experiments 1-3 in the Palau Sample. Analytic strategies developed and tested in the Utah sample in experiments 1-3 will be applied to the Palau sample. Although regions of potential linkage will take priority in the linkage phase of the Palau sample, a genome scan will also be employed as genes for schizophrenia may differ in this ethnic isolate. Experiment 6) Linkage disequilibrium. In the event that a region of linkage is found, they will test for linkage disequilibrium using techniques that have been applied in similar Finnish populations.

描述（改编自申请人的摘要）：本研究的目的是结合来自测量心理生理变量的信息平滑追踪眼动 (SPEM) 的内表型，以及 P50 诱发听觉反应来研究精神分裂症的遗传学。研究将在两个独特的人群中进行，这将使我们能够精神分裂症的潜在数量责任：1) 14 中等规模使用 500 多个信息丰富的微卫星对犹他州谱系进行基因分型标记，以便疾病基因与遗传标记的距离为 5 cM 或更小。这些家族还通过 P50 和新的试点 SPEM 数据进行了表型分析是有希望的。 2) 来自帕劳孤岛种群的样本，密克罗尼西亚将包括所有活着的精神分裂症患者的信息他们的家人。因为它是一个群体分离物，一个基因有助于疾病易感性可能更可能存在于单一祖先身上单倍型。实验1）变量选择：犹他州样本。 P50 和 SPEM 的变量将在犹他州家庭中进行检查以确定哪些异常与疾病同时发生，表现出显着的变异性，表现出异常未受影响的家庭成员，最终显示出表型重叠域。实验 2) 分离分析：犹他州样品。利用犹他州的家庭，将测试实验 1 中的最佳定量测量以确定这与样本传播模式最一致。一个包括精神分裂症和内表型的复合变量将是产生的这将代表精神分裂症的定量责任。实验3）连锁分析：犹他州样本。连锁分析将使用上述犹他州家庭进行定量内表型和责任措施。实验4）帕劳内表型的规范性研究。的样本将分析 70 名帕劳精神分裂症患者和 70 名匹配的正常对照者，以确定帕劳 SPEM 和 P50 变量的表型分布科目。实验5）实验1-3在帕劳样本中的应用。分析型实验 1-3 中在犹他州样本中开发和测试的策略将应用于帕劳样本。尽管潜在联系的区域将优先考虑帕劳样本的连锁阶段，基因组扫描将也被用作精神分裂症的基因在这个种族中可能有所不同隔离。实验6）连锁不平衡。如果链接区域一旦发现，他们将使用以下技术测试连锁不平衡：已应用于类似的芬兰人群。