MOLECULAR GENETICS OF BIPOLAR DISORDER

描述：(改编自调查人员摘要)这项提案在 对题为“精神障碍的分子遗传学”的RFA 98-010的回应， 一项基于国家咨询委员会建议的研究计划 精神健康理事会和NIMH遗传学工作组。广泛的目标 建议的研究的目的是检测和定位易感基因 躁郁症及相关的情绪障碍。这一目标将通过一个 在全基因组范围内寻找疾病和标记基因座之间的联系 多胎家系的大样本。调查人员提出了一个两个地点 国际项目是收集系谱样本。具体地说，它 建议(1)收集300个家系的样本，其中包括约400个 受影响的同胞对患有双相I型障碍和60至75个延长的高- 致密家系；(2)临床评估受试者使用DIGES和 Figs访谈，并根据以下内容获得最佳估计临床诊断 面谈、家族史、病历；(3)采集血样 来自信息丰富的主题，用于连锁分析，DNA提取和 建立细胞系；(4)用377进行10 cM基因组扫描 微卫星标记；(5)分析临床和基因分型资料 使用各种统计方法的联系的证据；以及(6)基于 连锁结果，为进一步研究确定候选基因组区域。 将对大约1500名受试者进行研究。调查人员将会做出 向科学界提供临床和生物学数据，以 促进绘制和克隆疾病基因的工作。长期目标 将包括疾病基因的鉴定和特征 使用一系列的分子技术；阐明基因环境， 具有连锁基因的病例的相互作用和特征以确定 并定义疾病的同质子集。这些长期目标 将在续签申请中考虑。 一系列独特的系谱的可获得性，加上最近 诊断程序、分子遗传学技术和 连锁分析方法，是解开遗传机制的好兆头 这是某些形式的双相情感障碍的基础。反过来，这可能会 对病因学、病因学、病理生理学和 可能，预防和治疗这种疾病。

DESCRIPTION: (Adapted from investigator's abstract) This proposal is in response to RFA 98-010 entitled "Molecular Genetics of Mental Disorders," a research initiative based on recommendations of the National Advisory Mental Health Council and the NIMH Genetics Workgroup. The broad objective of the proposed research is to detect and localize susceptibility loci for bipolar and related mood disorders. This goal will be attained through a genome-wide search for linkage between the disease and marker loci in a large sample of multiplex pedigrees. The investigators propose a two-site international project is to collect the pedigree sample. Specifically, it is proposed to (1) collect a sample of 300 pedigrees, including about 400 affected sib pairs with bipolar I disorder and 60 to 75 extended high- density pedigrees; (2) evaluate subjects clinically using the DIGS and FIGS interviews, and obtain best estimate clinical diagnoses based on interview, family history, and medical records; (3) obtain blood samples from subjects informative for linkage analysis, for DNA extraction and creation of cell lines; (4) conduct a 10cM genome scan with 377 microsattelite markers; (5) analyze the clinical and genotypic data for evidence of linkage using various statistical methods; and (6) based on the linkage results, identify candidate genomic regions for further study. About 1,500 subjects will be studied. The investigators will make available to the scientific community the clinical and biological data to facilitate efforts to map and clone the disease genes. Long-term goals will include the identification and characterization of the disease genes using a gamut of molecular techniques; elucidation of gene-environment, interaction, and characterization of cases with linked genes to identify and define homogenous subsets of the disorder. These long-term objectives will be considered in a renewal application. The availability of a unique series of pedigrees, coupled with recent advances in diagnostic procedures, molecular genetics techniques and linkage analysis methods, bode well for unraveling the genetic mechanisms that underlie some forms of bipolar disorder. This, in turn, may have important implications for the etiology, nosology, pathophysiology and, possibly, prevention and treatment of this disorder.