MOLECULAR GENETICS OF BIPOLAR DISORDER

描述：（改编自研究者摘要）本提案在 对题为“精神障碍的分子遗传学”的RFA 98-010的回应， 根据国家咨询委员会的建议， 精神卫生理事会和NIMH遗传学工作组。其广泛目标 研究的目的是检测和定位 躁郁症和相关的情绪障碍。这一目标将通过一个 全基因组搜索疾病和标记基因座之间的连锁， 多重家系大样本。研究人员提出了一个两个地点 国际项目是收集系谱样本。具体 建议（1）收集300个家系的样本，其中约400个 受影响的同胞对双相I型障碍和60至75扩展高- 密度谱系;（2）使用DIGS临床评估受试者， FIGS采访，并获得最佳估计的临床诊断的基础上， 询问、家族史和医疗记录;（3）获取血液样本 用于连锁分析、DNA提取和 （4）用377个细胞进行10 cM基因组扫描， 微卫星标记;（5）分析临床和基因型数据， 使用各种统计方法的联系证据;以及（6）基于 连锁结果鉴定了候选基因组区域以供进一步研究。 将研究约1，500个主题。调查人员将 向科学界提供临床和生物学数据， 有助于绘制和克隆疾病基因。长期目标 将包括疾病基因的识别和表征 使用分子技术的范围;基因环境的阐明， 相互作用，并对具有连锁基因的病例进行表征， 并定义疾病的同质子集。这些长期目标 将在更新申请中考虑。 一系列独特的谱系的可用性，加上最近的 诊断程序、分子遗传学技术和 连锁分析方法，预示着解开遗传机制 是某些躁郁症的基础这反过来可能会导致 对病因学、疾病分类学、病理生理学和 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.