GENETIC MARKERS IN AFFECTIVE DISORDERS

此继续应用程序的主要目标是检测和 定位双相情感障碍和相关情感障碍的易感基因。 这一目标将通过L.键入39扩展的高密度双极来实现 具有多态DNA标记的家系(这些是先前确定的 建立了1000多个细胞系的中型到大型亲本 见多识广的成员；计划中的后续行动--见第三点--将扩大 总共向近2000个人提供样本)；标记打字将重点放在 对基因组的系统扫描，包括候选基因，具有特殊的 重视以聚合酶链式反应为基础的技术和微卫星多态性； 使用一系列表型和遗传进行连锁分析 模型；3.评估诊断更新和扩展的影响 关于连锁结果的谱系(这将由后续工作完成 应用综合临床方法对已鉴定的家系进行研究 评级和运行诊断标准)。 在链接分析的结果出来之前，长期目标将 包括：疾病基因的鉴定和特征(S)； 关于临床和生物措施的相关疾病形式的定义； 基因-环境互作的阐明和家系的扩展 复制连锁结果、评估遗传异质性的名册，以及 如果合适，为克隆产生足够的减数分裂事件 程序。 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，有望解开 某些形式的重大情感疾病是其基础。反过来，这可能会 ‘对病因学、病因学、病理生理学和 有可能，预防和治疗这些疾病。

The broad objective of this continuation application is to detect and localize susceptibility loci in bipolar and related affective disorders. This goal will be attained by l. typing 39 extended high-density bipolar pedigrees with polymorphic DNA markers (these are previously ascertained medium-to-large sized kindreds with established cell lines on over 1000 informative members; the planned follow-up- see point 3 - will enlarge the sample to nearly 2000 individuals altogether); marker typing will focus on systematic scan of the genome, including candidate genes, with special emphasis on PCR based technology and microsatellite polymorphisms; 2. performing linkage analysis using a range of phenotypic and genetic models; 3. assessing the impact of diagnostic update and extension of pedigrees on the linkage results (this will be accomplished by a follow-up study of the pedigrees already identified using comprehensive clinical ratings and operational diagnostic criteria). Pending the results of the linkage analyses, long-range goals will include: identification and characterization of the disease gene(s); definition of linked disease forms on clinical and biological measures; elucidation of gene-environment interaction; and expansion of the pedigree roster to replicate linkage results, assess genetic heterogeneity, and generate, if appropriate, sufficient meiotic events for the cloning procedures. The availability of a unique series of pedigrees, coupled with recent advances in diagnostic procedures, molecular genetic techniques, and linkage analysis, holds promise for unraveling the genetic mechanisms that underlie some forms of major affective illness. This, in turn, may have 'important implications for the etiology, nosology, pathophysiology and, possibly, prevention and treatment of these disorders.