GENETIC MARKERS IN AFFECTIVE DISORDERS

本继续申请的广泛目标是检测和 定位双相情感障碍和相关情感障碍的易感基因位点。 这一目标将由L. 39型扩展高密度双极 具有多态性DNA标记的谱系（这些是之前确定的 中型至大型的激酶，已建立的细胞系超过1000 计划的后续行动-见第3点-将扩大 样本总数接近2000人）;标记分型将集中在 系统扫描的基因组，包括候选基因，与特殊的 强调PCR技术和微卫星多态性; 2. 使用一系列表型和遗传分析进行连锁分析， 模型; 3.评估诊断更新和扩展的影响 联系结果的谱系（这将通过后续 研究已经确定的谱系，使用全面的临床 评级和操作诊断标准）。 在联系分析得出结果之前， 包括：疾病基因的鉴定和表征; 根据临床和生物学措施确定相关疾病形式; 阐明基因与环境的相互作用，并扩大谱系 复制连锁结果，评估遗传异质性， 如果合适，产生足够的减数分裂事件用于克隆 程序. 一系列独特的谱系的可用性，加上最近的 诊断程序、分子遗传技术的进展， 连锁分析，有望解开遗传机制， 是某些严重情感疾病的基础 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.