GENETIC LINKAGE STUDIES IN AFFECTIVE DISORDERS

利用分子遗传技术，这项研究的主要目标是 建议深入研究X连锁双相情感障碍的致病基因 情感性疾病，并检测其他主要基因在 疾病的传播。这些目标将在1年前实现。 基因定位和相关的DNA技术；以及2.进行连锁 分离双相情感障碍合适家系的DNA标记研究 以及相关的情感障碍。这项研究还将旨在 在临床测量中确定关联病例与非关联病例的特征 尝试识别和定义疾病的同质子集 并比较不同的人口和种族群体是否可能 遗传差异。长期目标将包括克隆 缺陷基因.结构的测定.搜索 其生物制品；以及(基因-环境)评价 互动。 以色列是数据收集地。主要有六个原因 对于这个选择：1.X连锁的家系已经 已确认身份。2.大的多世代家系的可用性 有多个受影响的病例，随时可以进行研究。 3.酗酒和吸毒率低，情况令人困惑 精神病学诊断。4.有机会比较不同的人 人口和文化。5.之前的成功合作和 耐人寻味的发现需要扩展。6.相对较低的 人类研究的成本。以色列，可能是独一无二的，满足了所有这些 要求。 独特人口的可用性，加上最近 方法学上的进步，如分子基因技术， 系统地获取家庭数据的方法，结构化 面谈，准确的诊断标准，提高了可靠性； 以及一系列的遗传模型，为解开 情感性疾病背后的遗传机制。这个，在 反过来，可能会对病因学、病因学、 病理生理学以及可能的预防和治疗 精神错乱。

Using molecular genetic techniques, the chief objectives of this proposal are to home in on the disease gene in X-linked bipolar affective illness and to detect other major genes in the transmission of the disorder. These goals will be attained by 1. gene mapping and related DNA techniques; and 2. conducting linkage studies with DNA markers in suitable pedigrees segregating bipolar and related affective disorders. The study will also aim to characterize linked vs. unlinked cases on clinical measures in an attempt to identify and define homogeneous subsets of the disorder and to compare different populations and ethnic groups for possible genetic differences. Long-term goals will include cloning of the defective genes; determination of their structure; searching for their biological products; and assessment o( gene-environment interaction. Israel is the data collection site. There are six main reasons for this choice: 1. X-linked pedigrees have already been identified. 2. Availability of large multigenerational pedigrees with multiple affected cases that are readily accessible for study. 3. Low rates of alcoholism and drug use, conditions that confound the psychiatric diagnosis. 4. An opportunity to compare different populations and culture. 5. Previous successful collaboration and intriguing findings that require extension. 6. The relatively low cost of human research. Israel, probably uniquely, meets all these requirements. The availability of a unique population, coupled with recent methodological advances such as molecule genetic techniques, approaches to systematically obtaining family data, structured interviews, precise diagnostic criteria with improved reliability; and a range of genetic models, holds much promise for unraveling the genetic mechanisms that underlie affective illness. This, in turn, could have major implications for the etiology, nosology, pathophysiology and, possibly, prevention and treatment of these disorders.