HETEROGENEITY OF BIPOLAR DISORDER

双相情感障碍是常见的和致残的表现，并且未知 病因学。它们是一种情绪障碍，可以通过 包括精神病在内的各种症状。人们对此知之甚少 但有令人信服的证据表明 遗传和环境因素在该病的病因中起一定作用 双相情感障碍。其机制尚不清楚。大多数调查人员 我相信双相情感障碍在病因上是不同的 相信他们可能有一些共同的易感基因 精神分裂症。 这项研究的长期目标是本地化和特征化 双相情感障碍的重要基因，并检验假设 双相情感障碍有一些基因决定的易感性 某种形式的精神分裂症。这将通过分子 遗传方法(即连锁分析和连锁不平衡 使用高度多态的微卫星标记的研究)。理解 导致这些疾病易感性的因素可能是 使受影响的个人及其亲属受益。身份识别 所涉及的基因可能为肿瘤的发展提供新的靶点。 改善这些疾病的药物。 此前已有研究表明，基因上的同质性更高 种群为鉴定黑热病提供了一定的优势 易感基因。在本申请中描述的努力中，我们 目的利用德系犹太人独特的遗传结构 使双相情感障碍的遗传解剖成为可能。这个 该提案的具体目标如下：1)招聘和评估 至少有两个受影响的200个德系犹太人家庭的样本 兄弟姐妹和至少一位父母愿意参与(兄弟姐妹对 2)招募和评估一个由300人组成的独立样本 被诊断为双相情感障碍的德系犹太人患者 以及其父母愿意参与(三人小组)。DNA将会是 分离和淋巴细胞将被分离，冷冻和储存 兄弟姐妹组和三人组中的个人；3)完成 以10厘米的分辨率进行全基因组扫描，使用HIGH Sib-Pair Panel中的多态基因座用于检测新的易感性 4)在Trio Panel中进行后续基因分型，以创建 在基因组扫描中确定的10个区域中有更密集的图谱 双相情感障碍易感基因的最多证据；5) 与这些家庭保持联系，以便有可能在 未来，以及6)将这一独特的临床资源提供给其他人 追求这一目标的调查人员。

Bipolar disorders are frequent and disabling expression and unknown etiology. They are disorders of mood that can be manifested with a variety of symptoms including psychosis. Little is known about the causes of bipolar disorder but there is convincing evidence that both genetic and environmental factors play some role in the etiology of bipolar disorder. The mechanism is not known. Most investigators believe that bipolar disorders are etiologically heterogeneous and some believe that they may share some susceptibility genes with schizophrenia. The long term objective of this research is to localize and characterize genes of importance to Bipolar Disorders and to test the hypothesis that bipolar disorders share some genetically determined susceptibility with some form of schizophrenia. This will be achieved through molecular genetic approaches (i.e., linkage analysis and linkage disequilibrium studies using highly polymorphic microsatellite markers). Understanding the factors that contribute to the susceptibility of these disorders may benefit affected individuals and their relatives. Identification of the genes involved may provide new targets for the development of medications to ameliorate these disorders. It has been previously shown that genetically more homogenous populations provide certain advantages to the identification of susceptibility genes. In the effort described in this application, we aim to use the unique genetic structure of the Ashkenazi Jewish population to enable a genetic dissection of bipolar disorders. The specific aims of the proposal are as follows: 1) to recruit and evaluate a sample of 200 Ashkenazi Jewish families with at least two affected siblings and at least one parent willing to participate (Sib Pair Panel); 2) to recruit and evaluate an independent sample of 300 Ashkenazi Jewish patients who are diagnosed as having bipolar disorder and whose parents are willing to participate (Trio Panel). DNA will be isolated and lymphocytes will be isolated, frozen and stored for individuals in both the Sib Pair and Trio Panels ; 3) to complete a genome wide scan at a resolution of 10 cM using well-mapped highly polymorphic loci in the Sib-Pair Panel to detect new susceptibility loci; 4) to perform follow-up genotyping in the Trio Panel to create a denser map in the 10 regions identified in the genome scan to have the most evidence for a susceptibility gene for bipolar disorders; 5) to maintain contact with these families so follow-up may be possible in the future, and 6) to make this unique clinical resource available to other investigators pursuing this goal.