SEARCH FOR DNA MARKERS LINKED TO MANIC DEPRESSIVE ILLNESS IN THE OLD ORDER AMISH

我们正在对人类基因组进行系统的筛选， 确定老年人躁狂抑郁症的基因 命令阿米什人。 我们正在利用一个大型的多代旧秩序阿米什人 与许多受影响的个体的谱系。 通过使用这种多代 一个发病率高的家系，表现为相对 一致和可定义的表型，我们减少了分析中的不确定性， 否则可以引入为 遗传异质性的结果，遗传方式的变化， 表型模仿和/或非特异性。 候选基因已被研究。 高度信息化的标记，特别是分散在 基因组用于获得基因分型。 受影响个体的DNA 以确定三核苷酸扩增是否在 躁狂抑郁症的发病机制 由于缺乏任何 双相情感障碍的明确生物学标志物（躁狂抑郁 疾病），连锁分析是使用几个临床 等级制度 还进行了关联分析。 计算机 使用特定模型的模拟用于证明 分析。模拟和数据分析包括几个模型， 遗传和诊断层次，以及多基因病因。 随着标志物基因分型的积累，诊断数据得到更新， 我们收集了正常和患病家庭的细胞系 成员正在扩大。 纵向随访的可用性 对家庭成员的评价与躁狂抑郁症的高发 疾病的血统使旧秩序阿米什血统的一个宝贵的 在寻找双相情感障碍的遗传位点方面的资源 disorder.

We are performing a systematic screening of the human genome in order to identify a gene responsible for manic depressive disorder in the Old order Amish. We are utilizing a large multigenerational Old Order Amish pedigree with many affected individuals. By using this multigenerational pedigree with a high incidence of a disease manifested by a relatively consistent and definable phenotype, we reduce uncertainties in analysis that could otherwise be introduced as a consequence of genetic heterogeneity, variable mode of inheritance, phenocopies, and/or penetrance. Candidate genes have been studied. Highly informative markers particularly microsatellites scattered across the genome are used to obtain qenotypings. DNA of affected individuals is analyzed to ascertain whether trinucleotide expansions play a role in the pathogenesis of manic-depressive illness. Due to the lack of any definitive biological marker for bipolar illness (manic-depressive disorder), the linkage analyses are performed using several clinical hierarchies. Associative analyses are also carried out. Computer simulations using specific models are used to demonstrate the power of analyses. Simulation and data analysis includes several models of inheritance and diagnostic hierarchies, as well as polygenic etiologies. As marker genotypings are accumulated, the diagnostic data is updated, and our collection of cell lines from both normal and affected family member is being expanded. The availability of longitudinal follow-up evaluation for family members and the high frequency of manic depressive illness in the pedigree make the Old Order Amish pedigree a valuable resource in the search for the genetic loci involved in bipolar affective disorder.