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 叫阿米什人 我们正在利用一个庞大的，多代的旧秩序 阿米什血统与许多受影响的个人。 通过使用该 一个多代同堂的家系， 通过相对一致和可定义的表型，我们减少了 分析中的不确定性，否则可能会被引入作为一个 遗传异质性的结果，可变的遗传模式， 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 也进行了分析，以确定是否三核苷酸扩增发挥作用， 在躁狂抑郁症发病机制中的作用。 由于缺乏 双相情感障碍（躁狂抑郁症 疾病），连锁分析是使用几个临床 等级制度 参数（LOD评分，最大似然）和 非参数（受累同胞对、受累家系成员等） 进行了分析。 使用特定模型的计算机模拟是 用来证明分析的力量。 模拟和数据分析 包括继承和诊断层次结构的几种模型， 以及多基因病因学。 随着标记基因分型的积累， 更新诊断数据，我们收集的细胞系来自 正常和受影响的家庭成员正在扩大 ded。 家庭纵向随访评价的可行性 成员和高频率的躁狂抑郁症， 血统使旧秩序阿米什血统的宝贵资源， 寻找与双相情感障碍有关的基因位点。

We are performing a systematic screening of the human genome in order to identify genes 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 genotypings. DNA of affected individuals is also 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. Parametric (LOD scored, maximum likelihood) and nonparametric (affected sib pair, affected pedigree member, etc.) analyses are 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 expan ded. 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.