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筛选，以 确定与老年躁郁症相关的基因 叫阿米什人吧。我们正在利用一个庞大的，多代人的旧秩序阿米什人 有许多受影响的个体的谱系。通过使用这种多代人的 有疾病高发病率的家系，表现为 和可定义的表型，我们减少了分析中的不确定性，可以 否则是由于遗传异质性而引入的， 遗传、表型和/或外显性的不同模式。高度 信息性标记(RFLP、串联重复序列、二核苷酸重复序列等) 分散在基因组中的基因被用来获得基因分型。由于 在确定表型方面的不确定性，因为缺乏任何 双相情感障碍(躁郁症)的明确生物标志物 障碍)，使用几个临床数据进行连锁分析 层级结构。还进行了关联分析。电脑 使用特定模型的模拟被用来演示 分析。模拟和数据分析包括几个模型 遗传和诊断等级，以及多基因病因。 随着标记基因分型的积累，诊断数据被更新， 我们收集了来自正常家庭和患病家庭的细胞系 正在扩展成员。纵向随访的可用性 对家庭成员的评估与躁狂抑郁的高发 血统中的疾病使古老的阿米什血统变得有价值 寻找双相情感相关基因座的资源 无序。

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 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. Highly informative markers (RFLP, tandem repeats, dinucleotide repeats, etc.) scattered across the genome are used to obtain genotypings. Due to the uncertainties in ascertaining phenotype and because of 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.