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

在旧秩序阿米什人中寻找与躁狂抑郁症相关的 DNA 标记

• 批准号: 3845403
• 负责人: E I GINNS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3845403
• 关键词: Mennonite; behavioral genetics; bipolar depression; clone cells; computer simulation; family genetics; genetic disorder diagnosis; genetic mapping; genetic markers; genetic models; genotype; human genetic material tag; human subject; linkage mapping

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.

我们正在进行一个系统的 筛选人类基因组， 在老年人中鉴定出一种导致躁狂抑郁症的基因， 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人 与许多受影响的个体的谱系。 通过使用这种多代 一个具有高发病率的疾病表现为一致的 和可定义的表型，我们减少了分析中的不确定性， 否则将作为遗传异质性的结果引入， 可变的遗传模式、表型复制和/或突变。 高度 信息标记（RFLP、串联重复、二核苷酸重复等） 分散在基因组中的基因组序列用于获得基因分型。 由于 在确定表型的不确定性，因为缺乏任何 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 疾病的血统使古老的订单阿米什血统， 在寻找双相情感障碍的遗传位点方面的资源 disorder.