MAPPING SCHIZOPHRENIA GENES IN DAGHESTANIAN ISOLATES

描述：(直接摘自摘要)：精神分裂症，折磨着 据估计占世界人口的0.5%到1%，是一种毁灭性的精神疾病 造成数不清的痛苦和损失的综合症。其中一个值得注意的方面是 疾病是尽管世界的文化和环境不同，但 疾病的流行和表现最引人注目的是相似。这个 精神分裂症的表现和病程在俄罗斯达吉斯坦没有什么不同， 但达吉斯坦的人口结构提供了独特的机会 探索这种毁灭性疾病的遗传病因学。特别是，一个 它的很大一部分人口是农村人，生活在与世隔绝的村庄里 友谊地久天长，同一个AUL的成员之间有大量的通婚。因此， 友谊地久天长本质上是大家庭，有些家庭有许多 受影响的个人，但其他人没有这种疾病。这种模式 这表明精神分裂症在达吉斯坦很大程度上是由基因引起的，这一点在达吉斯坦是正确的 世界各地的其他人口。我们的主要目标是确定 不同种族人群中精神分裂症易感性的基因 达吉斯坦的人口。 我们将从原始基因中确定12个“精神分裂症”大家族 分离物；每个分离物包含大量受影响的个体。大多数 12个基因孤立的家庭将来自达尔金族；一个很大的 该集团成立于约2000年前。到目前为止，9个大家庭已经 已部分查明，其中3个为达金家族；1个达金家族 有20例精神分裂症，另有30例，最大的有60例。三位一体 包含至少10个受影响个人的新家庭也将是 起源于达金。此外，100个较小的达金家庭至少有两个 受影响的个人将被确定。我们将使用来自 大型家庭进行基因组扫描和连锁分析以检测区域 基因组中含有影响精神分裂症易感性的基因。这些 被称为候选区域的区域将通过遗传和 对所有DNA样本进行统计分析，目的是区分 来自基因组扫描的真假信号和精确的位置 责任基因。最后，遗传和统计分析将尝试 通过评估几个密集的标记集合来定义易感性基因本身 候选区域，并通过对这些区域中的基因进行仔细评估 对精神分裂症有影响。

DESCRIPTION: (Directly from Abstract): Schizophrenia, which afflicts an estimated 0.5 to 1% of the world's population, is a devastating psychiatric syndrome that causes untold suffering and losses. A notable aspect of the disease is that despite differing cultures and environments of the world, the prevalence and presentation of disease are most noted for being similar. The presentation and course of schizophrenia is no different in Daghestan, Russia, but the population structure of Daghestan presents unique opportunities to explore the genetic etiology of this devastating illness. In particular, a large fraction of its population is rural, living in isolated villages called auls, with substantial intermarriage among members of the same aul. Thus the auls are essentially extended families, with some families have numerous affected individuals and yet the disease is absent in others. This pattern suggests a largely genetic origin of schizophrenia in Daghestan, as is true for other populations around the world. Our principal objective is to identify genes that underlie susceptibility to schizophrenia in the ethnically diverse population of Daghestan. We will ascertain 12 large "schizophrenia" families from primary genetic isolates; each containing a large number of affected individuals. Most of the 12 genetically isolated families will be from the Dargin ethnic group; a large group founded about 2000 years ago. To date, 9 large extended families have been partially ascertained, of which 3 are Dargin families; one Dargin family has 20 cases of schizophrenia, another has 30 and the largest has 60. The three new families, containing at least 10 affected individuals, also will be of Dargin origin. In addition, 100 smaller Dargin families having at least two affected individuals will be ascertained. We will use DNA samples from the large families to perform a genome scan and linkage analyses to detect regions of the genome harboring genes affecting liability to schizophrenia. These regions, called candidate regions, will be evaluated further by genetic and statistical analyses of all DNA samples, with the goal to distinguish between true and false signals from the genome scan and to refine the location of liability genes. Finally genetic and statistical analyses will attempt to define liability genes themselves by evaluating a dense set of markers in a few candidate regions and by close evaluation of genes in those regions plausibly having an impact on schizophrenia.