LINKAGE STUDIES OF SCHIZOPHRENIA

家庭、双胞胎和收养研究一致表明， 因素在精神分裂症中具有重要的病因学意义。月初以来 在这个世纪，有人提出，有单一的基因， 精神分裂症的“主要影响”分子生物学最新进展 和统计方法的联系分析，现在为我们提供， 第一次，严格评估这种说法的技术。 这是一项建议，对大量的 精神分裂症的多重家系， 在爱尔兰确定并取样（MH-41953）。本研究将使用 这些丰富的、高度多态的DNA标记， 几乎可以跨越整个人类基因组， 候选基因这项建议旨在利用独特的资源， 高密度爱尔兰精神分裂症谱系，包括：i）a 人口的种族构成相对单一， 减少遗传异质性的问题; ii）增强能力， 确定最佳诊断标准，并估计基因频率 利用所获得的数据进行连锁分析所需的遗传距离 根据一项大样本流行病学家庭研究， 即将完成的爱尔兰西部和iii）密切遗传 爱尔兰与冰岛和英格兰的关系， 其中已经确定的谱系显示出显著的 与5号染色体上的标记连锁。 整个基因组的遗传标记将被分型为高密度 精神分裂症家庭，首先集中在以前的地区， 研究表明可能与精神分裂症有关几 分离和联系分析的独特统计方法 将应用于数据，以充分利用其潜力。 任何强阳性结果将通过克隆额外的 来自基因组中的一个主要基因座的标记， 精神分裂症可能会说谎，为了更精确地绘制轨迹。

Family, twin and adoption studies have consistently shown that genetic factors are of major etiologic importance in schizophrenia. Since early in this century, it has been suggested that there are single genes of "major effect" for schizophrenia. Recent advances in molecular biology and in statistical approaches to linkage analysis now provide us, for the first time, with the techniques to rigorously evaluate this claim. This is a proposal to conduct linkage analyses on a large number of multiplex pedigrees for schizophrenia that are currently being ascertained and sampled in Ireland (MH-41953). This study will utilize the abundant, highly polymorphic DNA markers that have recently become available to span virtually the entire human genome as well as potential candidate genes. This proposal seeks to capitalize on the unique resource of high density Irish schizophrenic pedigrees that include: i) a relatively homogeneous ethnic composition of the population, which should reduce the problems of genetic heterogeneity; ii) enhanced ability to determine optimal diagnostic criteria, and estimates of gene frequency and penetrance necessary for linkage analyses by utilizing data obtained from a large sample epidemiologically based family study currently nearing completion in the West of Ireland and iii) the close genetic relationship between Ireland and both Iceland and England, the countries in which pedigrees have been ascertained that demonstrate significant linkage to markers on chromosome 5. Genetic markers throughout the genome will be typed for the high density schizophrenic families, first concentrating in areas that previous studies suggest might be of potential relevance to schizophrenia. Several distinct statistical methodologies of segregation and linkage analysis will be applied to the data in order to fully utilize their potential. Any strong positive findings will be pursued by cloning additional markers from that part of the genome where a major locus for schizophrenia might lie, in order to map the locus more precisely.