IOWA MULTIPLEX FAMILY STUDY--MOLECULAR GENETICS

该项目的长期目标是识别基因突变， 易患精神分裂症来自家庭、双胞胎和收养研究的数据 这是一种遗传倾向，如果这些基因的分子基础 研究结果可以揭示它可能会导致我们的病理生理学的 疾病本身。该策略是使用多重谱系 精神分裂症的三种类型的遗传调查。 首先，精神分裂症的候选基因将在一个基因组中进行检查。 连锁设计，使用多态性DNA探针进行多重基因分型 血统第二，本项目的谱系将汇集在一个 利用人类基因图谱进行系统的协作， 找到致病基因我们将与犹他州集团合作，如果我们 被选为NIMH基因库的系谱收集中心，我们将 我们也在这方面进行合作。 我们提出的第三种方法是由确定的可能性决定的， 精神分裂症可能是太异质性找到疾病基因的任何一个 以上两种方法。这种可能性需要一种研究策略， 是基于个人的血统，其中一个是处理一个单一的 突变，而不是在合并的谱系集上。我们建议排序 在多重家系的先证者中仔细选择候选基因， 用于基因组DNA扩增聚合酶链反应和 用于获得序列数据的自动测序仪。血统将是 用于确定发现的任何序列变异是否与 这种疾病我们建议开始与多巴胺D2受体，因为 它在精神分裂症中的关键作用

The long range goal of this project is to identify genetic mutations that predispose the schizophrenia. Data from family, twin and adoption studies speak for a genetic predisposition, and if the molecular basis of these findings can be uncovered it may lead us to the pathophysiology of the disease process itself. The strategy is to use multiplex pedigrees of schizophrenia for three types of genetic investigation. First, candidate genes for schizophrenia will be examined in a genetic linkage design, using polymorphic DNA probes to genotype multiplex pedigrees. Second, pedigrees from this project will be pooled in a collaborative effort using the human gene map in a systematic effort to find disease genes. We will be collaborating with the Utah group, and if we are selected as a pedigree collection center for the NIMH gene bank we will collaborate on that effort as well. The third approach we propose is dictated by the definite possibility that schizophrenia may be too heterogeneous to find disease genes by either of the above two methods. This possibility calls for a research strategy that is based on individual pedigrees, where one is dealing with a single mutation, rather than on pooled pedigree sets. We propose sequencing careful selected candidate genes in probands from multiplex pedigrees using the polymerase chain reaction for genomic DNA amplification and an automated sequencer for obtaining the sequence data. The pedigrees will be used to determine whether any sequence variations found cosegregate with the disease. We propose to begin with the dopamine D2 receptor because of its key role in schizophrenia.