Core C

遗传学核心将利用约翰收集的大量和严格表征的临床样本 霍普金斯流行病学/遗传学项目在Ann Pulver博士的指导下， 在项目1-3中鉴定的人类表型发生中的候选基因。该样本包括683个 德系犹太人（AJ）精神分裂症（SZ）或情感性精神分裂症（SZA）先证者; 1090名AJ筛选对照; 388例远交（OB）SZ/SZA; 85例OB双极I型（BP 1）先证者; 122例OB先证者有相关 神经精神表型每组的一半到三分之二是父母和孩子三人组，除了 OB BP 1和OB其他组作为单例。我们将执行和/或提供样品， 对项目1-3中确定的候选基因进行测序、基因分型和遗传分析。具体地说， 我们将：1）根据生物学证据和绘图的强度对候选人进行优先排序 基于已发表的工作和我们自己小组的工作的信息; 2）在至少48个先证者中， 适当的疾病，我们将测序所有外显子和侧翼内含子序列加上近端启动子 区域（~ 500 bp）和基于序列保守性鉴定的任何候选调控区域; 3)将对识别的序列变体（SV）进行优先排序，然后以适当的方式进行基因分型（取决于 诊断和人群组）患者收集; 4）分析频率和 SV在我们病例和对照组中的分布，以及对我们三组中感兴趣的SV进行基因分型 取样并进行TDT分析;和5）与鉴定候选基因的小组一起工作，以进行 SV的功能测定显示与临床表型显著相关。

The Genetics Core will utilize the large and rigorously characterized clinical sample collected by the Johns Hopkins Epidemiology/Genetics program under the direction of Dr. Ann Pulver to determine the role of candidate genes identified in Projects 1-3 in the genesis of human phenotypes. This sample includes 683 Ashkenazi Jewish (AJ) schizophrenia (SZ) or schizoaffective (SZA) probands; 1090 AJ screened controls; 388 outbred (OB) SZ/SZA; 85 OB bipolar I (BP1) probands; and 122 OB probands with related neuropsychiatric phenotypes. Between half to two thirds of each group is as parent-child trios except for the OB BP1 and OB other groups which are as singletons. We will perform and/or provide the samples for sequencing, genotyping and genetic analysis of the candidate genes identified in Projects 1-3. Specifically, we will: 1) Prioritize the candidates on the strength of the biological evidence together with mapping information based on published work and work from our own group; 2) In at least 48 probands for the appropriate disorder, we will sequence all exons and flanking intronic sequence plus the proximal promoter region (-500 bp) and any candidate regulatory regions identified on the basis of sequence conservation; 3) Identified sequence variants (SV) will be prioritized and then genotyped in the appropriate (depending on diagnosis and population group) patient collection using TaqMan genotyping; 4) Analyze the frequency and distribution of the SV in our cases and controls and genotype those that appear to be of interest in our trio sample and perform TDT analysis; and 5) Work with the group identifying the candidate gene to perform functional assays of SV shown to be significantly associated with the clinical phenotype.