Core C

Genetics Core将利用约翰斯夫妇收集的大量具有严格特征的临床样本 霍普金斯流行病学/遗传学项目在安·普尔弗博士的指导下确定了 在人类表型起源的项目1-3中确定的候选基因。此样本包括683个 德系犹太人(AJ)精神分裂症(SZ)或分裂情感性(SZA)先证者； 388名近交系(OB)SZ/SZA；85名OB双相I型(BP1)先证者；122名OB先证者 神经精神表型。每组一半到三分之二的人是亲子三人组，除了 OB、BP1和OB其他作为单胞胎的组。我们将执行和/或提供以下样品 对项目1-3中确定的候选基因进行测序、基因分型和基因分析。具体来说， 我们将：1)根据生物学证据和地图的力量对候选人进行优先排序 基于已发表的作品和我们自己小组的作品的信息；2)至少48个先驱 适当的无序，我们将对所有外显子和侧翼内含子序列加上近端启动子进行测序 区域(-500bp)和在序列保守基础上确定的任何候选调节区； 3)确定的序列变体(SV)将被优先排序，然后在适当的(取决于 诊断和人群组)使用TaqMan基因分型收集患者；4)分析频率和 我们病例中SV的分布和我们三人组中可能感兴趣的对照和基因分型 采样并执行TDT分析；以及5)与确定要执行的候选基因的小组合作 SV的功能分析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.