Core C

核心C

• 批准号: 8080402
• 负责人: DAVID VALLE
• 金额: $ 12.7万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8080402
• 关键词: Ashkenazim; Base Sequence; Biological; Biological Assay; Candidate Disease Gene; Child; Clinical; Collection; Diagnosis; Disease; Epidemiology; Exons; Frequencies; Genes; Genetic; Genetic Programming; Genomics; Genotype; Human; Maps; Nucleic Acid Regulatory Sequences; Parents; Patients; Phenotype; Population Group; Promoter Regions; Publishing; Role; Sampling; Schizophrenia; Variant; Work; base; case control; clinical phenotype; follower of religion Jewish; genetic analysis; interest; neuropsychiatry; proband

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.

遗传学核心将利用约翰群岛收集的大型且严格的临床样本 霍普金斯流行病学/遗传学计划在Ann Pulver博士的指导下确定 在人类表型的起源中，在项目1-3中鉴定出的候选基因。该样本包括683 Ashkenazi犹太人（AJ）精神分裂症（SZ）或精神分裂症（SZA）概率； 1090 AJ筛选控件； 388近亲（OB）SZ/SZA; 85 OB双极I（BP1）概率；和122个与相关的OB概率 神经精神病表型。每组的一半到三分之二之间是作为亲子三个的，除了 OB BP1和OB的其他类别是单身人士。我们将执行和/或提供样品 在项目1-3中鉴定的候选基因的测序，基因分型和遗传分析。具体来说， 我们将：1）优先考虑候选人在生物学证据的强度上以及映射 基于我们自己小组的已发表工作和工作的信息； 2）至少有48个概率 适当的疾病，我们将对所有外显子和内含子序列以及近端启动子进行测序 区域（-500 bp）和根据序列保守性确定的任何候选监管区域； 3）确定的序列变体（SV）将优先级，然后在适当的情况下进行基因分型（取决于 诊断和人口组）使用Taqman基因分型收集患者； 4）分析频率和 在我们的案例中分配SV，控制和基因型，这些人似乎在我们的三重奏中感兴趣 样品并执行TDT分析； 5）与小组一起识别候选基因以执行 SV的功能测定与临床表型显着相关。