Core C

遗传学核心将利用由约翰夫妇收集的大量且具有严格特征的临床样本

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.