Human Participants and Sequencing

人类参与者和测序

• 批准号: 10024570
• 负责人: Jennifer M. Puck
• 金额: $ 26.43万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-08 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10024570
• 关键词: Address; Affect; Aliquot; Animal Model; Archives; B-Lymphocytes; Bioinformatics; Blood; Blood specimen; CD34 gene; CRISPR/Cas technology; Case Report Form; Cell Count; Cell Line; Cell Survival; Cell physiology; Cells; Clinical; Clinical Data; Code; Consent; Consent Forms; Cryopreservation; DNA; DNA Sequencing Facility; DNA sequencing; Data; Databases; Defect; Deposition; Diagnosis; Disease; Eligibility Determination; Enrollment; Ensure; Freezing; Functional disorder; Genes; Genetic; Genomic DNA; Genomics; Goals; Human; Human Herpesvirus 4; Immunology; Individual; Informed Consent; Inherited; Institutional Review Boards; Investigation; Lead; Liquid substance; Lymphocyte; Mediating; Neonatal Screening; Nitrogen; Ontology; Parents; Participant; Patients; Peripheral Blood Mononuclear Cell; Phenotype; Plasma; Protocols documentation; Provider; Publications; RNA; Rare Diseases; Records; Regulation; Research; Research Personnel; Role; Sampling; Sampling Studies; Secure; Severe Combined Immunodeficiency; Ships; Source; Spottings; Standardization; System; T-Lymphocyte; Testing; Training; United States National Institutes of Health; Untranslated RNA; Validation; Variant; Venous blood sampling; X-Linked Severe Combined Immunodeficiency; artemis; clinically relevant; congenital immunodeficiency; data de-identification; data exchange; deep sequencing; gene correction; genetic disorder diagnosis; genetic variant; genome editing; genome sequencing; human subject; novel strategies; personalized medicine; phenotypic data; population based; programs; rapid growth; screening; transcriptome; transcriptome sequencing; transforming virus; whole genome

CORE C, Human Participants and Sequencing: ABSTRACT The past decade has seen a rapid increase in diagnosis of genetic primary immunodeficiencies (PIDs) involving T lymphocyte dysfunction, in part due to the advent of population based newborn screening for severe combined immunodeficiency (SCID). This Program Project will combine new approaches that utilize deep sequencing, high-throughput cellular screening, genomics, gene editing, and functional testing in cellular systems and animal models to transform our understanding of human lymphocyte differentiation and function, and to create new, personalized treatments for affected individuals. The Projects and Cores of this Program will address the major challenges that have stood in the way of realizing this transformation by integrating clinical data from T-cell insufficient patients with basic investigations drawing on the expertise of leaders in immunology, bioinformatics, target validation, and genome editing. The Human Participants and Sequencing Core (Core C) serves the essential roles for the entire Program of (i) enrolling the human subjects, and (ii) conducting the deep sequencing. Subjects to be studied will be patients with T cell insufficiency or severe combined immunodeficiency (SCID) whose genetic diagnosis is unproven despite having had known genes responsible for these conditions investigated. Parents will be enrolled also. Core C will be the entry point and tracking hub for: informed consent, receiving samples, and collecting and recording phenotypic data (Aim 1); preparing samples for studies to be carried out by all the Projects and Cores (Aim 2); and obtaining special samples, including CD34+ primary cells from SCID patients for Projects 2 and 3 (Aim 3). Furthermore, Core C will obtain genomic DNA and cell-subset RNA sequencing for all Projects (Aim 2), sharing it, as permitted, with national databases to contribute to publicly available de-identified information on rare diseases (Aim 4).

核心C，人类参与者和测序：摘要 在过去的十年中，遗传原发免疫缺陷（PID）的诊断迅速增加 涉及T淋巴细胞功能障碍，部分原因是基于人口的新生儿筛查的出现 严重的联合免疫缺陷（SCID）。该程序项目将结合使用的新方法 深层测序，高通量细胞筛选，基因组学，基因编辑和功能测试 系统和动物模型，以改变我们对人类淋巴细胞分化和功能的理解， 并为受影响的个体创建新的个性化治疗方法。该计划的项目和核心 将解决通过整合来实现这一转变的主要挑战 来自T细胞的临床数据不足患者进行基本研究 免疫学，生物信息学，目标验证和基因组编辑。人类参与者和测序 核心（核心C）在（i）招募人类主题的整个程序和（ii）的整个程序中起着重要作用 进行深度测序。要研究的受试者将是T细胞功能不全或严重的患者 合并免疫缺陷（SCID），尽管有已知基因 负责调查的这些条件。父母也将入学。核心C将是入口点， 跟踪中心：知情同意，接收样本以及收集和记录表型数据（AIM 1）； 准备样本以由所有项目和核心进行研究（AIM 2）；并获得特价 样品，包括来自SCID患者的CD34+原代细胞，用于项目2和3（AIM 3）。此外，核心c 将获得所有项目（AIM 2）的基因组DNA和细胞 - 蛋白RNA测序 国家数据库有助于公开可用的有关罕见疾病的识别信息（AIM 4）。