ClinSeq

临床测序

• 批准号: 8565558
• 负责人: Leslie Biesecker
• 金额: $ 125.61万
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8565558
• 关键词: Address; Atherosclerosis; Biomedical Research; Blood Pressure; Blood specimen; Cardiac; Cardiomyopathies; Cardiovascular system; Categories; Clinical; Clinical Research; Consent; Coupling; DNA; DNA Sequence; Data; Data Set; Development; Disease; Family; Generations; Genetic Counseling; Genomics; Genotype; Health behavior; Individual; Lipids; Malignant Neoplasms; Malignant hyperpyrexia due to anesthesia; Medical; Medical Genetics; Participant; Peripheral; Persons; Phenotype; Predisposition; Production; Recording of previous events; Reporting; Research; Research Infrastructure; Sampling; Technical Expertise; Testing; United States National Institutes of Health; Variant; cohort; coronary artery calcification; design; disease phenotype; exome; falls; nervous system disorder; peripheral blood; prospective; research clinical testing; sample collection; trait

The specific aims of ClinSeq include: 1. Pilot the development of a robust infrastructure for the generation and use of LSMS data from subjects in a clinical research setting. This will involve the coupling of the NISC production-oriented DNA sequencing group with the NIH Clinical Research Center. We will establish technical expertise for generating, handling, and interpreting LSMS clinical research data. 2. Use LSMS data to address biomedical research questions. For example: (l) testing associations of genomic variants with quantitative traits identified in subjects (such as atherosclerosis and lipid levels); (2) using LSMS data to identify subsets of subjects from the prospective cohort, who can then be invited to return to the NIH Clinical Research Center for additional phenotyping and in-depth study: and (3) using this cohort for replication studies of associations of genomic variants and phenotypes. A cohort of 1,000 individuals will be evaluated at the NIH Clinical Research Center for a set of cardiovascular phenotypic features, including, but not limited to, coronary artery calcification, lipid profiles, and blood pressure. Participants will be selected to fall within a spectrum of coronary artery calcification from normal to disease phenotype. Participants undergo a clinical evaluation, targeted clinical tests, and blood sample collection for genomic analysis and they will provide baseline information about pertinent health behavior and a family history. Exome sequencing of peripheral blood DNA will be performed on all samples and has been completed in >800 subjects to date. Importantly, ClinSeq subjects will be consented for return of results (both research and clinical results) and for re-contact for iterative phenotyping. ClinSeq was designed in a way that will provide the long-term potential for pursuing many different clinical projects. We propose to select subsets of subjects from the ClinSeq dataset, identified by their genomic attributes, explore their phenotypic manifestations, as a new path to understanding genotype-phenotype relationships. In the most recent reporting period we have successfully interpreted exomes of 600 participants for serious, disease-causing variants in a number of disease categories including cancer susceptibility, cardiomyopathy, cardiac dysrhythmias, malignant hyperthermia, and peripheral neurologic disorders. We are currently annotating subjects for an addition set of rare dominant disorders and recessive carrier status.

ClinSeq 的具体目标包括： 1. 试点开发强大的基础设施，用于在临床研究环境中生成和使用受试者的 LSMS 数据。这将涉及 NISC 以生产为导向的 DNA 测序小组与 NIH 临床研究中心的结合。 我们将建立生成、处理和解释 LSMS 临床研究数据的技术专业知识。 2. 使用 LSMS 数据解决生物医学研究问题。例如：（l）测试基因组变异与受试者中确定的数量性状（例如动脉粥样硬化和血脂水平）的关联； (2) 使用 LSMS 数据从前瞻性队列中识别受试者子集，然后可以邀请他们返回 NIH 临床研究中心进行额外的表型分析和深入研究：以及 (3) 使用该队列进行关联的复制研究基因组变异和表型。 NIH 临床研究中心将评估 1,000 名个体的一组心血管表型特征，包括但不限于冠状动脉钙化、血脂谱和血压。参与者将被选择属于从正常表型到疾病表型的冠状动脉钙化范围。参与者接受临床评估、有针对性的临床测试和血液样本采集以进行基因组分析，他们将提供有关相关健康行为和家族史的基线信息。将对所有样本进行外周血 DNA 外显子组测序，迄今为止已在超过 800 名受试者中完成。重要的是，ClinSeq 受试者将同意返回结果（研究和临床结果）并同意重新接触以进行迭代表型分析。 ClinSeq 的设计方式将为追求许多不同的临床项目提供长期潜力。我们建议从 ClinSeq 数据集中选择受试者子集，通过其基因组属性进行识别，探索其表型表现，作为理解基因型-表型关系的新途径。 在最近的报告期内，我们已成功解读了 600 名参与者的外显子组，以找出许多疾病类别中的严重致病变异，包括癌症易感性、心肌病、心律失常、恶性高热和周围神经系统疾病。我们目前正在注释一组额外的罕见显性疾病和隐性携带者状态的受试者。