ClinSeq

ClinSeq的具体目标包括： 1.试行开发强大的基础设施，以便在临床研究环境中生成和使用来自受试者的LSM数据。这将涉及NISC面向生产的DNA测序组与NIH临床研究中心的耦合。我们将建立生成、处理和解释LSM临床研究数据的技术专长。 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(如动脉粥样硬化和血脂水平)的相关性；(2)使用LSMS数据从预期队列中识别受试者亚组，然后邀请这些受试者返回国立卫生研究院临床研究中心进行进一步的表型鉴定和深入研究：以及(3)使用该队列进行基因组变异和表型相关性的复制研究。 美国国立卫生研究院临床研究中心将对1,000名受试者进行一系列心血管表型特征的评估，包括但不限于冠状动脉钙化、血脂和血压。参与者将被选为冠状动脉钙化从正常到疾病表型的范围内。参与者将接受临床评估、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。将对大约400个心血管表型候选基因的功能区域进行测序。重要的是，ClinSeq受试者将被同意进行全基因组测序，这样当技术进步时，样本可以用于测试研究受试者全基因组测序的可行性。ClinSeq的设计方式将为开展许多不同的临床项目提供长期潜力。我们建议从ClinSeq数据集中选择由他们的基因组属性识别的受试者的子集，探索他们的表型表现，作为理解基因型-表型关系的新途径。

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 will 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. Functional regions of about 400 candidate genes for the cardiovascular phenotype will be sequenced. Importantly, ClinSeq subjects will be consented for whole genome sequencing, so that when technology advances, the samples can be used to test the feasibility of whole genome sequencing of research subjects. 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.