The ClinSeq Project: Piloting large-scale genome sequencing for research in genomic medicine
The ClinSeq Project: Piloting large-scale genome sequencing for research in genomic medicine
复制标题
DOI：
10.1101/gr.092841.109
复制
发表时间：
2009-09-01
期刊：
影响因子：
7
通讯作者：
Green, Eric D.
中科院分区：
文献类型：
--
作者：
Biesecker, Leslie G.;Mullikin, James C.;Green, Eric D.
ClinSeq 是一个试点项目，旨在研究使用全基因组测序作为临床研究工具。通过试点从个体人类受试者中获取大量 DNA 序列数据，我们正在促进开发用于进行基因组医学研究的假设生成方法，包括探索与疾病遗传结构相关的问题、实施基因组技术、知情同意、遗传信息披露以及存档、分析和显示序列数据。在 ClinSeq 的初始阶段，我们招募了大约 1000 名参与者；对每个人的评估包括获取详细的家族史和病史以及临床评估。参与者已获得广泛同意，可以进行许多性状的研究和全基因组测序。最初，我们正在对 300-400 个被认为与动脉粥样硬化相关的基因进行基于桑格的测序，并对所得数据进行分析，以找出与特定临床特征相关的罕见、高外显率变异。参与者还同意允许家庭成员联系以进行序列变异的额外研究，以探索它们与特定表型的潜在关联。在这里，我们介绍了设计 ClinSeq 时的一般考虑因素、基于生成初始 826 Mb 序列数据的初步结果、作为该项目阳性对照的几个基因的发现，以及我们对 ClinSeq 潜在影响的看法。 ClinSeq 的早期经验说明大规模医学测序如何成为基因组医学研究的实用、高效和关键组成部分。
ClinSeq is a pilot project to investigate the use of whole-genome sequencing as a tool for clinical research. By piloting the acquisition of large amounts of DNA sequence data from individual human subjects, we are fostering the development of hypothesis-generating approaches for performing research in genomic medicine, including the exploration of issues related to the genetic architecture of disease, implementation of genomic technology, informed consent, disclosure of genetic information, and archiving, analyzing, and displaying sequence data. In the initial phase of ClinSeq, we are enrolling roughly 1000 participants; the evaluation of each includes obtaining a detailed family and medical history, as well as a clinical evaluation. The participants are being consented broadly for research on many traits and for whole-genome sequencing. Initially, Sanger-based sequencing of 300-400 genes thought to be relevant to atherosclerosis is being performed, with the resulting data analyzed for rare, high-penetrance variants associated with specific clinical traits. The participants are also being consented to allow the contact of family members for additional studies of sequence variants to explore their potential association with specific phenotypes. Here, we present the general considerations in designing ClinSeq, preliminary results based on the generation of an initial 826 Mb of sequence data, the findings for several genes that serve as positive controls for the project, and our views about the potential implications of ClinSeq. The early experiences with ClinSeq illustrate how large-scale medical sequencing can be a practical, productive, and critical component of research in genomic medicine.