Green Robert C, Goddard Katrina A B, Jarvik Gail P, Amendola Laura M, Appelbaum Paul S, Berg Jonathan S, Bernhardt Barbara A, Biesecker Leslie G, Biswas Sawona, Blout Carrie L, Bowling Kevin M, Brothers Kyle B, Burke Wylie, Caga-Anan Charlisse F, Chinnaiyan Arul M, Chung Wendy K, Clayton Ellen W, Cooper Gregory M, East Kelly, Evans James P, Fullerton Stephanie M, Garraway Levi A, Garrett Jeremy R, Gray Stacy W, Henderson Gail E, Hindorff Lucia A, Holm Ingrid A, Lewis Michelle Huckaby, Hutter Carolyn M, Janne Pasi A, Joffe Steven, Kaufman David, Knoppers Bartha M, Koenig Barbara A, Krantz Ian D, Manolio Teri A, McCullough Laurence, McEwen Jean, McGuire Amy, Muzny Donna, Myers Richard M, Nickerson Deborah A, Ou Jeffrey, Parsons Donald W, Petersen Gloria M, Plon Sharon E, Rehm Heidi L, Roberts J Scott, Robinson Dan, Salama Joseph S, Scollon Sarah, Sharp Richard R, Shirts Brian, Spinner Nancy B, Tabor Holly K, Tarczy-Hornoch Peter, Veenstra David L, Wagle Nikhil, Weck Karen, Wilfond Benjamin S, Wilhelmsen Kirk, Wolf Susan M, Wynn Julia, Yu Joon-Ho
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Partners Personalized Medicine, Boston, MA 02139, USA.
Center for Health Research, Kaiser Permanente Northwest, Portland, OR 97227, USA.
Am J Hum Genet. 2016 Jun 2;98(6):1051-1066. doi: 10.1016/j.ajhg.2016.04.011. Epub 2016 May 12.
Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine.
尽管技术进步迅速，且在某些类型的诊断和治疗中已证明具有有效性，但关于临床基因组和外显子组测序（CGES）及其在医学实践中的作用，仍有许多有待了解。临床测序探索性研究（CSER）联盟包括18个校外研究项目、1个国家人类基因组研究所（NHGRI）的校内项目，以及一个由NHGRI和国家癌症研究所资助的协调中心。该联盟正在通过多学科方法探索测序的分析和临床有效性及实用性，以及伦理、法律和社会影响；到目前为止，通过利用种系和癌症测序，已招募了5577名有症状和健康的儿童及成人参与者。CSER联盟正在分析数据，并创建与参与者偏好和同意、变异分类、一级和二级发现的披露与管理、健康结果以及与电子健康记录整合相关的公开可用程序和工具。未来的研究方向将完善CGES在种系和体细胞检测中的临床实用性测量方法，评估CGES在健康个体筛查中的应用，通过广泛的表型分析探索致病变异的外显率，减少基因和变异公共数据库中的不一致性，研究基因组学服务提供中的社会和种族差异，探索监管问题，并估计测序的价值和下游成本。CSER联盟通过采用多种方法，建立了一个研究站点共享社区，以追求基于证据的基因组医学最佳实践的发展。
