Baylor Johns Hopkins Center for Mendelian Genetics

贝勒约翰霍普金斯孟德尔遗传学中心

• 批准号: 9269870
• 负责人: DAVID VALLE
• 金额: $ 22.06万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-12-05 至 2019-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9269870
• 关键词: Biological; Biological Models; Bypass; Candidate Disease Gene; Clinical; Collection; Communities; Computer software; Consent; Country; Data; Databases; Detection; Development; Disease; Etiology; Evaluation; Family; Funding; Future; Genes; Genetic; Genetic Models; Genetic Programming; Genome; Genomics; Genotype; Health Personnel; Hereditary Disease; High-Throughput Nucleotide Sequencing; Hospitals; Human; Human Genetics; Individual; Information Dissemination; Institution; Institutional Review Boards; International; Knowledge; Laboratories; Language; Managed Care Programs; Measurement; Medical Genetics; Medicine; Mendelian disorder; Methods; Modeling; Molecular; Monitor; Mosaicism; Online Mendelian Inheritance In Man; Online Systems; Paper; Patients; Persons; Phase; Phenotype; Physiological; Process; Publications; Publishing; Reading; Reagent; Recruitment Activity; Research Personnel; Research Subjects; Resistance; Sampling; Scientist; Sensitivity and Specificity; Sequence Analysis; Site; Statistical Methods; System; Technology; Testing; Time; Travel; Universities; Update; Variant; Work; Zebrafish; base; body system; cohort; college; cost; database of Genotypes and Phenotypes; design; exome; exome sequencing; genetic analysis; genetic variant; genome sequencing; improved; innovation; interest; lectures; massive open online courses; medical schools; meetings; member; molecular diagnostics; molecular phenotype; mouse model; new technology; novel; proband; programs; public health relevance; success; tool; transcriptome sequencing; web site; whole genome

 DESCRIPTION (provided by applicant): The biomedical value of identifying the genes and variants responsible for Mendelian disorders is extraordinarily high. The clinical manifestations of these disorders involve virtually all organ systems and their developmental and physiological parameters. About half of recognized Mendelian disorders (as enumerated in the OMIM database) remain unexplained at the molecular level and many more of these remain to be recognized. Over the last 3.25 years, the Baylor College of Medicine and the Johns Hopkins University School of Medicine human genetics programs have combined and formed the Baylor-Hopkins Center for Mendelian Genomics (BHCMG) to find Mendelian genes. In doing so, we have taken advantage of the synergies afforded by combining our expertise in clinical genetics, genomic technologies, genetic analysis and understanding the biological basis of genetic disease. We have met and will continue to meet the challenge of research subjects by utilizing our worldwide network of colleagues and former trainees. Using state of the art genomic methods and analytic tools, we have already sequenced the exome or the genome of 5,443 individuals, identifying 169 novel disease genes in the first 3.25 years of funding, and have more than 4,000 samples ready to sequence from collaborators in the USA and >20 other countries. In the future, we will expand this network of collaborators to identify even more samples. We have also developed automated processes to contact the authors of publications from unexplained Mendelian disorders in OMIM to recruit additional specific disease examples. We have designed and passed through the IRB an online consenting process that bypasses the bottlenecks of time difference and language in international and remote site recruiting. To streamline and monitor our progress we have developed PhenoDB, a web-based tool for the collection, storage and analysis of disease, phenotypic feature and genotype information. PhenoDB also tracks samples, and is updated with the deliberations of our expert committees for Phenotype Review and ELSI issues. We have and will continue to build on our existing high throughput sequencing pipelines and have developed integrated laboratory and analysis efforts with experts from both institutions to develop new methods and software to advance the field. We have and will disseminate the phenotype and molecular information through publication, lectures, posting to communal websites and dbGaP. To connect clinicians and scientists with interest in the same gene and accelerate confirmation of novel disease gene identification, we developed GeneMatcher, now part of the MatchMaker Exchange initiative involving geneticists around the world. Going forward, to educate health care providers and trainees, we plan to develop a Massive Open Online Course in genetics, and to educate the public while enhancing recruitment, we will develop a set of online educational videos.

 描述(由申请人提供)：识别导致孟德尔疾病的基因和变异的生物医学价值非常高。这些疾病的临床表现几乎涉及所有器官系统及其发育和生理参数。大约一半已确认的孟德尔病症(如OMIM数据库中所列举的)仍未在分子水平上得到解释，还有更多的病症仍有待确认。在过去的3.25年里，贝勒医学院和约翰霍普金斯大学医学院的人类遗传学项目联合起来，成立了贝勒-霍普金斯孟德尔基因组学中心(BHCMG)，以寻找孟德尔基因。在这样做的过程中，我们利用了通过结合我们在临床遗传学、基因组技术、基因分析和了解遗传病的生物学基础方面的专业知识而产生的协同效应。我们已经并将继续利用我们的全球同事和前受训人员网络，迎接研究课题的挑战。使用最先进的基因组方法和分析工具，我们已经对5443个人的外显子组或基因组进行了测序，在最初3.25年的资助中识别了169个新的疾病基因，并从美国和其他20个国家的合作者那里准备了4000多个样本进行测序。在未来，我们将扩大这个合作者网络，以确定更多的样本。我们还开发了自动化程序来联系OMIM中未解释的孟德尔疾病出版物的作者，以招募更多特定的疾病例子。我们设计并通过了IRB，这是一个在线同意程序，绕过了国际和远程现场招聘中的时差和语言瓶颈。为了简化和监测我们的进展，我们开发了PhenoDB，这是一个基于网络的工具，用于收集、存储和分析疾病、表型特征和基因信息。PhenoDB还跟踪样本，并根据我们的表型审查和ELSI问题专家委员会的审议情况进行更新。我们已经并将继续在我们现有的高通量测序管道的基础上进行建设，并与两家机构的专家一起开展综合实验室和分析工作，以开发新的方法和软件来推动该领域的发展。我们已经并将通过出版、讲座、在公共网站和DBGaP上张贴来传播表型和分子信息。为了联系对同一基因感兴趣的临床医生和科学家，并加速确认新的疾病基因鉴定，我们开发了GeneMatcher，现在是世界各地遗传学家参与的媒人交流倡议的一部分。展望未来，为了教育卫生保健提供者和受训人员，我们计划开发一个大规模的遗传学在线开放课程，并在加强招聘的同时教育公众，我们将开发一套在线教育视频。