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: 9047798
• 负责人: DAVID VALLE
• 金额: $ 309.99万
• 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/9047798
• 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（由适用提供）：识别负责孟德尔疾病的基因和变体的生物医学价值非常高。这些疾病的临床表现涉及几乎所有器官系统及其发育和物理参数。大约一半的公认的孟德尔疾病（在OMIM数据库中列举）仍无法在分子水平上解释，而其中的更多疾病仍有待认识。在过去的3.25年中，贝勒医学院和约翰·霍普金斯大学医学院人类遗传学计划结合并组成了贝勒 - 霍普金斯孟德尔基因组学中心（BHCMG），以找到孟德尔基因。在此过程中，我们通过结合了临床遗传学，基因组技术，遗传分析和理解遗传疾病的生物学基础方面的专业知识来利用提供的协同作用。我们已经见面并将通过利用我们的全球同事和前学员网络来应对研究主题的挑战。使用最先进的基因组方法和分析工具，我们已经对5,443个人的外显子组或基因组进行了测序，在前3。25年的资金中鉴定了169个新型疾病基因，并且有4,000多个样本准备从美国合作者和其他20个国家进行顺序。将来，我们将扩展此合作者网络，以确定更多样本。我们还开发了自动化过程，以联系OMIM中未知的Mendelian疾病的出版物作者，以招募其他特定的疾病例子。我们已经设计并通过IRB进行了在线同意过程，该过程绕过了国际和远程网站招聘中时间差和语言的瓶颈。为了简化和监视我们的进度，我们开发了PenoDB，这是一种基于网络的工具，用于收集，存储和分析疾病，表型特征和基因型信息。 PhanoDB还跟踪样本，并随着我们专家委员会的表型审查和ELSI问题的审议而更新。我们已经并且将继续建立在现有的高通量测序管道上，并与来自这两个机构的专家开发了集成的实验室和分析工作，以开发新的方法和软件以推进该领域。我们已经并且将通过出版，讲座，发布到公共网站和DBGAP来传播表型和分子信息。为了将临床医生和科学家感兴趣，并加速了对新型疾病基因鉴定的确认，我们开发了GeneMatcher，这是现在涉及世界各地基因的媒人交换计划的一部分。展望未来，为了教育医疗保健提供者和受训者，我们计划开发一门大规模的遗传学开放课程，并在增强招聘的同时对公众进行教育，我们将制定一系列在线教育视频。