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: 9923273
• 负责人: DAVID VALLE
• 金额: $ 231.89万
• 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 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9923273
• 关键词: Address; Biological; Biological Models; Bypass; Candidate Disease Gene; Clinical; Collection; Computer software; Consent; Country; Data; Databases; Detection; Development; Diagnosis; Disease; Etiology; Evaluation; Family; Funding; Future; Genes; Genetic; Genetic Diseases; Genetic Models; Genome; Genomics; Genotype; Health Personnel; High-Throughput Nucleotide Sequencing; Hospitals; Human Genetics; Individual; Information Dissemination; Institution; Institutional Review Boards; International; Joints; Knowledge; Laboratories; Language; Managed Care Programs; Measurement; Medical Genetics; Medicine; Mendelian disorder; Methods; Modeling; Molecular; Monitor; Mosaicism; Online Mendelian Inheritance In Man; Paper; Patient Recruitments; Patients; Peer Review; Persons; Phase; Phenotype; Physiological; Process; Publications; Reagent; Research; Research Personnel; Research Subjects; Resistance; Resources; Sampling; Sensitivity and Specificity; Site; Statistical Methods; System; Technology; Testing; Time; Travel; Universities; Update; Variant; Work; Zebrafish; analytical tool; base; body system; cohort; college; commune; computational pipelines; cost; data lake; data sharing; database of Genotypes and Phenotypes; design; disease classification; exome; exome sequencing; genetic analysis; genetic variant; genome analysis; genome sequencing; improved; lectures; massive open online courses; medical schools; meetings; member; mouse model; novel; phenotypic data; proband; programs; recruit; synergism; tool; transcriptome sequencing; virtual; web site; web-based tool; whole genome

The biomedical value of identifying the genes and variants responsible for Mendelian disorders is extraordinarily high. The clinical manifestations of these disorders involve developmental and physiological parameters of virtually all organ systems. About a third of recognized Mendelian disorders (as enumerated in the OMIM database) remain unexplained at the molecular level and many more of these disorders remain to be recognized, described and explained. Over the last eight years, the Baylor College of Medicine and Johns Hopkins University School of Medicine human genetics programs have combined and formed the Baylor-Hopkins Center for Mendelian Genomics (BHCMG) to address this problem. 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 finding and recruiting for our research patients with unexplained Mendelian disorders and 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 10,827 individuals, identifying 358 novel disease genes, and have another > 5,000 samples ready to sequence from collaborators in the USA and 40 other countries. This effort has resulted in 273 peer- reviewed papers from BHCMG. In the future, we will expand this network of collaborators to identify more samples. To assist in consenting samples from around the world, we have designed an online consenting process approved by our IRB that bypasses the bottlenecks of time difference and language in international and remote site recruiting. To streamline and monitor our progress we continue to enhance PhenoDB, a web-based tool for the collection, storage and analysis of phenotypic features and genotype information. PhenoDB also tracks samples, and is updated with the deliberations of our expert committees for Phenotype Review and ELSI issues. PhenoDB is fully searchable and incorporates OMIM for disease classification and genes, as well as many other resources to enable analysis. 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. To promote data sharing, we are aggregating exome sequencing data and phenotypic data produced at BCM and at JH in a data lake suitable for joint analysis. We have and will disseminate the phenotype and molecular information through publication, lectures, posting to communal websites and dbGaP. Our GeneMatcher online tool now has > 11,000 genes submitted by >7,000 investigators and cited in > 150 publications and is part of the MatchMaker Exchange initiative involving geneticists around the world. We have also recently added a VariantMatcher functionality to PhenoDB that is accessible to all investigators.

鉴定导致孟德尔疾病的基因和变异的生物医学价值是 非常高。这些疾病的临床表现涉及发育和生理 几乎所有器官系统的参数。大约三分之一的公认的孟德尔疾病（如所列举的 在 OMIM 数据库中）在分子水平上仍然无法解释，并且还有更多此类疾病 被认识、描述和解释。在过去的八年里，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合并并形成了 贝勒-霍普金斯孟德尔基因组学中心 (BHCMG) 致力于解决这一问题。这样做，我们有 利用结合我们在临床遗传学、基因组学方面的专业知识所提供的协同效应 技术、遗传分析和了解遗传病的生物学基础。我们已经相遇并 将继续迎接寻找和招募不明原因的研究患者的挑战 孟德尔疾病并利用我们的全球同事和前学员网络。使用状态 利用最先进的基因组方法和分析工具，我们已经对以下基因的外显子组或基因组进行了测序 10,827 个人，鉴定了 358 个新的疾病基因，并准备了另外超过 5,000 个样本 来自美国和其他 40 个国家的合作者的序列。这项努力已导致 273 名同行 审阅了 BHCMG 的论文。未来，我们将扩大这个合作者网络，以识别更多 样品。为了协助同意来自世界各地的样本，我们设计了一个在线同意书 经我们IRB批准的流程，绕过国际时差和语言的瓶颈 以及远程现场招聘。为了简化和监控我们的进展，我们继续增强 PhenoDB， 基于网络的工具，用于收集、存储和分析表型特征和基因型信息。 PhenoDB 还跟踪样本，并根据我们表型专家委员会的审议进行更新 审查和 ELSI 问题。 PhenoDB 完全可搜索，并结合 OMIM 进行疾病分类和 基因以及许多其他资源以进行分析。我们已经并将继续在我们的基础上继续发展 现有的高通量测序流程，并开发了集成的实验室和分析工作 与两个机构的专家一起开发新方法和软件来推进该领域的发展。推广 数据共享，我们正在汇总 BCM 和 JH 产生的外显子组测序数据和表型数据 适合联合分析的数据湖。我们已经并将传播表型和分子 通过出版物、讲座、发布到公共网站和 dbGaP 的方式获取信息。我们的基因匹配器 在线工具现在拥有超过 7,000 名研究人员提交的超过 11,000 个基因，并被超过 150 种出版物引用， 这是牵涉世界各地遗传学家的“媒人交流”计划的一部分。我们最近也有 向 PhenoDB 添加了 VariantMatcher 功能，所有研究人员都可以访问。

项目成果

Whole exome sequencing in a large pedigree with DCM identifies a novel mutation in RBM20.

对 DCM 大谱系的全外显子组测序发现了 RBM20 的新突变。

• DOI: 10.1080/00015385.2019.1674490
• 发表时间: 2020
• 期刊: Acta cardiologica
• 影响因子: 1.6
• 作者: Robyns,Tomas;Willems,Rik;VanCleemput,Johan;Jhangiani,Shalini;Muzny,Donna;Gibbs,Richard;Lupski,JamesR;Breckpot,Jeroen;Devriendt,Koenraad;Corveleyn,Anniek
• 通讯作者: Corveleyn,Anniek

First Case of CD40LG Deficiency in Ecuador, Diagnosed after Whole Exome Sequencing in a Patient with Severe Cutaneous Histoplasmosis.

厄瓜多尔首例 CD40LG 缺乏症，对一名严重皮肤组织胞浆菌病患者进行全外显子组测序后确诊。

• DOI: 10.3389/fped.2017.00017
• 发表时间: 2017
• 期刊: Frontiers in pediatrics
• 影响因子: 2.6
• 作者: Pedroza,LuisAlberto;Guerrero,Nina;Stray-Pedersen,Asbjørg;Tafur,Cristina;Macias,Roque;Muñoz,Greta;Akdemir,ZeynepCoban;Jhangiani,ShaliniN;Watkin,LeviB;Chinn,IvanK;Lupski,JamesR;Orange,JordanS
• 通讯作者: Orange,JordanS

Phenotypic heterogeneity associated with KIF21A: Two new cases and review of the literature.

与 KIF21A 相关的表型异质性：两个新病例和文献综述。

• DOI: 10.1002/ajmg.a.63455
• 发表时间: 2024
• 期刊: American journal of medical genetics. Part A
• 作者: Bhola,PriyaT;Mishra,Radha;Posey,JenniferE;Hamilton,LeslieE;Graham,GailE;Punetha,Jaya;Care4RareCanadaConsortium;Lupski,JamesR;Boycott,KymM;D'Amours,Damien;Kernohan,KristinD
• 通讯作者: Kernohan,KristinD

A Patient with Berardinelli-Seip Syndrome, Novel AGPAT2 Splicesite Mutation and Concomitant Development of Non-diabetic Polyneuropathy.

一名患有 Berardinelli-Seip 综合征、新型 AGPAT2 剪接位点突变并伴有非糖尿病性多发性神经病的患者。

• DOI: 10.4274/jcrpe.galenos.2018.2018.0227
• 发表时间: 2019
• 期刊: Journal of clinical research in pediatric endocrinology
• 影响因子: 1.9
• 作者: Oswiecimska,Joanna;Dawidziuk,Mateusz;Gambin,Tomasz;Ziora,Katarzyna;Marek,Marta;Rzonca,Sylwia;Guilbride,D.Lys;Jhangiani,ShaliniN.;Obuchowicz,Anna;Sikora,Alicja;Lupski,JamesR.;Wiszniewski,Wojciech;Gawlinski,Pawel
• 通讯作者: Gawlinski,Pawel

One Genetic Defect and Two Related Entities in Monozygotic Twins: Otosclerosis and Superior Semicircular Canal Near Dehiscence Syndrome.

• DOI: 10.7874/jao.2021.00381
• 发表时间: 2022-04
• 期刊: Journal of audiology & otology
• 影响因子: 1.1
• 作者: Ocal FCA;Kavus H;Satar B;Pehli van D
• 通讯作者: Pehli van D