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.

识别负责孟德尔疾病的基因和变体的生物医学价值是 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（被列举 在OMIM数据库中）在分子水平上仍无法解释，其中许多疾病仍然存在 被认可，描述和解释。在过去的八年中，贝勒医学院和 约翰·霍普金斯大学医学院人类遗传学计划已结合并形成了 Mendelian Genomics（BHCMG）解决此问题的贝勒 - 霍普金斯中心（BHCMG）。这样，我们有 通过结合我们在临床遗传学，基因组中的专业知识来利用所提供的协同作用 技术，遗传分析和理解遗传疾病的生物学基础。我们已经见面了 将继续应对无法解释的研究患者寻找和招募的挑战 孟德尔（Mendelian）疾病，并利用我们的全球同事网络和前学员网络。使用状态 在ART基因组方法和分析工具中，我们已经测序了外来组或基因组 10,827个人，识别358个新型疾病基因，并有5,000个样本准备 来自美国和其他40个国家的合作者的顺序。这项工作导致了273个同伴 审查了BHCMG的论文。将来，我们将扩展此合作者网络，以确定更多 样品。为了协助来自世界各地的样本，我们设计了在线同意 我们的IRB批准的过程绕过了国际时间差异和语言的瓶颈 和远程招聘。简化和监视我们的进度，我们继续增强PnodB，一个 基于Web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，并随着我们的专家委员会的审议而更新 审查和ELSI问题。 PhenoDB是完全可搜索的，并结合了OMIM进行疾病分类和 基因以及许多其他资源来实现分析。我们已经并且将继续以我们的 现有的高通量测序管道，并开发了集成的实验室和分析工作 两家机构的专家都可以开发新的方法和软件来推进该领域。促进 数据共享，我们正在汇总在BCM和JH in的外显子组测序数据和表型数据 适用于联合分析的数据湖。我们已经并且将传播表型和分子 通过出版，讲座，发布到公共网站和DBGAP的信息。我们的种类 在线工具现在有> 7,000名调查人员提交的> 11,000个基因，并在> 150个出版物中引用，并且 媒人交流计划的一部分涉及世界各地的遗传学家。我们最近也有 在所有研究者都可以访问的PenoDB中添加了变体功能。

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