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: 8845225
• 负责人: DAVID VALLE
• 金额: $ 387.09万
• 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 2016-01-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8845225
• 关键词: Affect; Biological; Clinical; Communities; Computer Analysis; Computer software; Consanguinity; Copy Number Polymorphism; Country; DNA; Data; Data Analyses; Data Linkages; Databases; Detection; Diagnosis; Disease; E-learning; Educational workshop; Failure; Family; Gene Mutation; Genes; Genetic; Genetic Programming; Genome; Genomics; Genotype; Hand; Hereditary Disease; Heterozygote; Human; Human Genetics; Individual; Institution; Laboratories; Leukocytes; Medical; Medical Genetics; Medicine; Mendelian disorder; Methods; Molecular; Molecular Analysis; Monitor; Mutation; Nature; Online Mendelian Inheritance In Man; Online Systems; Patients; Phenotype; Production; Public Domains; Rare Diseases; Recruitment Activity; Relative (related person); Research Personnel; Resources; Review Committee; Sampling; Sequence Analysis; Software Tools; Technology; Training; Universities; Variant; adjudication; base; college; disease classification; exome; exome sequencing; family structure; genetic analysis; genetic variant; genome sequencing; genome-wide; improved; medical schools; meetings; proband; programs; protein structure; segregation; trait; web based interface; web site

Although, the biological and medical value of identifying the genes and variants responsible for Mendelian disorders is extraordinarily high, the vast majority of these remain unexplained at the molecular level. To this end, we will create a partnership between two of the oldest and most accomplished human genetics programs in the country, those at Baylor College of Medicine (BCM) and Johns Hopkins University School of Medicine (JHUSOM), to form the Baylor-Hopkins Center for Mendelian Genomics (BHCMG). In doing so, we will take advantage of our complete access to OMIM and of the synergies afforded by combining our expertise in clinical genetics, genomic technologies, genetic analysis and understanding the biological basis of genetic disease. We will meet the challenge of finding and recruiting samples representing these rare disorders by creating and utilizing a worldwide network of colleagues and former trainees to identify and recruit thousands of patients and families with unexplained Mendelian phenotypes or with undiagnosed disease that segregates in their families as Mendelian traits. We already have >2,000 DNA samples in hand at our two institutions and have identified > 12,000 DNA samples in our network of 17 collaborators around the world. Moreover, we have developed strategies to utilize OMIM (>10, 000 unique hits/day) to flag unexplained phenotypes and recruit samples. We will further organize our efforts by building a sample and disease-tracking database that is integrated with and accessible through OMIM as well as through a BHCMG web site and have assembled a committee of experts to assist with the inevitable ELSI issues. We will build on our existing high throughput genotyping and sequencing pipelines to develop an integrated laboratory effort and we will use a committee of experts from both institutions plus outside experts to analyze the data and develop new software tools to advance the field. Finally, to disseminate the phenotypic and molecular information we will follow an aggressive plan of data dissemination using OMIM and other web-based resources as well as organizing an annual Mendelian genetics meeting open to all.

虽然，识别孟德尔疾病的基因和变异的生物学和医学价值是非常高的，但其中绝大多数在分子水平上仍然无法解释。为此，我们将在贝勒医学院（BCM）和约翰霍普金斯大学医学院（JHUSOM）这两个美国历史最悠久、最具成就的人类遗传学项目之间建立合作关系，组建贝勒-霍普金斯孟德尔基因组学中心（BHCMG）。在这样做的过程中，我们将充分利用我们对OMIM的全面访问，以及通过结合我们在临床遗传学、基因组技术、遗传分析和了解遗传病的生物学基础方面的专业知识所提供的协同效应。我们将迎接寻找和招募代表这些罕见疾病的样本的挑战，通过创建和利用一个由同事和前学员组成的全球网络来识别和招募数千名患有无法解释的孟德尔表型或未确诊疾病的患者和家庭，这些疾病在他们的家庭中作为孟德尔特征分离。在我们的两个机构中，我们已经有了2000个DNA样本，并在我们全球17个合作者的网络中鉴定了12000个DNA样本。此外，我们已经制定了利用OMIM（每天10万次独特点击）标记无法解释的表型和招募样本的策略。我们将进一步组织我们的工作，建立一个样本和疾病跟踪数据库，该数据库与OMIM和BHCMG网站相结合并可通过该数据库访问，并已组建了一个专家委员会，协助处理不可避免的ELSI问题。我们将在现有的高通量基因分型和测序管道的基础上开发一个综合实验室，我们将使用来自两个机构的专家委员会和外部专家来分析数据并开发新的软件工具来推进该领域。最后，为了传播表型和分子信息，我们将遵循一项积极的计划，利用OMIM和其他基于网络的资源进行数据传播，并组织一年一度的孟德尔遗传学会议向所有人开放。

项目成果

GeneMatcher aids in the identification of a new malformation syndrome with intellectual disability, unique facial dysmorphisms, and skeletal and connective tissue abnormalities caused by de novo variants in HNRNPK.

GeneMatcher有助于鉴定出具有智力障碍，独特的面部畸形以及HNRNPK中从头变体引起的骨骼和结缔组织异常的新畸形综合征。

• DOI: 10.1002/humu.22837
• 发表时间: 2015-10
• 期刊: Human mutation
• 影响因子: 3.9
• 作者: Au PYB;You J;Caluseriu O;Schwartzentruber J;Majewski J;Bernier FP;Ferguson M;Care for Rare Canada Consortium;Valle D;Parboosingh JS;Sobreira N;Innes AM;Kline AD
• 通讯作者: Kline AD

PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment.

• DOI: 10.1093/brain/awx014
• 发表时间: 2017-04-01
• 期刊: Brain : a journal of neurology
• 作者: Zollo M;Ahmed M;Ferrucci V;Salpietro V;Asadzadeh F;Carotenuto M;Maroofian R;Al-Amri A;Singh R;Scognamiglio I;Mojarrad M;Musella L;Duilio A;Di Somma A;Karaca E;Rajab A;Al-Khayat A;Mohan Mohapatra T;Eslahi A;Ashrafzadeh F;Rawlins LE;Prasad R;Gupta R;Kumari P;Srivastava M;Cozzolino F;Kumar Rai S;Monti M;Harlalka GV;Simpson MA;Rich P;Al-Salmi F;Patton MA;Chioza BA;Efthymiou S;Granata F;Di Rosa G;Wiethoff S;Borgione E;Scuderi C;Mankad K;Hanna MG;Pucci P;Houlden H;Lupski JR;Crosby AH;Baple EL
• 通讯作者: Baple EL

Family Based Whole Exome Sequencing Reveals the Multifaceted Role of Notch Signaling in Congenital Heart Disease.

• DOI: 10.1371/journal.pgen.1006335
• 发表时间: 2016-10
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Preuss C;Capredon M;Wünnemann F;Chetaille P;Prince A;Godard B;Leclerc S;Sobreira N;Ling H;Awadalla P;Thibeault M;Khairy P;MIBAVA Leducq consortium;Samuels ME;Andelfinger G
• 通讯作者: Andelfinger G

Clinical and molecular evaluation of 13 Brazilian patients with Gomez-López-Hernández syndrome.

13 名巴西戈麦斯-洛佩斯-埃尔南德斯综合征患者的临床和分子评估。

• DOI: 10.1002/ajmg.a.62059
• 发表时间: 2021
• 期刊: American journal of medical genetics. Part A
• 作者: Perrone,Eduardo;Perez,AnaBeatrizAlvarez;D'Almeida,Vânia;deMello,ClaudiaBerlim;Jacobina,MarcelaAmaralAvelino;Loureiro,RafaelMaffei;Burlin,Stênio;Migliavacca,Michele;doAmaralVirmond,Luiza;Graziadio,Carla;Pedroso,JoséLuiz;Mend
• 通讯作者: Mend

New tools for Mendelian disease gene identification: PhenoDB variant analysis module; and GeneMatcher, a web-based tool for linking investigators with an interest in the same gene.

• DOI: 10.1002/humu.22769
• 发表时间: 2015-04
• 期刊: Human mutation
• 影响因子: 3.9
• 作者: Sobreira N;Schiettecatte F;Boehm C;Valle D;Hamosh A
• 通讯作者: Hamosh A