Baylor-Johns Hopkins Center for Mendelian Genetics

贝勒-约翰霍普金斯孟德尔遗传学中心

基本信息

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
项目类别：
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

项目摘要

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.

尽管识别负责孟德尔疾病的基因和变体的生物学和医学价值非常高，但其中绝大多数在分子水平上仍然无法解释。为此，我们将在该国的两个最古老，最有成就的人类遗传学计划，贝勒医学院（BCM）和约翰·霍普金斯大学医学院（JHUSOM）之间建立伙伴关系，以组成Mendelian Genomics（BHCMG）的Baylor-Hopkins中心。在此过程中，我们将通过结合我们在临床遗传学，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我们完全访问OMIM和提供的协同作用。我们将通过创建和利用全球范围内的同事和前学员网络来识别和招募成千上万的患者和具有无法解释的门德尔表型的患者和家庭，或者患有无法诊断的疾病来识别和招募，他们的挑战是找到和招募代表这些罕见疾病的样本的挑战，或者招募了成千上万的患者和家庭，或者患有无法诊断的疾病，这些疾病在其家庭中占据了Mendelian Traits。在我们的两个机构中，我们已经有> 2,000个DNA样品，并且已经在全球17名合作者网络中确定了> 12,000个DNA样本。此外，我们制定了利用OMIM（> 10，000次独特的命中/天）来标记无法解释的表型和招募样品的策略。我们将通过建立一个通过OMIM以及通过BHCMG网站访问并访问的样本和疾病跟踪数据库来进一步组织我们的努力，并组建了一个专家委员会，以协助解决不可避免的ELSI问题。我们将建立在现有的高通量基因分型和测序管道的基础上，以开发集成的实验室工作，我们将使用来自两个机构以及外部专家的专家委员会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OMIM和其他基于Web的资源的积极数据传播计划，并组织年度孟德尔遗传学会议，向所有人开放。

项目成果

期刊论文数量（41）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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.

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

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

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
影响因子：
0
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

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

New Arab family with cerebral dysgenesis, neuropathy, ichthyosis and keratoderma syndrome suggests a possible founder effect for the c.223delG mutation.