University of Washington Mendelian Genomics Research Center (UW-MGRC)
华盛顿大学孟德尔基因组学研究中心 (UW-MGRC)
基本信息
- 批准号:10215884
- 负责人:
- 金额:$ 270.13万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-06-01 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:CRISPR interferenceClinVarClinicalClustered Regularly Interspaced Short Palindromic RepeatsCodeCommunitiesCongenital AbnormalityConiferophytaCountryCoupledDataData Coordinating CenterDepositionDevelopmentDiagnosticDiagnostic testsDiseaseFURIN geneFamilyGene ExpressionGenesGeneticGenomeGenomicsGenotypeGoalsHuman GeneticsIndividualIndustryInstitutesInstitutionKnowledgeLeadershipLinkMedicalMedical GeneticsMetadataMethodologyMethodsMutationNational Heart, Lung, and Blood InstituteNational Human Genome Research InstituteOncogenesOnline SystemsOpen Reading FramesPathogenicityPhenotypePublishingRNA SplicingRare DiseasesReportingResearchResearch PersonnelRoleSamplingStructureTechnologyTestingTranslationsUnited States National Institutes of HealthUniversitiesUntranslated RNAValidationVariantWashingtonWorkadvocacy organizationsanalytical toolbaseclinical carecohortcost effectivedata resourcedata sharingdata toolsdatabase of Genotypes and Phenotypesdesignexomeexome sequencingfollow-upgene discoverygenetic architecturegenome analysisgenome editinggenome sequencinggenome wide methylationhigh throughput screeninginnovationnext generation sequencingnovelnovel strategiesopen dataphenotypic dataprogramsrare conditionrepositorysuccesstechnological innovationtooltranscriptome sequencingwhole genome
项目摘要
PROJECT SUMMARY/ABSTRACT
The genetic basis of >2,920 Mendelian conditions (MCs) remains unknown, and hundreds of novel MCs are
described each year. Our group has, in partnership with 2,379 investigators from 656 institutions in 55 countries,
assessed 15,387 samples from 5,675 families and has, over the past decade, identified genes for 1379 MCs,
including 915 novel discoveries. The translation and impact of these discoveries on diagnostics and clinical care
has been immediate and substantial. Additionally, we have developed multiple new analytical tools including
CADD, PRIMUS, CoNIFER, SMRT-SV, RV-TDT, as well as methodological innovations including MIPs, smMIPs,
and approaches for low input exome and genome sequencing (ES/WGS). We are also deeply committed to open
data sharing with rolling submission of exome and genome data to the AnVIL (1,439 deposited); development of
a MatchMaker Exchange node (http://MyGene2.org) that enables public sharing of genotype and phenotypic
data among families, researchers, and clinicians; and creation of a public data browser
(http://geno2mp.gs.washington.edu) that links de-identified, individual-level genotypes from over 18,000
exomes/genomes to individual phenotypes. In this application, we build upon these successes to establish the
University of Washington Mendelian Genomics Research Center (UW-MGRC) with the overarching goal to
maximize novel gene discovery for MCs, with an emphasis on canonical MCs that have gone unsolved using
ES/WGS, and noncoding variants underlying MCs. To this end, we will develop novel approaches to inform
variant interpretation and functional validation for the human genetics community at-large and disseminate
results, data, and tools openly. We will capitalize on immediate access to sequence-ready samples from ~300
MCs (>26,000 samples), 1,500 samples suspected of harboring a causal noncoding variant for a MC, and an
aggressive sample solicitation plan in partnership with industry, academic centers, and other NIH programs. We
propose three specific aims: (1) maximize novel gene discovery for MCs by solicitation, sequencing, and analysis
of families with unexplained (i.e., no known underlying gene) MCs; classic MCs considered high priority by the
clinical genetics community and that have been recalcitrant to gene discovery efforts; and cases that remain
unsolved after prior exome or genome sequencing. (2) Develop new strategies for gene discovery for unsolved
MCs caused by variants that are difficult to detect or of unknown functional effects (e.g., structural variants,
repeat expansions, cryptic splice, regulatory, etc.), and/or unusual modes of inheritance, and, in doing so,
characterize the genetic architecture of pathogenic noncoding variants underlying MCs. Implement high-
throughput screening and targeted follow-up functional studies to prioritize and validate assertions of
pathogenicity of candidate noncoding variants. (3) Take a leadership role to openly and publicly, when feasible,
share sequencing and rich phenotypic metadata, methods, and knowledge, to empower investigators worldwide
and accelerate the pace of gene discovery.
项目总结/摘要
超过2,920种孟德尔病症(MC)的遗传基础仍然未知,数百种新的MC正在研究中。
每年描述。我们的团队与来自55个国家656个机构的2,379名研究人员合作,
评估了来自5,675个家庭的15,387个样本,在过去的十年中,确定了1379个MC的基因,
其中包括915项新发现。这些发现对诊断和临床护理的转化和影响
是即时的和实质性的。此外,我们还开发了多种新的分析工具,包括
CADD、PRIMUS、CoNIFER、SMRT-SV、RV-TDT以及包括MIP、smMIP、
以及用于低输入外显子组和基因组测序(ES/WGS)的方法。我们也致力于开放
通过向AnVIL滚动提交外显子组和基因组数据(1,439个已保存)实现数据共享;
一个MatchMaker Exchange节点(http:MyGene2.org),用于公开共享基因型和表型
家庭、研究人员和临床医生之间的数据;以及创建公共数据浏览器
(http:geno2mp.gs.washington.edu),该网站将来自18,000多个国家的去识别化的个人基因型联系起来,
外显子组/基因组与个体表型的关系。在这个应用程序中,我们建立在这些成功的基础上,
华盛顿大学孟德尔基因组学研究中心(UW-MGRC)的总体目标是
最大限度地为MC发现新的基因,重点是使用未解决的典型MC
ES/WGS和MC基础的非编码变体。为此,我们将开发新的方法,
为人类遗传学界提供变异解释和功能验证,
结果、数据和工具。我们将利用从约300个样本中立即获得测序样本的机会,
MC(> 26,000个样品),1,500个怀疑携带MC的因果非编码变体的样品,和1,500个怀疑携带MC的因果非编码变体的样品。
积极的样品征集计划与行业,学术中心和其他NIH计划合作。我们
提出了三个具体目标:(1)通过征集、测序和分析,最大限度地发现MC的新基因
无法解释的家庭(即,没有已知的潜在基因)MC;经典MC被认为是高优先级的
临床遗传学界和已被拒绝的基因发现的努力;和案件仍然存在
在先前的外显子组或基因组测序之后未解决。(2)为未解决的基因发现开发新策略
由难以检测的变体或未知功能效应(例如,结构变体,
重复扩增、隐蔽剪接、调节等),和/或不寻常的遗传方式,这样做,
表征致病性非编码变异体的遗传结构的MC。实施高-
通量筛选和有针对性的后续功能研究,以优先考虑和验证以下断言:
候选非编码变体的致病性。(3)在可行的情况下,发挥领导作用,
共享测序和丰富的表型元数据、方法和知识,以增强全球研究者的能力
并加快基因发现的步伐。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
MICHAEL Joseph BAMSHAD其他文献
MICHAEL Joseph BAMSHAD的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('MICHAEL Joseph BAMSHAD', 18)}}的其他基金
University of Washington Mendelian Genomics Research Center (UW-MGRC)
华盛顿大学孟德尔基因组学研究中心 (UW-MGRC)
- 批准号:
10415070 - 财政年份:2021
- 资助金额:
$ 270.13万 - 项目类别:
University of Washington Mendelian Genomics Research Center (UW-MGRC)
华盛顿大学孟德尔基因组学研究中心 (UW-MGRC)
- 批准号:
10612917 - 财政年份:2021
- 资助金额:
$ 270.13万 - 项目类别:
Genetic and Molecular Basis of Congenital Contractures
先天性挛缩的遗传和分子基础
- 批准号:
7982492 - 财政年份:2010
- 资助金额:
$ 270.13万 - 项目类别: