Systematic in vivo characterization of disease-associated regulatory variants
疾病相关调控变异的系统体内表征
基本信息
- 批准号:10472058
- 负责人:
- 金额:$ 184.86万
- 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:2021-09-01 至 2026-05-31
- 项目状态:未结题
- 来源:
- 关键词:AchievementAffectAlgorithmsAllelesBar CodesBiological AssayBlood CirculationBrainCatalogsCellsClinical ResearchCodeCommunitiesComplexControlled StudyDNADataData CollectionDiseaseEnvironmentExhibitsFemaleFrequenciesFutureGene ExpressionGene Expression RegulationGenesGeneticGenetic VariationGenetic studyGenomic SegmentGenomicsGoalsHealthHeartHeterogeneityHumanHuman GeneticsIndividualInflammatoryLeadLibrariesLinkLiverLungMeasurementMusMuscleOrganPhysiologicalPhysiologyPositioning AttributeProcessProtocols documentationRNA SequencesRare DiseasesRegulator GenesRegulatory ElementReporterReportingResearch PersonnelSignal TransductionTestingTissuesTranscriptional RegulationUntranslated RNAValidationVariantViralWorkadeno-associated viral vectorbasecell typedisorder riskexperimental studygene environment interactiongenetic variantgenome wide association studygenomic locusgenomic variationhuman genomicsin vivomalemembernetwork modelsnew therapeutic targetprediction algorithmpredictive modelingpublic health relevancerisk variantsextraittranscription factor
项目摘要
ABSTRACT
Thousands of genetic loci are associated with human traits or disease risk, and these loci each typically contain
tens to hundreds of variants, most of which are non-coding and lack direct evidence of effects on genes.
Experimental tests of genomic variants are needed to identify functional effects, which can be specific to one
sex, tissue, and/or perturbed environmental context. Testing effects of risk variants on gene regulation requires
an ability to quantify the potentially modest consequences of thousands of alleles in a carefully controlled study.
Our overarching goal is to systematically characterize the impact of human genetic variation on gene regulation
via massively parallel reporter assays (MPRA). We will select variants based primarily on genome-wide
association studies (GWAS) for common diseases and complex traits relevant to the brain, liver, lung, muscle,
and/or heart. We will examine all plausible functional candidates at prioritized GWAS loci to provide data for tests
of regulatory variant prediction algorithms, positive control variants, and variants prioritized based on regulatory
element annotations. The gene regulatory effect of ~500,000 variant alleles will be interrogated in five organs
(brain, liver, lung, muscle and heart) using systemic circulation of adeno-associated viral (AAV) MPRA libraries.
We will repeat this experiment in a perturbed inflammatory state to evaluate gene-environment interactions. As
a result, we will comprehensively characterize variant effects on regulatory function by analyses of variants in
the physiological conditions of multiple tissues, in both sexes, with and without perturbation typical of disease
environments. Selected variants will be edited into human pluripotent cells for validation. As members of the
Impact of Genomic Variation on Function (IGVF) Consortium, we will generate a regulatory variant catalog for
the community, and enable future studies through data collection and predictive models. Successful completion
of these aims will provide ~10 million allelic effect data points that encompass tissue-, sex-, and perturbation-
specific regulatory effects. We will work with the IGVF consortium to finalize selection of variants, organs, and
perturbations to generate a comprehensive catalog. The expertise of the study investigators in GWAS, statistical
and computational genetics, human genomics, AAV delivery, and mouse physiology make achievement of these
aims feasible and likely highly informative to understand how genomic variation impacts human health and
disease.
摘要
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 Isaiah Love其他文献
Michael Isaiah Love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 Isaiah Love', 18)}}的其他基金
Systematic in vivo characterization of disease-associated regulatory variants
疾病相关调控变异的系统体内表征
- 批准号:
10296745 - 财政年份:2021
- 资助金额:
$ 184.86万 - 项目类别:
Systematic in vivo characterization of disease-associated regulatory variants
疾病相关调控变异的系统体内表征
- 批准号:
10631225 - 财政年份:2021
- 资助金额:
$ 184.86万 - 项目类别:
A Modular Framework for Accurate, Efficient, and Reproducible Analysis of RNA-Seq Data
用于准确、高效和可重复分析 RNA-Seq 数据的模块化框架
- 批准号:
10170579 - 财政年份:2020
- 资助金额:
$ 184.86万 - 项目类别:
A Modular Framework for Accurate, Efficient, and Reproducible Analysis of RNA-Seq Data
用于准确、高效和可重复分析 RNA-Seq 数据的模块化框架
- 批准号:
10238765 - 财政年份:2020
- 资助金额:
$ 184.86万 - 项目类别:
A Modular Framework for Accurate, Efficient, and Reproducible Analysis of RNA-Seq Data
用于准确、高效和可重复分析 RNA-Seq 数据的模块化框架
- 批准号:
10440402 - 财政年份:2020
- 资助金额:
$ 184.86万 - 项目类别:
pathQTL: Integrative Multi-Omics Causal Inference of Molecular Mechanisms Leading to Neuropsychiatric Illness
pathQTL:导致神经精神疾病的分子机制的综合多组学因果推断
- 批准号:
10318952 - 财政年份:2018
- 资助金额:
$ 184.86万 - 项目类别:
pathQTL: Integrative Multi-Omics Causal Inference of Molecular Mechanisms Leading to Neuropsychiatric Illness
pathQTL:导致神经精神疾病的分子机制的综合多组学因果推断
- 批准号:
10550143 - 财政年份:2018
- 资助金额:
$ 184.86万 - 项目类别:
pathQTL: Integrative Multi-Omics Causal Inference of Molecular Mechanisms Leading to Neuropsychiatric Illness
pathQTL:导致神经精神疾病的分子机制的综合多组学因果推断
- 批准号:
10066367 - 财政年份:2018
- 资助金额:
$ 184.86万 - 项目类别:
相似海外基金
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 184.86万 - 项目类别:
Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 184.86万 - 项目类别:
Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 184.86万 - 项目类别:
Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 184.86万 - 项目类别:
Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 184.86万 - 项目类别:
Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 184.86万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 184.86万 - 项目类别:
Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
- 批准号:
2301846 - 财政年份:2023
- 资助金额:
$ 184.86万 - 项目类别:
Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 184.86万 - 项目类别:
Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
- 批准号:
23K16076 - 财政年份:2023
- 资助金额:
$ 184.86万 - 项目类别:
Grant-in-Aid for Early-Career Scientists














{{item.name}}会员




