Multiscale functional characterization of genomic variation in human developmental disorders

人类发育障碍基因组变异的多尺度功能表征

基本信息

  • 批准号:
    10689051
  • 负责人:
  • 金额:
    $ 195.93万
  • 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

项目摘要

Project Summary/Abstract Large-scale studies have identified thousands of genetic variants linked to developmental defects, together with the regulatory elements harboring these variants and the cell types in which these variants likely function. This diversity of variants, regulatory elements, and cell types indicates that multiple mechanisms contribute to developmental defects. One key challenge to our understanding of these mechanisms is that the molecular, cellular, and functional phenotypes of each variant remain largely uncharacterized. Until these critical gaps in knowledge are addressed, the underlying molecular and cellular determinants of developmental disease susceptibility will remain incomplete. To bridge these gaps, we propose to establish the “UT Southwestern Center for Regulatory Element Variation and Function”. The primary goal of this Center is to systematically catalog molecular and cellular phenotypes for disease-associated enhancers in human development, with a focus on gaining insights into mechanisms of non-canonical human genetics and gene regulation. To build a generalizable framework to understanding the impact of human genetic variation on function, we propose a high throughput perturbation platform with three primary goals: (1) Contribute to a variant/element/phenotype catalog with relevance to diseases of human development, focusing on elements genetically associated with congenital heart disease (cardiomyocytes), autism (neurons), and placental defects (trophoblasts); (2) Contribute to a variant/element/phenotype catalog for non-canonical human genetics, focusing on two understudied topics in human genetics: pleiotropic effects and non-cell autonomous effects; and (3) Contribute to a variant/element/phenotype catalog with relevance to mechanisms of gene regulation, focusing on enhancer RNAs. The Center will take advantage of recent technological innovations in genome engineering, single-cell genomics, and high content screening to enable the multiscale functional characterization of genomic variation in human developmental disorders. Several of these techniques have been pioneered by investigators contributing to this project, including: the development of novel tools for enhancer perturbation and the coupling of endogenous enhancer perturbations with a single-cell RNA-Seq readout (Mosaic-Seq). Impact and Significance: The efforts on this project will lead to a number of key outcomes and deliverables, including (1) greater understanding of the relationships between sequence variation and genome function, (2) an extensive variant/element/phenotype catalog for the community, (3) tools for generating predictive models for the community, and (4) resources to enable future functional genomics studies. Together, our multifaceted and combinatorial approaches will open new horizons to understanding the impact of regulatory variants on developmental disease phenotypes.
项目总结/文摘

项目成果

期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Single-Cell Genomics: Catalyst for Cell Fate Engineering.
Computational identification of clonal cells in single-cell CRISPR screens.
  • DOI:
    10.1186/s12864-022-08359-1
  • 发表时间:
    2022-02-15
  • 期刊:
  • 影响因子:
    4.4
  • 作者:
    Wang Y;Xie S;Armendariz D;Hon GC
  • 通讯作者:
    Hon GC
Enhancer regulatory networks globally connect non-coding breast cancer loci to cancer genes.
增强子调控网络在全球范围内将非编码乳腺癌基因座与癌症基因连接起来。
  • DOI:
    10.1101/2023.11.20.567880
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Wang,Yihan;Armendariz,Daniel;Wang,Lei;Zhao,Huan;Xie,Shiqi;Hon,GaryC
  • 通讯作者:
    Hon,GaryC
Breaking enhancers to gain insights into developmental defects.
  • DOI:
    10.7554/elife.88187
  • 发表时间:
    2023-07-27
  • 期刊:
  • 影响因子:
    7.7
  • 作者:
    Armendariz DA;Sundarrajan A;Hon GC
  • 通讯作者:
    Hon GC
{{ 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 }}

Gary Chung Hon其他文献

Gary Chung Hon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('Gary Chung Hon', 18)}}的其他基金

Systematic Assessment of Combinatorial Transcription Factor Activity
组合转录因子活性的系统评估
  • 批准号:
    10897439
  • 财政年份:
    2023
  • 资助金额:
    $ 195.93万
  • 项目类别:
Determinants of Cell State Reprogramming
细胞状态重编程的决定因素
  • 批准号:
    10626919
  • 财政年份:
    2022
  • 资助金额:
    $ 195.93万
  • 项目类别:
Determinants of Cell State Reprogramming
细胞状态重编程的决定因素
  • 批准号:
    10406224
  • 财政年份:
    2022
  • 资助金额:
    $ 195.93万
  • 项目类别:
Multiscale functional characterization of genomic variation in human developmental disorders
人类发育障碍基因组变异的多尺度功能表征
  • 批准号:
    10296634
  • 财政年份:
    2021
  • 资助金额:
    $ 195.93万
  • 项目类别:
Multiscale functional characterization of genomic variation in human developmental disorders
人类发育障碍基因组变异的多尺度功能表征
  • 批准号:
    10473897
  • 财政年份:
    2021
  • 资助金额:
    $ 195.93万
  • 项目类别:
Combinatorial Biology of Gene Regulation for Cellular Engineering
细胞工程基因调控的组合生物学
  • 批准号:
    10372278
  • 财政年份:
    2017
  • 资助金额:
    $ 195.93万
  • 项目类别:
Combinatorial Biology of Gene Regulation for Cellular Engineering
细胞工程基因调控的组合生物学
  • 批准号:
    9349247
  • 财政年份:
    2017
  • 资助金额:
    $ 195.93万
  • 项目类别:

相似海外基金

EXCESS: The role of excess topography and peak ground acceleration on earthquake-preconditioning of landslides
过量:过量地形和峰值地面加速度对滑坡地震预处理的作用
  • 批准号:
    NE/Y000080/1
  • 财政年份:
    2024
  • 资助金额:
    $ 195.93万
  • 项目类别:
    Research Grant
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
  • 批准号:
    2328975
  • 财政年份:
    2024
  • 资助金额:
    $ 195.93万
  • 项目类别:
    Continuing Grant
SHINE: Origin and Evolution of Compressible Fluctuations in the Solar Wind and Their Role in Solar Wind Heating and Acceleration
SHINE:太阳风可压缩脉动的起源和演化及其在太阳风加热和加速中的作用
  • 批准号:
    2400967
  • 财政年份:
    2024
  • 资助金额:
    $ 195.93万
  • 项目类别:
    Standard Grant
Market Entry Acceleration of the Murb Wind Turbine into Remote Telecoms Power
默布风力涡轮机加速进入远程电信电力市场
  • 批准号:
    10112700
  • 财政年份:
    2024
  • 资助金额:
    $ 195.93万
  • 项目类别:
    Collaborative R&D
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
  • 批准号:
    2328973
  • 财政年份:
    2024
  • 资助金额:
    $ 195.93万
  • 项目类别:
    Continuing Grant
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
  • 批准号:
    2328972
  • 财政年份:
    2024
  • 资助金额:
    $ 195.93万
  • 项目类别:
    Continuing Grant
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
  • 批准号:
    2328974
  • 财政年份:
    2024
  • 资助金额:
    $ 195.93万
  • 项目类别:
    Continuing Grant
Collaborative Research: A new understanding of droplet breakup: hydrodynamic instability under complex acceleration
合作研究:对液滴破碎的新认识:复杂加速下的流体动力学不稳定性
  • 批准号:
    2332916
  • 财政年份:
    2024
  • 资助金额:
    $ 195.93万
  • 项目类别:
    Standard Grant
Collaborative Research: A new understanding of droplet breakup: hydrodynamic instability under complex acceleration
合作研究:对液滴破碎的新认识:复杂加速下的流体动力学不稳定性
  • 批准号:
    2332917
  • 财政年份:
    2024
  • 资助金额:
    $ 195.93万
  • 项目类别:
    Standard Grant
Study of the Particle Acceleration and Transport in PWN through X-ray Spectro-polarimetry and GeV Gamma-ray Observtions
通过 X 射线光谱偏振法和 GeV 伽马射线观测研究 PWN 中的粒子加速和输运
  • 批准号:
    23H01186
  • 财政年份:
    2023
  • 资助金额:
    $ 195.93万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了