Exploring the Genomic Dark Matter of Neurodevelopmental Disorders

探索神经发育障碍的基因组暗物质

基本信息

项目摘要

SUMMARY Neurodevelopmental disorders (NDDs) comprise of a group of disorders associated with abnormal brain development. NDDs with intellectual disability (ID), characterized by significant limitations in intellectual functioning and adaptive behavior, affect 1% of the population globally and pose a significant public health burden on society. The underlying neuronal mechanisms of dysregulation that trigger NDD onset and progression are not fully understood. Rare genetic variants have been shown to play a key role in their development, especially in those NDDs which are severe in nature. During the last decade, genetic testing has emerged as an important etiological diagnostic test for NDDs with a considerable impact on disease management and treatment. Yet, current genetic testing has a diagnostic rate of ~ 50%. Due to technical limitations in modern next-generation sequencing techniques, these techniques fail to asses a large part of the genome (2/3rd), missing critical regions which may have clinical significance. New methods now have emerged that can assess these regions (i.e. the genomic dark matter) better, can access repetitive regions and identify complex structural genomic events with more accuracy. As such, we hypothesize that a large fraction of genetic variation involved in the etiology of NDDs remains undetected by current sequencing techniques. It is imperative to characterize the spectrum of genomic variants that remain undetected in NDDs to improve diagnostic detection methods. Our goal is two adopt two new cost- effective technologies, i.e. Optical Genome Mapping (OGM) and Single Tube Long Fragment Reads sequencing (stLFR), to identify the underlying genetic cause in 50 genetically unsolved families with severe NDDs including ID. These families were previously investigated using standard short-read sequencing technologies with inconclusive results. Combining both stLFR and OGM will provide an enhanced overview of genomic variation in difficult to diagnose cases, including clinically significant genomic variation. This project is a pilot project aimed to better understand the genomic landscape of variants associated with aberrant neurodevelopment and cognition. Our current understanding of the human genome is still limited due to restrictions in technologies, and these results will lay the foundation for a larger scale study which will eventually improve genetic diagnostic screening and patient management.
摘要 神经发育障碍(NDDS)由一组与异常大脑相关的疾病组成 发展。有智力残疾(ID)的非智力发展障碍,其特点是智力严重受限 功能和适应行为,影响全球1%的人口,并构成重大公共健康 给社会带来负担。触发NDD发生和发展的调节失调的潜在神经机制 进展还没有完全被理解。罕见的基因变异已被证明在它们的 发展,特别是在那些性质严重的国家发展中。在过去的十年里,基因检测已经 作为一种重要的NDDS病因学诊断试验,对疾病有相当大的影响 管理和治疗。然而,目前的基因检测的诊断率约为50%。由于技术原因 现代下一代测序技术的局限性,这些技术无法评估很大一部分 基因组(2/3),缺失可能具有临床意义的关键区域。现在出现了新的方法 可以更好地评估这些区域(即基因组暗物质),可以访问重复区域并识别 更准确的复杂结构基因组事件。 因此,我们假设与NDDS病因学有关的大部分遗传变异仍然存在。 未被当前测序技术检测到的。刻画基因组变异的光谱是当务之急。 在NDDS中仍未检测到的,以改进诊断检测方法。我们的目标是两个采用两个新的成本- 有效的技术,即光学基因组作图(OGM)和单管长片段阅读序列测序 (StLFR),在50个患有严重NDD的遗传未解决的家庭中确定潜在的遗传原因,包括 这些家系之前使用标准的短读测序技术进行了研究 没有定论的结果。将stLFR和OGM结合起来将提供对基因组变异的更好的概述 在难以诊断的病例中,包括临床上显著的基因组变异。该项目是一个试点项目,旨在 为了更好地了解与神经发育异常和基因变异相关的基因组图谱 认知力。由于技术的限制,我们目前对人类基因组的了解仍然有限,而且 这些结果将为最终改进基因诊断的更大规模的研究奠定基础 筛查和病人管理。

项目成果

期刊论文数量(1)
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 }}

Isabelle Veerle Suzanne Schrauwen其他文献

Isabelle Veerle Suzanne Schrauwen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('Isabelle Veerle Suzanne Schrauwen', 18)}}的其他基金

Exploring the Genomic Dark Matter of Neurodevelopmental Disorders
探索神经发育障碍的基因组暗物质
  • 批准号:
    10452910
  • 财政年份:
    2022
  • 资助金额:
    $ 20.31万
  • 项目类别:
Unraveling the genetic architecture of cochleovestibular malformations
揭示耳蜗前庭畸形的遗传结构
  • 批准号:
    10672304
  • 财政年份:
    2022
  • 资助金额:
    $ 20.31万
  • 项目类别:
Unraveling the genetic architecture of cochleovestibular malformations
揭示耳蜗前庭畸形的遗传结构
  • 批准号:
    10522114
  • 财政年份:
    2022
  • 资助金额:
    $ 20.31万
  • 项目类别:

相似海外基金

How novices write code: discovering best practices and how they can be adopted
新手如何编写代码:发现最佳实践以及如何采用它们
  • 批准号:
    2315783
  • 财政年份:
    2023
  • 资助金额:
    $ 20.31万
  • 项目类别:
    Standard Grant
One or Several Mothers: The Adopted Child as Critical and Clinical Subject
一位或多位母亲:收养的孩子作为关键和临床对象
  • 批准号:
    2719534
  • 财政年份:
    2022
  • 资助金额:
    $ 20.31万
  • 项目类别:
    Studentship
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
  • 批准号:
    2633211
  • 财政年份:
    2020
  • 资助金额:
    $ 20.31万
  • 项目类别:
    Studentship
A material investigation of the ceramic shards excavated from the Omuro Ninsei kiln site: Production techniques adopted by Nonomura Ninsei.
对大室仁清窑遗址出土的陶瓷碎片进行材质调查:野野村仁清采用的生产技术。
  • 批准号:
    20K01113
  • 财政年份:
    2020
  • 资助金额:
    $ 20.31万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
  • 批准号:
    2436895
  • 财政年份:
    2020
  • 资助金额:
    $ 20.31万
  • 项目类别:
    Studentship
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
  • 批准号:
    2633207
  • 财政年份:
    2020
  • 资助金额:
    $ 20.31万
  • 项目类别:
    Studentship
The limits of development: State structural policy, comparing systems adopted in two European mountain regions (1945-1989)
发展的限制:国家结构政策,比较欧洲两个山区采用的制度(1945-1989)
  • 批准号:
    426559561
  • 财政年份:
    2019
  • 资助金额:
    $ 20.31万
  • 项目类别:
    Research Grants
Securing a Sense of Safety for Adopted Children in Middle Childhood
确保被收养儿童的中期安全感
  • 批准号:
    2236701
  • 财政年份:
    2019
  • 资助金额:
    $ 20.31万
  • 项目类别:
    Studentship
A Study on Mutual Funds Adopted for Individual Defined Contribution Pension Plans
个人设定缴存养老金计划采用共同基金的研究
  • 批准号:
    19K01745
  • 财政年份:
    2019
  • 资助金额:
    $ 20.31万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Structural and functional analyses of a bacterial protein translocation domain that has adopted diverse pathogenic effector functions within host cells
对宿主细胞内采用多种致病效应功能的细菌蛋白易位结构域进行结构和功能分析
  • 批准号:
    415543446
  • 财政年份:
    2019
  • 资助金额:
    $ 20.31万
  • 项目类别:
    Research Fellowships
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了