Retrotransposition in Health and Disease
健康与疾病中的逆转录转座
基本信息
- 批准号:9105045
- 负责人:
- 金额:$ 53.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-05-01 至 2020-03-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAffectAlternative SplicingBarrett EsophagusBiological AssayBiological MarkersBloodBrainCancer EtiologyCancer cell lineCarcinomaCell Culture TechniquesCell LineCellsCodeColon AdenocarcinomaColorectalDNADataDevelopmentDiseaseEpithelialEventExonsFosteringFrequenciesGene ExpressionGenesGenetic RecombinationGenomicsGerm LinesHealthHistocompatibility TestingHumanHuman GenomeIndiumInsertion MutationLesionMalignant NeoplasmsMalignant neoplasm of esophagusMalignant neoplasm of gastrointestinal tractMetaplasiaMindMusNeoplasm MetastasisNested PCRNormal CellNormal tissue morphologyOrganPancreasPaste substancePatientsPhenotypePlayPoint MutationPolyadenylationPolypsPremalignantPrimary NeoplasmProcessRNA FoldingReportingRetrotranspositionRetrotransposonRiskRoleSerumSignal TransductionSiteSolid NeoplasmSomatic CellTechniquesTestingTimeTissuescarcinogenesisneoplastic cellneural precursor cellnoveloutcome forecastprematurepromoterpublic health relevancesingle cell sequencingtransposon/insertion elementtumortumor DNAtumor progressiontumor xenografttumorigenesis
项目摘要
DESCRIPTION (provided by applicant)
Although we used to believe that all retrotransposition occurred in the germ line in humans, over the past 10 years it has become clear that somatic retrotransposition, especially of LINE1s (L1s), is prominent, at least in the brain and in epithelial cancers. A number of groups have shown retrotransposition in neural precursor cells and the adult brain. Likewise, a number of groups including our own have shown significant retrotransposition in gastrointestinal cancers. A key finding of our studies is that most L1 insertions in GI cancers occur very early in cancer development. Indeed, some of the insertions are found in low concentration (detected only by nested PCR) in normal cells, but they become essentially clonal in the cancer (detected by conventional PCR). ln this application, we strive to answer two big questions in the field. First, does significant retrotransposition occur in adult somatic tissues outside of the brain and, if so,
at what frequency? In this aim we will study L1 insertions in single normal cells near the tumors to find what fraction of the insertions in the tumor are already present in normal cells. We will determine if retrotransposition rate is greater in normal cells or in tumor cells. We will also stuy the frequency of insertions in single normal cells not associated with cancer and from various organs to determine if some tissue types have a greater propensity for retrotransposition than others. The second big question is: Does L1 somatic retrotransposition have any significant role in the etiology of cancer? We need to determine whether we can alter the cellular phenotype towards normal by deletion of somatic L1 insertions found in cancer-related genes in cancer-derived cell lines.
描述(由申请人提供)
尽管我们过去认为所有的逆转录转座都发生在人类的生殖系中,但在过去的10年里,体细胞逆转录转座,特别是LINE1(L1s)的逆转座,已经变得明显,至少在大脑和上皮性癌症中是如此。许多研究小组已经在神经前体细胞和成人大脑中显示出逆转位。同样,包括我们自己在内的许多组在胃肠道癌症中显示出显著的逆转位。我们研究的一个关键发现是,大多数胃肠道癌症的L1插入发生在癌症发展的非常早期。事实上,在正常细胞中发现了一些低浓度的插入片段(仅通过套式聚合酶链式反应检测到),但在癌症中它们基本上变成了克隆(通过传统的聚合酶链式反应检测到)。在这项申请中,我们努力回答该领域的两个大问题。首先,在大脑以外的成人躯体组织中是否发生了显著的逆转位,如果是的话,
频率是多少?在这个目标中,我们将研究肿瘤附近单个正常细胞中的L1插入,以找出正常细胞中已经存在的肿瘤中插入的部分。我们将确定在正常细胞和肿瘤细胞中逆转录转座率哪个更高。我们还将研究单个与癌症无关的正常细胞和来自不同器官的插入频率,以确定是否某些组织类型比其他组织类型有更大的逆转位倾向。第二个大问题是:L1体细胞逆转位在癌症的病因学中有任何重要作用吗?我们需要确定是否可以通过删除在癌症相关基因中发现的体细胞L1插入来将细胞表型转变为正常。
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 }}
HAIG H. KAZAZIAN其他文献
Molecular Size Studies on 6-Phosphogluconate Dehydrogenase
6-磷酸葡萄糖酸脱氢酶的分子大小研究
- DOI:
10.1038/212197a0 - 发表时间:
1966-10-08 - 期刊:
- 影响因子:48.500
- 作者:
HAIG H. KAZAZIAN - 通讯作者:
HAIG H. KAZAZIAN
Identity of different mutations for deleterious genes (reply)
有害基因不同突变的特性(回复)
- DOI:
10.1038/301176b0 - 发表时间:
1983-01-13 - 期刊:
- 影响因子:48.500
- 作者:
HAIG H. KAZAZIAN;ARAVINDA CHAKRAVARTI;STUART H. ORKIN - 通讯作者:
STUART H. ORKIN
HAIG H. KAZAZIAN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('HAIG H. KAZAZIAN', 18)}}的其他基金
The role of retrotransposons in autism spectrum disorders
逆转录转座子在自闭症谱系障碍中的作用
- 批准号:
8046942 - 财政年份:2010
- 资助金额:
$ 53.25万 - 项目类别:
Augmenting GWAS with Retrotransposon Polymorphisms
利用逆转录转座子多态性增强 GWAS
- 批准号:
7811559 - 财政年份:2009
- 资助金额:
$ 53.25万 - 项目类别:
Augmenting GWAS with Retrotransposon Polymorphisms
利用逆转录转座子多态性增强 GWAS
- 批准号:
7943987 - 财政年份:2009
- 资助金额:
$ 53.25万 - 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:
$ 53.25万 - 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:
$ 53.25万 - 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:
$ 53.25万 - 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:
$ 53.25万 - 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:
$ 53.25万 - 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:
$ 53.25万 - 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:
$ 53.25万 - 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:
$ 53.25万 - 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:
$ 53.25万 - 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:
$ 53.25万 - 项目类别:
Grant-in-Aid for Early-Career Scientists