Project 1 - Genetic Predisposition To Barrett's Esophagus and Esophageal Adenocarcinoma
Project 1 - Genetic Predisposition To Barrett's Esophagus and Esophageal Adenocarcinoma
批准号:
10153702
负责人:
AMITABH CHAK
金额:
$26.05万
依托单位国家:
美国
项目类别:
财政年份:
2011
资助国家:
美国
项目状态:
已结题
起止时间:
2011-09-26 至 2023-04-30
关键词:
ATAC-seqAddressAdenocarcinomaAdhesionsAdmixtureAfrican AmericanAllelesBarrett EpitheliumBarrett EsophagusBiologicalBiological AssayChromatinClinicalCodeColumnar MetaplasiaComplexDeoxycholic AcidDevelopmentDiseaseDysplasiaElectron MicroscopyEpithelialEsophageal AdenocarcinomaEsophageal TissueEsophagitisEsophagusEtiologyEuropeanFamilyFundingGenesGeneticGenetic DeterminismGenetic EngineeringGenetic Predisposition to DiseaseGenetically Engineered MouseGerm-Line MutationHistologicHumanImpairmentKnock-outKnockout MiceLaboratoriesMapsMetaplasiaModelingMolecularMusMutant Strains MiceMutationPathogenesisPhenotypePredispositionPrevalencePrevention strategyReportingRepressionResearchResearch Project GrantsSNP genotypingSignal TransductionSquamous DifferentiationSquamous EpitheliumStratified Squamous EpitheliumSusceptibility GeneTranscriptTranslatingUntranslated RNAVariantWild Type Mouseadmixture mappingbasecohortexome sequencinggene functiongenetic variantimprovedinsightkindredlight microscopymouse modelnext generation sequencingnovelracial differenceracial disparitystomach cardiasuccessthree dimensional cell culturetreatment strategytumor progression
中文摘要
项目概要
巴雷特食管 (BE) 和食管腺癌 (EAC) 是尚未发现的复杂疾病
遗传因素。我们成功地发现了 VSIG10L 中的一个有害变异,该变异在一个大家族中分离。这个
是第一个报道的 BE 和 EAC 易感性基因。 VSIG10L 似乎在粘附和
复层鳞状上皮的分化/成熟。遗传基础的进一步线索来自我们
混合图谱研究,确定了与过量相关的两个特定染色体区域
非裔美国人有欧洲血统。因此,BETRNet 项目 1 的重点是确定
BE 和 EAC 患病率的种族差异。项目 1 的第二个 BETRNet 重点是创建一个基因
基于 VSIG10L 的工程小鼠模型,以了解从鳞状上皮到
化生巴雷特上皮。该项目现在将通过以下方式建立在这些发现的基础上:
1) 使用密集 SNP 基因分型、NextGen 测序和 ATAC-seq 来识别种族不同的遗传
解释 BE 和 EAC 患病率种族差异的变体;
2)利用基因工程VSIG10L敲除和VSIG10L S631G变体携带小鼠
了解 VSIG10L 如何促进正常鳞状上皮 食管炎 BE
化生→不典型增生→癌症进展;
项目1的意义首先是将BE和EAC种族差异的临床观察转化为
实验室确定致病遗传基础。此外,该项目将建立在我们成功发现
通过了解该基因在化生中的功能,第一个家族易感性遗传变异
Barrett 上皮细胞的转化。
英文摘要
PROJECT SUMMARY
Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) are complex diseases with undiscovered
genetic factors. We successfully discovered a deleterious variant in VSIG10L segregating in a large family. This
is the first such reported gene for susceptibility to BE and EAC. VSIG10L appears to function in adhesion and
differentiation/maturation of stratified squamous epithelium. Further clues for a genetic basis comes from our
admixture mapping study, which has identified two specific chromosomal regions associated with excess
European ancestry in African Americans. The BETRNet focus of Project 1 is thus to identify the genetic basis of
racial disparity in the prevalence of BE and EAC. A second BETRNet focus of Project 1 is to create a genetically
engineered mouse model based on VSIG10L to understand the transformation from squamous epithelium to
metaplastic Barrett's epithelium. This project will now build on these discoveries by:
1) Using dense SNP genotyping, NextGen sequencing, and ATAC-seq to identify racially disparate genetic
variants that explain racial differences in prevalence of BE and EAC;
2) Using genetically engineered VSIG10L knockout and VSIG10L S631G variant carrying mice to
understand how VSIG10L contributes to the normal squamous epithelium esophagitis BE
metaplasia dysplasia cancer progression;
The significance of Project 1 is first to translate the clinical observation of racial disparity in BE and EAC into the
laboratory to identify a causative genetic basis. Furthermore, the project will build on our successful discovery of
the first familial susceptibility genetic variant by understanding how this gene functions in metaplastic
transformation of Barrett's epithelium.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Pathways of Injury and Repair in Barrett's Carcinogenesis
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批准号:10713938
-
项目类别:
-
资助金额:$226.89万
-
财政年份:2023
-
负责人:AMITABH CHAK
-
依托单位:
Administrative Core
-
批准号:10713942
-
项目类别:
-
资助金额:$13.41万
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财政年份:2023
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负责人:AMITABH CHAK
-
依托单位:
Deciphering the Molecular Genetics of VSIG10L in Barrett's Neoplasia
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批准号:10713939
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项目类别:
-
资助金额:$54.97万
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财政年份:2023
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负责人:AMITABH CHAK
-
依托单位:
Pilot and Feasibility Program
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批准号:10361548
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项目类别:
-
资助金额:$17.59万
-
财政年份:2015
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负责人:AMITABH CHAK
-
依托单位:
Pilot and Feasibility Program
-
批准号:10555249
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项目类别:
-
资助金额:$17.59万
-
财政年份:2015
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负责人:AMITABH CHAK
-
依托单位:
GENETIC DETERMINANTS OF BARRETT'S ESOPHAGUS AND ESOPHAGEAL ADENOCARCINOMA
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批准号:9325717
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项目类别:
-
资助金额:$46.3万
-
财政年份:2011
-
负责人:AMITABH CHAK
-
依托单位:
Genetic Determinants of Barrett's Esophagus and Esophageal Adenocarcinoma
-
批准号:10153699
-
项目类别:
-
资助金额:$129.03万
-
财政年份:2011
-
负责人:AMITABH CHAK
-
依托单位:
GENETIC DETERMINANTS OF BARRETT'S ESOPHAGUS AND ESOPHAGEAL ADENOCARCINOMA
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批准号:8546709
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项目类别:
-
资助金额:$126.84万
-
财政年份:2011
-
负责人:AMITABH CHAK
-
依托单位:
GENETIC DETERMINANTS OF BARRETT'S ESOPHAGUS AND ESOPHAGEAL ADENOCARCINOMA
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批准号:8918503
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项目类别:
-
资助金额:$144.66万
-
财政年份:2011
-
负责人:AMITABH CHAK
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依托单位:
Genetic Determinants of Barrett's Esophagus and Esophageal Adenocarcinoma
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批准号:9276253
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项目类别:
-
资助金额:$135.63万
-
财政年份:2011
-
负责人:AMITABH CHAK
-
依托单位:
Genetic Determinants of Barrett's Esophagus and Esophageal Adenocarcinoma
-
批准号:9918849
-
项目类别:
-
资助金额:$128.92万
-
财政年份:2011
-
负责人:AMITABH CHAK
-
依托单位:
Whole Exome Approaches for Esophageal Adenocarcinoma Susceptibility Genes
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批准号:8555511
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项目类别:
-
资助金额:$25.08万
-
财政年份:2011
-
负责人:AMITABH CHAK
-
依托单位:
GENETIC DETERMINANTS OF BARRETT'S ESOPHAGUS AND ESOPHAGEAL ADENOCARCINOMA
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批准号:8721883
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项目类别:
-
资助金额:$142.47万
-
财政年份:2011
-
负责人:AMITABH CHAK
-
依托单位:
Project 3: Molecular Markers for Early Detection of Esophageal Carcinogenesis
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批准号:10227754
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项目类别:
-
资助金额:$23.25万
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财政年份:2011
-
负责人:AMITABH CHAK
-
依托单位:
Administrative Core
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批准号:8555517
-
项目类别:
-
资助金额:$8.43万
-
财政年份:2011
-
负责人:AMITABH CHAK
-
依托单位:
Genetic Determinants of Barrett's Esophagus and Esophageal Adenocarcinoma
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批准号:10605426
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项目类别:
-
资助金额:$50.48万
-
财政年份:2011
-
负责人:AMITABH CHAK
-
依托单位:
Administrative Core
-
批准号:10153701
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项目类别:
-
资助金额:$7.94万
-
财政年份:2011
-
负责人:AMITABH CHAK
-
依托单位:
GENETIC DETERMINANTS OF BARRETT'S ESOPHAGUS AND ESOPHAGEAL ADENOCARCINOMA
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批准号:8209773
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项目类别:
-
资助金额:$102.63万
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财政年份:2011
-
负责人:AMITABH CHAK
-
依托单位:
GENETIC DETERMINANTS OF BARRETT'S ESOPHAGUS AND ESOPHAGEAL ADENOCARCINOMA
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批准号:8338823
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项目类别:
-
资助金额:$117.44万
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财政年份:2011
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负责人:AMITABH CHAK
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依托单位:
CONSORTIUM TO IDENTIFY GENES FOR BARRETT'S ESOPHAGUS
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批准号:8171722
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项目类别:
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资助金额:$0.99万
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财政年份:2010
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负责人:AMITABH CHAK
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依托单位:
海外基金