Characterizing the Human Imprint Regulatory Regions Associated with Childhood Obesity
表征与儿童肥胖相关的人类印记调节区域
基本信息
- 批准号:10662238
- 负责人:
- 金额:$ 56.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-06 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:5 year oldAdolescentAffectAgeAgingAlgorithmsAllelesBinding SitesBioinformaticsBiological AssayBirthBlood CellsBrainCell AgingCell Differentiation processCellsCharacteristicsChildChildhoodChromatin StructureConceptusCpG IslandsCpG dinucleotideCuesCytosineDNADNA MethylationDataDatabasesDeoxyribonucleasesDepositionDesire for foodDevelopmentDiseaseElementsEmbryoEmbryonic DevelopmentEndodermEnvironmental ExposureEpigenetic ProcessEtiologyFailureFatty acid glycerol estersFemaleFundingGene ClusterGene ExpressionGenerationsGenesGeneticGenetic PolymorphismGenomic ImprintingGerm LayersGoalsGrowthGrowth DisordersHealthHumanHuman GenomeIndividualKidneyLifeLife Cycle StagesLinkLiverMeasurementMeasuresMediatingMesodermMetabolismMethodsMethylationModificationNon obeseNucleic Acid Regulatory SequencesNutrientObesityOocytesOutcomeParentsPathologicPathway interactionsPatternPeripheralPopulationPrevalenceProxyRecordsRegulationRisk AssessmentRoleSalivaSamplingSatiationScreening procedureSiteSomatic CellSpecific qualifier valueSpecificityTimeTissuesUmbilical Cord Bloodbisulfite sequencingcandidate identificationcandidate validationcell typecohortdeep sequencingdemethylationearly life exposureepigenetic regulationfetalgenetic variantgenome-widehistone modificationimprintinterestmaleobesity developmentobesity in childrenobesity riskpromoterprospectiveresponsescreeningsexsociodemographicssperm celltooltranscription factorwhole genome
项目摘要
PROJECT SUMMARY/ABSTRACT
The rapid increase in the prevalence of obesity in the last 30 years has led to the hypothesis that epigenetic mechanisms
mediate associations between environmental cues and obesity outcomes. Nevertheless, epigenetic regions that alter obesity
risk are still largely unknown. We presently lack a screening tool for comprehensive measurement of epigenetic modifications.
Such a screen in any disease or exposure of interest would be of great utility for a broad range of human health studies. The
interpretation of human epigenetic data generated using genome-scale approaches is hampered by three main obstacles.
Firstly, available data are largely based on methylation differences measured in DNA obtained cross-sectionally at different
ages throughout the life course, yet DNA methylation marks are known to vary by age. Secondly, although methylation is
known to vary by cell and tissue types, measurements are made in accessible peripheral cell types accessible from otherwise
healthy individuals, and do not always correlate with those of cell types that contribute to obesity. Thirdly, alteration to
epigenetic marks can be caused by obesity, and this temporal ambiguity between exposure and outcome complicates causal
inference. To overcome these obstacles, we will comprehensively identify regulatory DNA methylation for imprinted genes,
creating the first draft of the human “imprintome”. Epigenetically regulated imprinted genes are estimated to comprise 1-2%
(200-400 genes) of the human genome, and are critical in the development of the early embryo; however, only ~30 imprint
control regions (ICRs), regulating 70-80 genes, are known. Monoallelic expression of imprinted genes is regulated by parent-
of-origin specific DNA methylation at ICRs that is established prior to germ-layer specification and maintained in somatic
tissues throughout life. Therefore, methylation marks regulating the expression of these genes are functionally relevant, and
are conserved across cell types, among individuals, and throughout aging. These unique features of ICRs provide a means
to a comprehensive tool for multiplexed measurement of early acquired epigenetic modifications, and assess their link
between exposures and disease. Our overarching goal is to use genomewide approaches to systematically identify all ICRs
using a wide variety of samples, including multiple cell types from males and females from a wide age range. In this way,
identification can be restricted to only differentially methylated regions (DMRs) that are consistent across cell type, sex, and
age – the hallmark of ICRs. The ICR panel will then be evaluated in relationship to obesity, by identifying, in umbilical cord
blood at birth, ICR patterns predictive of obesity later in childhood. Identifying altered imprint regulation will provide markers
for prospective risk assessment, identify mechanisms contributing to obesity development, and inform future research into
environmental exposures affecting obesity. Once developed, this ICR screening assay would also then be used to identify
regions of early epigenetic perturbation associated with any disease or exposure, creating new opportunities for
understanding the fetal origins of these conditions.
项目总结/文摘
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)
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Cathrine Hoyo其他文献
Cathrine Hoyo的其他文献
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{{ truncateString('Cathrine Hoyo', 18)}}的其他基金
Prenatal stress and diet, and the fetal epigenome
产前压力和饮食,以及胎儿表观基因组
- 批准号:
10523353 - 财政年份:2022
- 资助金额:
$ 56.78万 - 项目类别:
Prenatal stress and diet, and the fetal epigenome
产前压力和饮食,以及胎儿表观基因组
- 批准号:
10665054 - 财政年份:2022
- 资助金额:
$ 56.78万 - 项目类别:
Novel imprint control regions (ICRs) responsive to environmental exposures
响应环境暴露的新型印记控制区域(ICR)
- 批准号:
10296917 - 财政年份:2021
- 资助金额:
$ 56.78万 - 项目类别:
Novel imprint control regions (ICRs) responsive to environmental exposures
响应环境暴露的新型印记控制区域(ICR)
- 批准号:
10655605 - 财政年份:2021
- 资助金额:
$ 56.78万 - 项目类别:
Characterizing the Human Imprint Regulatory Regions Associated with Childhood Obesity
表征与儿童肥胖相关的人类印记调节区域
- 批准号:
10442527 - 财政年份:2019
- 资助金额:
$ 56.78万 - 项目类别:
Characterizing the Human Imprint Regulatory Regions Associated with Childhood Obesity
表征与儿童肥胖相关的人类印记调节区域
- 批准号:
10180994 - 财政年份:2019
- 资助金额:
$ 56.78万 - 项目类别:
Characterizing the Human Imprint Regulatory Regions Associated with Childhood Obesity
表征与儿童肥胖相关的人类印记调节区域
- 批准号:
10011940 - 财政年份:2019
- 资助金额:
$ 56.78万 - 项目类别:
Follow-up and Maintenance of the Newborn Epigenetics STudy (NEST) Cohort
新生儿表观遗传学研究 (NEST) 队列的随访和维护
- 批准号:
10443683 - 财政年份:2018
- 资助金额:
$ 56.78万 - 项目类别:
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