PCB Epigenomic Brain & Behavior Lasting Effects Study (PEBBLES)
PCB表观基因组大脑
基本信息
- 批准号:10183250
- 负责人:
- 金额:$ 47.3万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-06-01 至 2023-05-31
- 项目状态:已结题
- 来源:
- 关键词:ATAC-seqAdolescenceAdultAffectAgeAttentionAttention deficit hyperactivity disorderBehaviorBehavioralBioinformaticsBiological MarkersBirthBlood specimenBrainCellsChildChromatinCognitiveCohort StudiesComplementComplexConfounding Factors (Epidemiology)DNADNA MethylationDNA analysisDNA methylation profilingDataData AnalysesDevelopmentDiagnosisDisease modelDoseEmbryoEnhancersEnvironmentEnvironmental ExposureEnvironmental HealthEnvironmental Risk FactorEpigenetic ProcessEventExperimental ModelsExposure toFamily history ofFemaleFreezingGeneral PopulationGenesGeneticGenetic MarkersGenetic ModelsGenetic RiskGenetic ScreeningGenomeGenotypeGestational AgeGoalsHeterogeneityHumanLanguage DelaysLearningMapsMarbleMeasurementMeasuresMethylationMolecularMolecular GeneticsMolecular ProfilingMonitorMothersMusNeurodevelopmental DisorderNeurologicOutcomeOutcome MeasurePathway interactionsPerinatal ExposurePhenotypePlacentaPlasmaPolychlorinated BiphenylsPopulationPopulations at RiskPregnancyRiskRisk MarkerRodentRodent ModelSample SizeSamplingScientistSerumSeveritiesSiblingsSourceSpecificityStatistical Data InterpretationTechnologyTestingTimeTissuesUnited StatesUrineautism spectrum disorderbasebehavioral outcomebisulfite sequencingblastocystbrain behaviorbrain tissuecapsulecell free fetal DNAcell typecohortepigenetic markerepigenomeepigenomicsfetalgenome wide methylationgenomic datahealth planhigh riskimproved outcomein uteromalemethylation biomarkermethylation patternmethylomemouse modelneurodevelopmentneurotoxicpersistent organic pollutantsphenotypic datapredictive markerpregnantprenatal exposureprospectiverecruittranscriptometranscriptome sequencingtrophoblastwhole genome
项目摘要
Placental tissue is normally discarded at birth, but is essentially a molecular time capsule for
gene by environmental interactions and dysregulated molecular and cellular pathways that
can be revealed at the level of the epigenome. Identifying epigenetic biomarkers at birth that
reflect in utero exposures or predict adverse neurodevelopmental outcomes is an important
goal that has been limited by prior technologies or lack of relevant tissue availability. Our
team of currently collaborating interdisciplinary scientists within the Children’s Center for
Environmental Health plans to use existing placental samples from a prospective high-risk
cohort study (MARBLES) to identify epigenetic biomarkers at birth for in utero exposure to
polychlorinated biphenyls (PCB) and neurodevelopmental outcomes by age three. Using
unbiased whole genome bisulfite sequencing (WGBS), we have previously demonstrated
that placental tissues retain the distinctive DNA methylation patterns of the preimplantation
embryo and so can capture the molecular state in very early development, a feature that is
conserved across mammalian species, including mouse. The new hypothesis to be tested in
this proposal is that perinatal exposures to PCB adversely impact neurodevelopment and
leave a lasting molecular signature over genes relevant to neurodevelopment that can be
detected in placenta. The proposed PCB Epigenomic Brain & Behavior Lasting Effects
Study (PEBBLES) will combine the analysis of human placental samples from the high-risk
MARBLES cohort with the analysis of placenta and brain tissues and sorted cell types
derived from a mouse model of perinatal exposure to the same mixture of PCB congeners
detected in MARBLES mothers. This study will leverage existing neurological and
behavioral analyses and samples to examine the relationship between PCB-induced
perturbations of DNA methylation marks with adverse neurotoxic outcomes. Epigenomic
analyses of placenta and brain as well as sorted cellular subtypes from each of these
tissues will include WGBS for methylome, RNA-seq for transcriptome, and ATAC-seq for
chromatin accessibility. Bioinformatic and statistical analyses will integrate the genomic data
sets with behavioral and molecular outcome measures and determine whether similar
epigenetic marks are observed in placenta that could be used to predict long-lasting adverse
brain and behavioral outcomes in humans.
!
胎盘组织通常在出生时被丢弃,但本质上是一个分子时间胶囊,
基因与环境的相互作用和失调的分子和细胞途径,
可以在表观基因组的水平上揭示出来。在出生时识别表观遗传生物标志物,
反映子宫内暴露或预测不良神经发育结果是一个重要的
这一目标受到现有技术或缺乏相关组织可用性的限制。我们
目前在儿童中心合作的跨学科科学家团队,
环境卫生计划使用现有的胎盘样本,从一个前瞻性的高风险
队列研究(MARBLES),以确定出生时子宫内暴露于
多氯联苯(PCB)和神经发育的结果。使用
无偏全基因组亚硫酸氢盐测序(WGBS),我们以前已经证明
胎盘组织保留了着床前的独特DNA甲基化模式,
胚胎,因此可以捕捉分子状态在非常早期的发展,这是一个特点,
在哺乳动物物种中是保守的,包括小鼠。新的假设将在
这一建议是,围产期暴露于多氯联苯对神经发育产生不利影响,
在与神经发育相关的基因上留下持久的分子标记,
在胎盘中检测到。拟议的PCB表观基因组大脑和行为持久效应
研究(PEBBLES)将结合联合收割机对来自高危人群的人胎盘样本的分析,
MARBLES队列分析胎盘和脑组织以及分选的细胞类型
来自围产期接触相同多氯联苯同系物混合物的小鼠模型
在大理石母亲身上检测到。这项研究将利用现有的神经和
行为分析和样本,以检查多氯联苯引起的
DNA甲基化标记的扰动与不良神经毒性结果。表观
胎盘和大脑的分析以及来自这些中的每一个的分类的细胞亚型
组织将包括甲基化组的WGBS、转录组的RNA-seq和
染色质可及性生物信息学和统计分析将整合基因组数据
与行为和分子结果的措施,并确定是否类似
在胎盘中观察到表观遗传标记,可用于预测长期不良反应,
大脑和行为的结果。
!
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 }}
Janine M LaSalle其他文献
Janine M LaSalle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('Janine M LaSalle', 18)}}的其他基金
Placental identified NHIP regulating neuronal oxidative stress in autism
胎盘发现 NHIP 调节自闭症神经元氧化应激
- 批准号:
10717990 - 财政年份:2023
- 资助金额:
$ 47.3万 - 项目类别:
Imprinted snoRNA loci and circadian entrainment
印记 snoRNA 位点和昼夜节律夹带
- 批准号:
10535437 - 财政年份:2019
- 资助金额:
$ 47.3万 - 项目类别:
Imprinted snoRNA loci and circadian entrainment
印记 snoRNA 位点和昼夜节律夹带
- 批准号:
10319981 - 财政年份:2019
- 资助金额:
$ 47.3万 - 项目类别:
PCB Epigenomic Brain & Behavior Lasting Effects Study (PEBBLES)
PCB表观基因组脑
- 批准号:
10416017 - 财政年份:2018
- 资助金额:
$ 47.3万 - 项目类别:
Epigenomic Brain & Behavior Lasting Effects Study (PEBBLES) Admin Supplement
表观基因组脑
- 批准号:
9916517 - 财政年份:2018
- 资助金额:
$ 47.3万 - 项目类别:
Methylomic and genomic impacts of organic pollutants in Dup15q syndrome
有机污染物对 Dup15q 综合征的甲基组学和基因组影响
- 批准号:
8914907 - 财政年份:2012
- 资助金额:
$ 47.3万 - 项目类别:
Methylomic and genomic impacts of organic pollutants in Dup15q syndrome
有机污染物对 Dup15q 综合征的甲基组学和基因组影响
- 批准号:
8487405 - 财政年份:2012
- 资助金额:
$ 47.3万 - 项目类别:
相似海外基金
Cognitive and non-cognitive abilities and career development during adolescence and adult development: from the perspective of genetic and environmental structure
青春期和成人发展期间的认知和非认知能力与职业发展:从遗传和环境结构的角度
- 批准号:
23K02900 - 财政年份:2023
- 资助金额:
$ 47.3万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
ADOLESCENCE: A SENSITIVE PERIOD FOR SHAPING THE ADULT SOCIAL BRAIN
青春期:塑造成人社交大脑的敏感时期
- 批准号:
RGPIN-2022-05266 - 财政年份:2022
- 资助金额:
$ 47.3万 - 项目类别:
Discovery Grants Program - Individual
Joint contributions of affiliative social contact, stress in adolescence and oxytocin to fear behaviour in adult rats
亲和性社会接触、青春期压力和催产素对成年大鼠恐惧行为的共同作用
- 批准号:
RGPIN-2019-04790 - 财政年份:2022
- 资助金额:
$ 47.3万 - 项目类别:
Discovery Grants Program - Individual
Joint contributions of affiliative social contact, stress in adolescence and oxytocin to fear behaviour in adult rats
亲和性社会接触、青春期压力和催产素对成年大鼠恐惧行为的共同作用
- 批准号:
RGPIN-2019-04790 - 财政年份:2021
- 资助金额:
$ 47.3万 - 项目类别:
Discovery Grants Program - Individual
ADOLESCENCE: A SENSITIVE PERIOD FOR SHAPING THE ADULT SOCIAL BRAIN
青春期:塑造成人社交大脑的敏感时期
- 批准号:
RGPIN-2016-03714 - 财政年份:2021
- 资助金额:
$ 47.3万 - 项目类别:
Discovery Grants Program - Individual
Impact on adult mouse brain of oral THC and CBD consumption during adolescence
青春期口服 THC 和 CBD 对成年小鼠大脑的影响
- 批准号:
10206087 - 财政年份:2020
- 资助金额:
$ 47.3万 - 项目类别:
Joint contributions of affiliative social contact, stress in adolescence and oxytocin to fear behaviour in adult rats
亲和性社会接触、青春期压力和催产素对成年大鼠恐惧行为的共同作用
- 批准号:
RGPIN-2019-04790 - 财政年份:2020
- 资助金额:
$ 47.3万 - 项目类别:
Discovery Grants Program - Individual
Investigating the Social Determinant and Developmental Risk Patterns in Childhood and Adolescence Associated with Adult Asthma and Diabetes Onset
调查儿童期和青少年期与成人哮喘和糖尿病发病相关的社会决定因素和发育风险模式
- 批准号:
450250 - 财政年份:2020
- 资助金额:
$ 47.3万 - 项目类别:
Studentship Programs
ADOLESCENCE: A SENSITIVE PERIOD FOR SHAPING THE ADULT SOCIAL BRAIN
青春期:塑造成人社交大脑的敏感时期
- 批准号:
RGPIN-2016-03714 - 财政年份:2020
- 资助金额:
$ 47.3万 - 项目类别:
Discovery Grants Program - Individual
Impact on adult mouse brain of oral THC and CBD consumption during adolescence
青春期口服 THC 和 CBD 对成年小鼠大脑的影响
- 批准号:
10039866 - 财政年份:2020
- 资助金额:
$ 47.3万 - 项目类别: