Identification of fetal alcohol-affected children: Alterations in imprinted gene expression and methylation as biomarkers of neurobehavioral and growth impairment.

胎儿酒精影响儿童的鉴定：印记基因表达和甲基化的改变作为神经行为和生长障碍的生物标志物。

• 批准号: 10295640
• 负责人: ROBERT COLIN CARTER
• 金额: $ 6万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-23 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10295640
• 关键词: Address; Adverse effects; Affect; Alcohol consumption; Alcohol-Related Neurodevelopmental Disorder; Alcohols; Biological Markers; Blood; Cells; Child; Child Development; Color; Congenital Abnormality; Data; Diagnostic; Dysmorphology; Face; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Gene Expression; Genes; Growth; High Prevalence; Impairment; Infant; Intervention; Life; Longitudinal cohort study; Methylation; Neurodevelopmental Disorder; Neurodevelopmental Impairment; Parents; Placenta; Population; Pregnancy; Public Health; Reporting; Research; South Africa; Therapeutic Intervention; Tissues; Woman; binge drinking; cell type; early childhood; fetal; imprint; infancy; maternal alcohol use; neurobehavioral; public health relevance; single-cell RNA sequencing; tool; transcriptome sequencing

In the U.S. maternal alcohol use during pregnancy remains an important problem with approximately 10% of women consuming alcohol and 3% reporting binge drinking [1]. Fetal alcohol spectrum disorders (FASD) are the most common preventable cause of birth defects and neurodevelopmental disorders [2]. This problem is accentuated in heavily exposed populations like the Cape Coloured in South Africa, which has one of highest prevalence of FASD in the world [3]. Given the important consequences to child development of this prevalent exposure, it is imperative to identify early-life biomarkers that help identify children with FASD as early as possible so they can receive prompt targeted interventions [4]. This is the aim of the parent R01 study “Identification of fetal alcohol-affected children: Alterations in imprinted gene expression and methylation as biomarkers of neurobehavioral and growth impairment” (PI Dr. Carter). In Aim 1, the parent study will characterize imprinted gene expression biomarkers in blood and placental tissues from children prenatally exposed to alcohol and controls from the Cape Town longitudinal Cohort Study using RNA-seq. However, placental RNA-seq data to be generated from the parent study are composed of a mix of gene profiles from distinct cell- subtypes within a heterogenous tissue and to date there are no studies addressing this. The aim of the research in this supplement is to leverage recent placenta single-cell RNA-seq to construct a panel of cell-type specific gene makers to disentangle bulk placenta RNAs-seq data from the parent study and assess alcohol-related cell-type specific effects in these data.

在美国，怀孕期间的物物饮酒仍然是一个重要的问题 大约10％的妇女食用酒精和3％的报告暴饮暴食[1]。胎 酒精谱系（FASD）是最常见的先天缺陷原因 和神经发育障碍[2]。这个问题突然暴露了 像南非的斗篷般的种群，其患病率最高 世界上的FASD [3]。考虑到这种流行的儿童发展的重要后果 暴露，必须识别有助于识别FASD儿童的早期生物标志物 尽早可以收到及时的目标干预措施[4]。这是 父R01研究“鉴定受胎儿酒精影响儿童：印迹基因的改变 作为神经行为和生长障碍的生物标志物的表达和甲基化”（PI Dr. 卡特）。在AIM 1中，家长研究将表征印迹基因表达生物标志物 从产前暴露于酒精和对照的儿童的血液和斑点组织 开普敦使用RNA-Seq的纵向队列研究。但是，胎盘RNA-seq数据为 由家长研究产生的由来自不同细胞的基因谱的混合物组成 迄今为止，还没有解决此问题的研究。 该补充剂研究的目的是利用最近的plapeta单细胞RNA-Seq到 构建一组细胞类型的特定基因制造商，以解开散装量的plapeta rnas-seq数据 根据父母的研究并评估这些数据中与酒精相关的细胞类型的特异性效应。