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，母亲在怀孕期间饮酒仍然是一个重要的问题， 大约10%的女性饮酒，3%的女性报告酗酒[1]。胎儿 酒精谱系障碍（FASD）是出生缺陷最常见的可预防原因 和神经发育障碍[2]。这一问题在严重暴露于 像南非的开普有色人种， 世界上的FASD [3]。考虑到这种流行病对儿童发展的重要影响， 因此，必须确定早期生命生物标志物，以帮助识别FASD儿童 尽早采取有针对性的干预措施[4]。这是我们的目标。 母体R 01研究“胎儿酒精影响儿童的识别：印记基因的改变 表达和甲基化作为神经行为和生长障碍的生物标志物”（PI Dr. Carter）。在目标1中，母研究将表征以下中的印迹基因表达生物标志物： 产前暴露于酒精的儿童的血液和胎盘组织， 使用RNA-seq的开普敦纵向队列研究。然而，胎盘RNA-seq数据将被 从母体研究中产生的基因图谱由来自不同细胞的基因图谱组成， 在异质组织内的亚型，并且迄今为止没有研究解决这个问题。 本补充研究的目的是利用最近的胎盘单细胞RNA-seq， 构建一组细胞类型特异性基因标记以解开大量胎盘RNAs-seq数据 并评估这些数据中酒精相关的细胞类型特异性效应。