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，孕妇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)是导致出生缺陷的最常见的可预防原因 和神经发育障碍[2]。这个问题在被大量曝光的情况下被突出了 像开普省这样的有色人种在南非是发病率最高的国家之一 世界上的FASD[3]。鉴于这种流行的疾病对儿童发展的重要后果 暴露后，必须确定有助于确定患有FASD儿童的早期生物标记物 越早越好，这样他们就能得到及时、有针对性的干预[4]。这就是 父母R01研究《胎儿酒精影响儿童的鉴定：印记基因的改变》 表达和甲基化是神经行为和生长障碍的生物标记物“(PiDr。 卡特)。在目标1中，父母的研究将表征印记基因表达的生物标记物 产前接触酒精的儿童和对照儿童的血液和胎盘组织 开普敦纵向队列研究使用RNA-SEQ。然而，胎盘RNA-seq数据有待于 从父母的研究中产生的基因图谱由不同细胞的基因图谱组成- 异种组织中的亚型，到目前为止还没有研究解决这一问题。 本附录的研究目的是利用最近的胎盘单细胞rna-seq来 构建一组细胞类型特异性基因标记物以解开大量胎盘rna-seq数据 从父母那里研究并评估这些数据中与酒精相关的细胞类型的特定影响。