Genetic and epigenetic interactions underlying FASD

FASD 背后的遗传和表观遗传相互作用

基本信息

批准号：
9196218
负责人：
JOHANN K EBERHART
金额：
$ 21.71万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-15 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9196218
关键词：
Alcohols Anabolism Binding Sites Biological Assay Birth Cells Collaborations Congenital Abnormality Data Defect DsRed Embryo Epigenetic Process Ethanol Face Fetal Alcohol Exposure Fetal Alcohol Spectrum Disorder Fluorescence Genes Genetic Genetic Counseling Genetic Predisposition to Disease Genetic Screening Heterozygote Human Learning Measures Mediating Mental Retardation Messenger RNA Methods MicroRNAs Nervous system structure Pathway Analysis Pathway interactions Phenotype Predisposition Prevalence Reporter Repression Risk Factors Skeleton Staging Susceptibility Gene System Teratogens Testing Time Transcript Transcription Coactivator Transgenic Organisms Translating Untranslated Regions Weight Zebrafish abstracting alcohol effect alcohol exposure alcohol sensitivity attenuation austin base cell behavior cell motility convergent extension craniofacial dosage gastrulation gene function human disease in vivo insight member mutant planar cell polarity promoter sensor tool

项目摘要

Summary/Abstract Ethanol is the most common teratogen and the leading cause of mental retardation. Fetal alcohol exposure can cause numerous birth defects, most commonly effecting the craniofacial skeleton and nervous system. Fetal Alcohol Spectrum Disorder describes the full range of potential ethanol-induced birth defects and has been estimated to have a prevalence of 10 in 1000 births. The timing and concentration of fetal alcohol exposure are important determinants of FASD phenotypes. There also appears to be genetic and epigenetic factors underlying FASD, yet we know almost nothing about the interaction between these factors. The zebrafish embryo is particularly useful for these types of analyses. In Aim 1, we identify and characterize ethanol-sensitive gene modules and the ethanol-sensitive miRNAs that target them. In Aim 2, we develop tools to determine how miRNA activity alters cell behaviors. Because of the conservation of gene function between zebrafish and humans, the results from our studies will provide key insights into the interaction between genetic and epigenetic factors underlying FASD. !

摘要/摘要乙醇是最常见的致病原，也是智力低下的主要原因。胎儿酒精暴露可能导致许多先天缺陷，最常见地影响颅面骨骼和神经系统。胎儿酒精谱系障碍描述了潜在乙醇引起的先天缺陷的全部范围，并且具有据估计，1000个出生的患病率为10。胎儿酒精的时间和浓度暴露是FASD表型的重要决定因素。似乎也有遗传和表观遗传 FASD的基础因素，但我们几乎对这些因素之间的相互作用一无所知。这斑马鱼胚胎对于这类分析特别有用。在AIM 1中，我们确定和表征乙醇敏感的基因模块和靶向它们的乙醇敏感的miRNA。在AIM 2中，我们开发工具确定miRNA活性如何改变细胞行为。由于基因功能之间的保存斑马鱼和人类，我们的研究结果将为您提供关键的见解 FASD的遗传和表观遗传因素。呢