Genetic and epigenetic interactions underlying FASD

FASD 背后的遗传和表观遗传相互作用

• 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
• 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

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. !

总结/摘要 乙醇是最常见的致畸剂，也是导致智力迟钝的主要原因。胎儿酒精暴露 可导致许多出生缺陷，最常见的是影响颅面骨骼和神经系统。 胎儿酒精谱系障碍描述了所有潜在的酒精诱导的出生缺陷， 据估计，每1000名新生儿中有10人患病。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的潜在因素，但我们对这些因素之间的相互作用几乎一无所知。的 斑马鱼胚胎对这些类型的分析特别有用。在目标1中，我们确定并表征 乙醇敏感基因模块和靶向它们的乙醇敏感miRNA。在目标2中，我们开发工具， 以确定miRNA活性如何改变细胞行为。由于基因功能的保守性， 斑马鱼和人类，我们的研究结果将提供关键的见解， FASD的遗传和表观遗传因素。 !