A biocultural investigation of epigenetics, gene expression and the intergenerational effects of stress in mothers and neonates

表观遗传学、基因表达以及母亲和新生儿压力的代际影响的生物文化研究

基本信息

批准号：
1719866
负责人：
Connie Mulligan
金额：
$ 49.94万
依托单位：
University of Florida
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-06-15 至 2022-05-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1719866&HistoricalAwards=false
关键词：
biocultural investigation epigenetics gene expression

项目摘要

This project will investigate relationships among maternal stress, epigenetic markers, and infant outcomes in a sample of mother-infant pairs in which the mothers experienced extreme stress during pregnancy. The goal of the research is to better understand how epigenetic mechanisms may link stress in one generation and changes in gene expression and later-life outcomes in the next generation. The idea that stress, including psychosocial stress, may be related physiologically to changes in an offspring's outcomes later in life is central to many anthropological models of growth, development, adaptation and plasticity. The research findings also will be potentially informative for understanding the increasing prevalence of stress-related disorders in the United States. This project will support ongoing international research collaborations and integrative graduate training in biological, cultural, and medical anthropology for students from groups underrepresented in STEM fields. One of the most stressful environments today is found in the Democratic Republic of Congo (DRC) where war and post-war conflict has ravaged the country for over 20 years. This project will investigate the role of DNA methylation and gene expression in translating experiences of violence and stress in a sample of mothers into altered well-being outcomes for those mothers and their offspring. The project will therefore advance our understanding of human phenotypic plasticity, a central theme in anthropological, biocultural research. The proposed biocultural approach integrates sophisticated ethnographic, epigenomic, transcriptomic, and hormonal data; a wealth of biological samples, maternal stress exposures and neonate/maternal outcomes have already been collected for 100 mother-infant pairs. The biological samples will be assayed for DNA methylation (Illumina MethylationEPIC BeadChip), gene expression (Agilent SurePrint G3 Human Gene Expression array), and cortisol-based stress measures (ELISA and LC-MS). Associations among maternal stress, DNA methylation, gene expression and neonate/maternal outcomes will be tested using multiple regression analyses, to better understand the biological and molecular mechanisms that underlie adaptive responses to stress. The project will focus on genes involved in the stress process, e.g., HPA axis genes, as well as the entire genome to test for genome-wide effects of stress.

该项目将调查母亲压力，表观遗传标记和婴儿结局之间的关系，其中母亲在怀孕期间母亲会遇到极大的压力。该研究的目的是更好地了解表观遗传机制如何将一代人的压力与基因表达的变化和下一代的后期寿命联系起来。压力（包括社会心理压力）的想法可能与后代后代结果的变化在生理上与许多人类学模型的增长，发展，适应和可塑性有关。研究结果也将有可能提供信息，以了解美国与压力相关的疾病的普遍性日益增长。该项目将为正在进行的国际研究合作和综合研究生培训，从事生物，文化和医学人类学的综合研究生培训，这些培训是来自STEM领域中代表性不足的学生的生物，文化和医学人类学。当今最受压力的环境之一是在刚果民主共和国（DRC）中发现的，战争和战后冲突已经破坏了该国已有20多年了。该项目将研究DNA甲基化和基因表达在将母亲样本中的暴力和压力经历转化为那些母亲及其后代的福祉结果中的作用。因此，该项目将提高我们对人类表型可塑性的理解，这是人类学，生物文化研究中的核心主题。提出的生物文化方法整合了复杂的人种学，表观基因组，转录组和荷尔蒙数据。已经收集了大量的生物样品，孕产妇的压力暴露和新生儿/孕产妇结局，以收集100对母亲。该生物样品将分析用于DNA甲基化（Illumina甲基化珠珠），基因表达（Agilent SurePrint G3人基因表达阵列）和基于皮质醇的胁迫度量（ELISA和LC-MS）。孕产妇应力，DNA甲基化，基因表达和新生儿/产妇结局之间的关联将使用多元回归分析进行测试，以更好地了解构成对压力的适应性反应的生物学和分子机制。该项目将集中于应力过程中涉及的基因，例如HPA轴基因以及整个基因组，以测试应激的全基因组效应。