Epigenetics, environmental exposure, and reproduction in the Collaborative Cross

协同杂交中的表观遗传学、环境暴露和繁殖

基本信息

批准号：
8281087
负责人：
David Lawrence Aylor
金额：
$ 8.79万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-06-01 至 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8281087
关键词：
Adverse effects Alleles Analysis of Variance Animal Model Biological Biological Assay Biological Models Chemical Exposure Chromosome Mapping Complex DNA Methylation Data Diethylstilbestrol Endocrine Disruptors Environment Environmental Exposure Epigenetic Process Equilibrium Estrogens Exposure to Gene Expression Gene Expression Regulation Genes Genetic Genetic Models Genetic Variation Genome Goals Health Human Inbred Mouse Inbred Strain Inbred Strains Mice Inbreeding Individual Knowledge Link Male Genital Organs Maps Measures Mentors Methods Modeling Molecular Molecular Biology Molecular Weight Mus Neonatal Pathway interactions Phenotype Physiological Physiology Play Population Population Control Population Heterogeneity Postdoctoral Fellow Predisposition Property Protocols documentation Quantitative Trait Loci Randomized Reproducibility Reproduction Reproductive Physiology Reproductive system Research Research Personnel Resources Role Series Sperm Count Procedure System Testing Testis Tissues Translating Variant bisulfite consumer product gene environment interaction insight mRNA Expression male public health relevance reproductive response trait xenoestrogen

项目摘要

DESCRIPTION (provided by applicant) The proposed research is a systems genetics approach to characterize the complex relationships between genetic variation, epigenetic regulation, gene expression, male reproductive physiology, and environmental exposure. To accomplish this goal, the investigators will leverage the power of diverse inbred mouse strains and the Collaborative Cross, a mouse reference population that has ideal properties for systems genetics. To identify gene-by-environment (GXE) interactions, the investigators will perturb the reproductive system with the powerful estrogen diethylstilbestrol (DES) and phenotype identical exposed and control populations. The investigators will measure DNA methylation, mRNA expression, and reproductive traits with the purpose of modeling genetic effects and GXE across three levels of genome function. This research will produce new biological knowledge of the genetic networks underlying the reproductive system, DES function at the molecular level, and genes underlying DES sensitivity. Public Health Relevance: Endocrine disrupting chemicals (EDCs) are used in many consumer products and most people are exposed to low levels of EDCs regularly. Mice have been used to show how EDC exposure can cause adverse effects on the reproductive system, but the mice used in these studies are usually genetically identical. Since the investigators know genetics are an important determinant of sensitivity to environmental exposures in humans, they propose to study EDC effects on reproduction in a newly available mouse resource that has a human-like amount of genetic variation.

描述（由申请人提供）拟议的研究是一种系统遗传学方法，旨在描述遗传变异、表观遗传调控、基因表达、男性生殖生理学和环境暴露之间的复杂关系。为了实现这一目标，研究人员将利用多种近交小鼠品系和协作杂交的力量，这是一种具有理想系统遗传学特性的小鼠参考群体。为了确定基因与环境（GXE）的相互作用，研究人员将使用强效雌激素己烯雌酚（DES）扰乱生殖系统，并使用表型相同的暴露人群和对照人群。研究人员将测量 DNA 甲基化、mRNA 表达和生殖特征，目的是对基因组功能三个层面的遗传效应和 GXE 进行建模。这项研究将产生有关生殖系统遗传网络、分子水平上的 DES 功能以及 DES 敏感性基因的新生物学知识。公共健康相关性：许多消费品中都使用内分泌干扰化学品 (EDC)，大多数人经常接触低含量的 EDC。小鼠已被用来展示 EDC 暴露如何对生殖系统造成不利影响，但这些研究中使用的小鼠通常在基因上是相同的。由于研究人员知道遗传学是人类对环境暴露敏感性的重要决定因素，因此他们建议研究 EDC 对新近可用的小鼠资源繁殖的影响，该小鼠资源具有与人类相似的遗传变异量。