Project C: Epigenetic Effects of DDT/E and PBDEs on Puberty

表观遗传标记是在表型或基因表达没有变化的情况下可遗传的变化 DNA序列。DNA甲基化是最常见的表观遗传修饰类型，发挥着重要作用 在癌症、衰老、神经发育和生育方面。最近，血液DNA的全球甲基化的变化 与环境暴露有关，包括接触持久性有机污染物， 苯和空气污染。对儿童的DNA甲基化知之甚少，包括性别或性别的差异 年龄以及与健康终点或环境暴露的关联。 在这项提案中，我们将确定出生前和/或出生后接触滴滴涕/E和多溴二苯醚， 持续性内分泌干扰性毒物与胎儿整体和局部DNA甲基化有关 血液和9岁儿童的血液。我们还将确定DNA甲基化是否与 青春期开始的时间。最终，我们的目标是确定表观遗传修饰的特定遗传区域 可作为暴露或青春期发育异常的生物标志物。我们将使用丰富的集合 健康中心收集的生物样本、暴露信息和健康结果数据 对Salinas的母亲和儿童的评估(CHAMACOS)研究，601例纵向出生队列 妇女和儿童对DDT/E和多溴二苯醚有较高的暴露。在这个队列中，我们将：1) 通过Alu和Line-1重复序列的焦磷酸测序分析新生儿的全球DNA甲基化，以及 Infinium甲基化分析；2)确定出生时儿童整体甲基化的个体发育变化，1，5， 3)测定宫内血药浓度与9岁血药浓度的关系 DDT/E和PBDEs与全球甲基化；4)确定全球DNA甲基化是否与 青春期的开始和荷尔蒙的变化；以及5)检查全基因组位置特异性甲基化与 年龄、性别、接触DDT/E和多溴二苯醚与青春期开始。总样本量将为250名儿童 血液在出生时和9岁时可用。目标1、目标3、目标4和目标5将由随机选择的100个组成 发现集中的子项和复制集中的150个子项。AIM 2将包括50名儿童的子集 血液也在1岁、5岁和12岁。 表观遗传标记可能是环境暴露影响儿童健康的关键机制。 这项研究将提供一些关于儿童表观遗传学变化及其个体发育的第一批数据 与环境暴露和发育结果的关系。

Epigenetic markers are heritable changes in phenotype or gene expression in the absence of changes in DNA sequence. DNA methylation, the most common type of epigenetic modification, plays an important role in cancer, aging, neurodevelopment, and fertility. Recently, changes in global methylation in blood DNA have been associated with environmental exposures, including exposure to persistent organic pollutants, benzene, and air pollution. Little is known about DNA methylation in children, including variations with sex or age and associations with health endpoints or environmental exposures. In this proposal, we will determine whether pre- and/or postnatal exposures to DDT/E and PBDEs, persistent endocrine-disrupting toxicants, are related to global and site-specific DNA methylation in fetal blood and blood of 9-year-old children. We will also determine whether DNA methylation is related to the timing of puberty onset. Ultimately, we aim to identify specific genetic regions where epigenetic modifications can be used as biomarkers of exposure or abnormal pubertal development. We will use the rich collection of biological samples, exposure information, and health outcome data collected by the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a longitudinal birth cohort of 601 women and children with demonstrated high exposure to DDT/E and PBDEs. In this cohort, we will: 1) analyze global DNA methylation in newborn children by pyrosequencing of Alu and LINE-1 repeats, and Infinium Methylation assay; 2) determine ontogenetic changes in global methylation in children at birth, 1, 5, 9, and 12 years of age; 3) determine the relationship of in utero and 9-year-old blood concentrations of DDT/E and PBDEs with global methylation; 4) determine whether global DNA methylation is associated with onset of puberty and hormonal changes; and 5) examine genome-wide site-specific methylation in relation to age, sex, exposure to DDT/E and PBDEs and puberty onset. The total sample size will be 250 children with blood available at birth and 9 years of age. Aims 1, 3, 4 and 5 will be comprised of 100 randomly selected children in a Discovery set and 150 children in a Replication set. Aim 2 will include a subset of 50 children with blood also at 1, 5, and 12 years of age. Epigenetic markers may be a key mechanism by which environmental exposures affect children's health. This study will provide some of the first data on the ontogeny of epigenetic changes in children and their association with environmental exposures and developmental outcomes.