权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Examining tissue-specific DNA methylation after prenatal exposure to arsenic among infants with spina bifida

脊柱裂婴儿产前暴露于砷后检查组织特异性 DNA 甲基化

基本信息

批准号：
9978432
负责人：
Maitreyi Mazumdar
金额：
$ 28.04万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-16 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9978432
关键词：
Address Affect Anencephaly and spina bifida X linked Arsenic Bangladesh Basic Science Birth Rate Blood Brain Candidate Disease Gene Cells Chronic Chronic lung disease Clinical Clinical Sciences Collaborations Congenital Abnormality DNA DNA Methylation DNA Sequence Data Development Diabetes Mellitus Disease Embryo Environmental Exposure Epigenetic Process Exposure to Folic Acid Future Gene Expression Genes Genetic Predisposition to Disease Genetic Transcription Goals Health Human Individual Infant Intake Intervention Investigation Kidney Cortex Necrosis Live Birth Low Birth Weight Infant Malignant neoplasm of lung Mediating Meningomyelocele Methods Mothers Nervous system structure Neural Tube Closure Neural Tube Defects Neural Tube Development Neural tube Neuroepithelial Tissue Nucleotides Nutritional Operative Surgical Procedures Outcome Pattern Peripheral Nervous System Diseases Phenotype Pilot Projects Population Pregnancy Premature Birth Prevalence Preventive Intervention Resolution Risk Sampling Series Severities Spinal Cord Spinal Dysraphism Swab Testing Tissues Toxic effect bisulfite sequencing contaminated drinking water design drinking water epidemiology study epigenome epigenome-wide association studies high reward high risk innovation methylation pattern nervous system disorder neural plate neurotoxicity nutrition prenatal prenatal exposure prevent protective effect skin lesion transcriptome sequencing whole genome

项目摘要

PROJECT SUMMARY/ABSTRACT Arsenic contamination in drinking water continues to be a major health threat worldwide. An emerging hypothesis is that arsenic acts via the epigenome, the multitude of compounds that affect DNA transcription of specific genes but do not alter DNA sequence. Better understanding of this important potential mechanism of arsenic toxicity is essential to design strategies to prevent and treat arsenic-related diseases. Neural tube defects, including spina bifida and anencephaly, are common and severe birth defects that occur when the embryonic precursors to the brain and spinal cord do not properly develop. Neural tube defects are increasingly considered to be among the sequelae of arsenic exposure. In this R21 application, we test the hypothesis that arsenic's effects on the developing nervous system are mediated through the epigenome. We propose to use readily accessible nervous system tissue that is exposed as a result of the birth defect to test our hypotheses. In this application, we establish a new basic science-clinical science collaboration to determine DNA methylation patterns from various tissues from a human population of infants with myelomeningocele, a common and severe form of neural tube defect. Our clinical group is currently conducting an epidemiological study in Bangladesh to determine whether maternal arsenic exposure through contaminated drinking water increases the risk of myelomeningocele. We have recently started collecting discarded tissue from surgical closure of the myelomeningocele, and these samples provide a unique opportunity to investigate tissue- specific epigenetic patterns. We propose a series of pilot studies that will whole genome bisulfite sequencing (WGBS), a new and innovative method that enables investigation of DNA methylation at a single-nucleotide resolution, to examine DNA methylation in candidate genes known to be important in neural tube defects in the blood and nervous system tissue of affected infants. These high risk, high reward studies will identify genes that are differentially methylated in relation to arsenic exposure and phenotype, as well as test the hypothesis that neuroepithelial tissue provides a unique window into the study of human neural tube defects. These studies will also provide important preliminary data for future collaborative projects such as epigenome-wide association studies (EWAS). Such studies are highly likely to provide new targets for preventive interventions.

项目总结/文摘