DNA methylation differences between identical twins

同卵双胞胎之间的 DNA 甲基化差异

基本信息

批准号：
7288741
负责人：
THOMAS McCulloch MACK
金额：
$ 68.46万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-21 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7288741
关键词：
Aftercare Age Air Pollution Alcohol consumption Alcohols Appearance Biological Assay Birth Birth Order Blood Blood Cells Breast Carcinogens Categories Chemicals Childhood Chromosomes Chronic Disease Colon Complex Condition DNA DNA Methylation DNA Sequence Diet Disease Dizygotic Twins Dust Education Educational Status Environment Environmental Exposure Environmental Risk Factor Epigenetic Process Epithelial Cells Ethnic Origin European Evaluation Exposure to Family Folate Folic Acid Food Food Preferences Gender Genetic Genome Genus Cola Individual Infection Latino Link Lung Lymphocyte Malignant Neoplasms Marital Status Maternal Age Maternal Educational Status Measures Meat Medical Medical History Methods Methylation Monozygotic twins Obesity Occupational Occupational Exposure Oral cavity Pattern Peptic Ulcer Pesticides Prostate Pylorus Radiation therapy Recording of previous events Resources Risk Factors Sampling Severity of illness Smoke Smoking Social Class Solvents Specific qualifier value Squamous Cell Staging Swab Toxic Environmental Substances Toxicant exposure Toxin Twin Multiple Birth Variant base chemotherapy environmental agent environmental chemical exhaust food consumption indexing member methyl group preference residence sex

项目摘要

DESCRIPTION (provided by applicant): Most complex diseases have genetic causes, but observations from families and especially from twins indicate that other factors are almost always necessary for the actual appearance of disease. One such factor appears to be the proportion of DNA units that have methyl groups attached to them, or more accurately the methylation status at important specific loci. The level of methylation is known to vary between individuals and has been linked to several chronic diseases. The level has been shown to change with increasing age, even within the members of identical twin pairs. Some of these changes are probably the result of endogenous forces and therefore are likely to have appeared at random. Others, however, are likely to be the result of the environmental exposures that cause disease or the risk factors that precede its appearance. This study seeks to evaluate the linkage between the DNA methylation status and environmental factors known to predict disease occurrence. Methylation will be assayed using the more accurate pyrosequencing method, and studied both in blood cells, upon which much of the current understanding is based, and squamous epithelial cells from the mouth, likely to be more heavily exposed to high levels of environmental agents. The level of methylation will be compared in twins who give a history of pertinent environmental exposure, to that in their relatively unexposed identical co-twins. The list of such exposures includes smoking, alcohol usage, obesity, consumption of foods known to contain folic acid and food known to contain carcinogens, and occupational and residential exposure to various environmental chemicals and toxins. The plan is to also select those sets of identical twins least likely to have been exposed to environmental toxins, based on residence, occupational exposure, and diet, in order to measure the age-specific levels of DNA methylation, and the degree to which those levels vary in relation to sex and twin pair. These levels and indices of variation will be compared to the same findings from pairs selected on the basis of sex, educational status, and maternal educational status (a measure of childhood social class). Finally, any evidence of a heritable propensity to change methylation status, based on identical and like sex fraternal twins having the least evidence of cumulative toxic exposure, will be investigated.

描述（由申请人提供）：大多数复杂的疾病都有遗传原因，但来自家庭，尤其是双胞胎的观察表明，其他因素几乎总是疾病实际出现所必需的。其中一个因素似乎是带有甲基的 DNA 单位的比例，或更准确地说是重要特定位点的甲基化状态。已知甲基化水平因人而异，并且与多种慢性疾病有关。研究表明，即使在同卵双胞胎中，这一水平也会随着年龄的增长而变化。其中一些变化可能是内生力的结果，因此很可能是随机出现的。然而，其他的可能是由于暴露于导致疾病的环境或疾病出现之前的危险因素造成的。本研究旨在评估 DNA 甲基化状态与已知可预测疾病发生的环境因素之间的联系。将使用更准确的焦磷酸测序方法对甲基化进行测定，并在血细胞（目前的大部分理解都基于血细胞）和口腔鳞状上皮细胞（可能更严重地暴露于高水平的环境因子）中进行研究。将比较有相关环境暴露史的双胞胎和相对未暴露的同卵双胞胎的甲基化水平。此类暴露的清单包括吸烟、饮酒、肥胖、食用已知含有叶酸的食物和已知含有致癌物质的食物，以及职业和住宅接触各种环境化学物质和毒素。该计划还根据居住地、职业暴露和饮食，选择那些最不可能接触环境毒素的同卵双胞胎，以测量特定年龄的 DNA 甲基化水平，以及这些双胞胎的 DNA 甲基化水平。水平因性别和双胞胎而异。这些水平和变异指数将与根据性别、教育状况和母亲教育状况（儿童社会阶层的衡量标准）选择的配对的相同结果进行比较。最后，将根据累积毒性暴露证据最少的同卵双胞胎和同性异卵双胞胎，对任何改变甲基化状态的遗传倾向的证据进行调查。