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：
7645040
负责人：
THOMAS McCulloch MACK
金额：
$ 52.97万
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 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7645040
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 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 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，但是家庭，尤其是双胞胎的观察结果表明，其他因素几乎始终是疾病实际出现所必需的。这样的因素似乎是在其上附着甲基的DNA单元的比例，或更准确地是在重要特定基因座的甲基化状态。已知甲基化水平在个体之间有所不同，并且与几种慢性疾病有关。该水平已被证明随着年龄的增长而变化，即使在相同的双胞胎对成员之内。其中一些变化可能是内源力的结果，因此很可能是随机出现的。但是，其他人可能是导致疾病或外观之前的危险因素的环境暴露的结果。这项研究旨在评估DNA甲基化状态与已知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测定甲基化，并在血细胞中进行研究，当前许多理解都基于的大部分理解和鳞状上皮细胞从口腔中进行了研究，可能会更严重地暴露于高水平的环境药物中。在相对未暴露的相同二线中，将比较双胞胎的甲基化水平。此类暴露的清单包括吸烟，饮酒，肥胖症，已知含有叶酸的食物和已知的含有致癌物的食物，以及对各种环境化学物质和毒素的职业和住宅暴露。该计划还要选择基于居住，职业暴露和饮食的那些最不可能暴露于环境毒素的同卵双胞胎，以测量特定年龄的DNA甲基化水平以及那些程度的程度与性别和双胞胎对有关的水平各不相同。这些差异的水平和指标将与根据性别，教育地位和孕产妇教育地位（对儿童社会阶层的衡量）选择的对成对的相同发现进行比较。最后，将研究任何证据表明，基于相同的性爱兄弟双胞胎，具有遗传甲基化状态的倾向，将研究最少证据表明累积毒性暴露的证据。