DNA methylation differences between identical twins

描述（由申请人提供）： 大多数复杂的疾病都有遗传原因，但从家庭，特别是双胞胎的观察表明，其他因素几乎总是疾病的实际表现所必需的。一个这样的因素似乎是DNA单元的比例，有甲基基团连接到他们，或更准确地说，在重要的特定基因座的甲基化状态。已知甲基化水平在个体之间存在差异，并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，即使在同卵双胞胎中也是如此。其中一些变化可能是内部力量的结果，因此可能是随机出现的。然而，其他的则可能是由于环境暴露导致疾病或疾病出现之前的风险因素。这项研究旨在评估DNA甲基化状态与已知预测疾病发生的环境因素之间的联系。甲基化将使用更准确的焦磷酸测序方法进行测定，并在血细胞中进行研究，目前的许多理解都是基于血细胞，以及口腔鳞状上皮细胞，可能会更严重地暴露于高水平的环境因子。将比较有相关环境暴露史的双胞胎与相对未暴露的同卵双胞胎的甲基化水平。这些接触包括吸烟、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品和毒素。该计划还将根据居住地、职业暴露和饮食选择那些最不可能暴露于环境毒素的同卵双胞胎，以测量DNA甲基化的年龄特异性水平，以及这些水平与性别和双胞胎配对有关的程度。这些水平和指数的变化将进行比较，从性别，教育状况和母亲的教育状况（衡量儿童的社会阶层）的基础上选择对相同的结果。最后，将研究基于具有最少累积毒性暴露证据的同卵和同性异卵双胞胎的甲基化状态改变的遗传倾向的任何证据。

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.