HUMAN MUTATIONAL SPECTROPHOTOMETRY--STUDIES IN THE ABERJONA

人类突变分光光度法——阿伯霍纳的研究

• 批准号: 3777174
• 负责人: WILLIAM G THILLY
• 金额: --
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3777174
• 关键词: B lymphocyte; biomarker; denaturing gradient gel electrophoresis; environmental toxicology; family genetics; gel electrophoresis; gene mutation; human genetic material tag; human population genetics; human subject; human tissue; industrial waste; method development; mitochondrial DNA; mutagens; nucleic acid sequence; polymerase chain reaction; ribosomal RNA; toxicant interaction; waste disposal; water pollution

The people of the Aberjona Basin live in a heavily contaminated watershed and apprehend real and present danger from exposure to chemicals emanating from two Superfund Sites and many other specific sites designated by the Massachusetts environmental authorities. We propose to initiate within this Program a long term study to discover the nature and, if possible, the causes of genetic change in the humans inhabiting the Aberjona Basin. We will strive in particular, to discover if any of the chemicals associated with the identified chemical dump sites are contributing to genetic change in the population. If we succeed our methods will be applicable to the study of any human population. Like our collaborators in the hydrologic engineering projects our proposal involves development of a general theory, creation of new analytical tools to test the theory and the use of these new tools in the context of the Aberjona Basin. Since every mutagen (studied in phage, bacteria, rodent and human cells) has produced a unique set of mutations with regard to kind and position our theory is that knowledge of such sets or mutational spectra in human tissue samples will yield invaluable information leading to the diagnosis of the primary cause(s) of these mutations. We specifically propose to define the kind and frequency of nuclear and mitochondrial mutations in blood samples of five multigenerational families residents in the Aberjona Valley. We will use this initial sample to test the statistical null hypotheses that (a) there are nor nonrandom features in the mutational spectra of ordinary citizens [Useful mutational spectral exist.] (b) There are no significant differences among the mutational spectra of unrelated citizens. [There is a primary cause of mutation in all people]. (c) There are no significant differences among the mutational spectra of members of the same family [There is a primary cause of mutation related to both genetic make up and environmental exposure]. (d) There are no significant differences between the mutational spectra for any individual and that produced by treatment of human B cells with suspect surface and ground water contaminants found in Aberjona water and sediments. Specifically - raw mixed sedimentary mutagens, chromium compounds, arsenicals, organic solvents and other such pure mutagenic compounds as may be identified in the work of Professor Hemond will have their mutational spectra determined. While the initial population study involves five multigenerational families living in the Aberjona, a significant amount of effort must still be invested in development and calibration of the general mensuration technology. Certain specific improvements in separation technology complementary to improvements in DNA amplification fidelity described in Project 0002 are made which are essential to our success.

阿伯乔纳盆地的人们生活在一个污染严重的流域 并了解接触化学品所产生的真实的和现实的危险 从两个超级基金网站和许多其他特定的网站指定的 马萨诸塞州环保部门。我们建议在 该计划是一项长期的研究，以发现性质，如果可能的话， 居住在阿伯乔纳盆地的人类基因变化的原因。 我们将特别努力，发现是否有任何化学物质 与已查明的化学品倾弃场有关的化学品， 人口的基因变化。 如果我们成功了我们的方法 适用于任何人群。 就像我们的合作者 在水文工程项目中，我们的建议涉及开发 一般理论，创造新的分析工具来测试理论 以及这些新工具在阿贝乔纳盆地的应用。 因为每一种诱变剂（在噬菌体、细菌、啮齿动物和人类细胞中研究） 在种类和位置上产生了一系列独特的突变 我们的理论是，人类基因组或突变谱的知识 组织样本将提供宝贵的信息，导致诊断 这些突变的主要原因。 我们特别建议界定核武器的种类和频率， 五个多代同堂的人的血液样本中的线粒体突变 阿伯乔纳山谷的居民。 我们将使用这个首字母 样本来检验统计零假设，即（a） 普通公民突变谱中的非随机特征[有用 突变谱存在。] (b)之间没有显著差异 无关公民的突变谱 [有一个主要原因 所有的人都有变异。(c)之间没有显著差异 同一家族成员的突变谱[有一个主要的 突变的原因与遗传和环境有关 暴露]。(d)在突变型之间没有显著差异， 任何个体的光谱和处理人B细胞产生的光谱 在阿伯乔纳水中发现了可疑的地表水和地下水污染物 和沉积物。 特别是-原始混合沉积诱变剂，铬 化合物、砷剂、有机溶剂和其他此类纯诱变剂 在赫蒙德教授的工作中可能发现的化合物将具有 它们的突变谱已确定。 虽然最初的人口研究涉及五个多代 生活在阿伯乔纳的家庭，大量的努力仍然必须 投资开发和校准通用测定 技术. 分离技术的某些具体改进 这是对DNA扩增保真度的改进的补充， 第0002章这是我们成功的关键