Pyrosequencer

描述（由申请人提供）：近年来，环境医学系加强了对遗传多态性与各种癌症易感性之间关系的评估工作，并成功地在该系流行病学和分子毒理学/致癌学项目的研究人员之间提出了NIH合作资助申请。此外，该部门的几名成员在评估致癌模型中CpG岛DNA甲基化的表观遗传效应方面有着长期的NIH资助记录。此外，环境医学成功获得了超级基金基础研究项目中心拨款，题为“超级基金化学品的遗传/表观遗传易感性”，这反映了在这些领域的努力。由部门调查人员资助的其他NIH资助项目涉及开发以单核苷酸多态性为标记的连锁图谱，以识别与毒物诱发疾病相关的新基因。有了这个申请，我们建议获得一个焦氧测序仪TM，安置在环境医学长期NIEHS中心的共享分子设施核心中。该仪器用于提高由本部门成员资助的多个NIH基因分型研究的通量和准确性。通过增加样本和基因座数量，这些研究将在评估遗传多态性对疾病易感性的影响方面更加敏感。同样，研究甲基化状态与致癌关系的研究人员将能够扩展他们的分析，包括短段DNA内的多个CpG岛，现在将能够定量估计单个岛上高甲基化核苷酸的百分比。需要该仪器的几个研究小组获得的NIH拨款支持表明他们正在进行高质量的科学研究；随着Pyrosequencer的收购，他们将能够进行更广泛和详细的调查，这将使他们能够在他们的研究领域保持领先地位。

DESCRIPTION (provided by applicant): Efforts to evaluate the relationship between genetic polymorphisms and susceptibilities to various types of cancers have intensified in recent years in the Department of Environmental Medicine and have resulted in successful collaborative NIH grant applications between investigators in the Epidemiology and Molecular Toxicology/Carcinogenesis Programs in the Department. Additionally, several members of the Department have long NIH funded track records in evaluating the epigenetic effects of DNA methylation at CpG islands in carcinogenesis models. Furthermore, increased efforts in these areas are reflected in Environmental Medicine's successful acquisition of a Superfund Basic Research Program Center Grant entitled "Genetic/Epigenetic Susceptibility to Superfund Chemicals." Other NIH funded projects by Department investigators involve the development of linkage maps with single nucleotide polymorphisms as markers to identify novel genes associated with toxicant induced disease. With this application, we propose to acquire a Pyrosequencer TM to be housed in the shared Molecular Facility Core of Environmental Medicine's longstanding NIEHS Center. This instrument is needed to increase the throughput and accuracy of genotyping for the multiple NIH funded genotyping studies by members of this Department. By increasing sample and loci number, these investigations will be much more sensitive in evaluating the effects of genetic polymorphisms on susceptibility to disease. Similarly, investigators studying the relationships between methylation status and carcinogenesis will be able to expand their analyses to include multiple CpG islands within a short stretch of DNA and will now be able to quantitatively estimate the percentage of hypermethylated nucleotides at individual islands. The NIH grant support obtained by the several research groups needing this instrument shows that they are conducting high-quality science; with the acquisition of the Pyrosequencer they will be able to perform more extensive and detailed investigations that will enable them to stay at the forefront in their research areas.