Illumina iScan System for the OMRF Microarray Research Facility

描述(由申请人提供)： 项目摘要/摘要我们为一个两用微阵列平台申请资金，这是一个带有Illumina公司Autoloader 2的iScan(R)系统。该仪器将执行高密度全基因组关联和甲基化研究、定制单核苷酸多态(SNP)检测和基因组规模的表达谱分析。所要求的仪器将取代同样来自IllLumina，Inc.的过时和租赁的BeadStation“，该公司现在被排队的项目淹没，将于2010年7月1日归还给设备所有者。所请求的仪器系统比租用的仪器快10倍。新仪器将具有更高的生产能力，将更有效地为我们NIH资助的项目服务。建议的主要用户由NIH资助的旨在了解系统性红斑狼疮、其亚型和相关的自身免疫性风湿病的工作统一起来。收集了30,000多名受试者，通过基因分型和基因表达分析来解释狼疮的遗传学。实验正在进行中，未来几个月将需要20,000个阵列读数。在接下来的四年里，预计&gt；100,000阵列读数将产生数十亿的基因类型和基因表达测量结果。这项工作通常需要很大的样本量(&gt；10,000)才能有足够的统计能力。除了广泛的精细作图提供的遗传定位外，遗传关联效应的跨祖先作图方法几乎总是有助于鉴定致病基因的多态。除了狼疮，我们NIH资助的研究人员社区还对其他表型感兴趣，包括干燥综合征、白塞病、结节病、类风湿性关节炎、糖尿病和恶性肿瘤。就这些参数而言，Illumina iScan(R)系统目前是最好的系统。用户不仅可以进行SNP检测和拷贝数变异，还可以进行基因组规模的基因表达研究。基因分型能力尤其重要，因为计划进行具有100多万个多态的全基因组关联研究(GWAS)，以及从1536个到超过200,000个单核苷酸多态(SNP)的定制阵列。通过在一些单一实验中支持多个研究人员的小型和大型项目(包括超过14,000个样本)，我们的主要瓶颈是阵列扫描时间。配备了自动加载器样本的iScan系统将使我们的容量增加近40倍。这一能力将允许同时完成来自大量研究人员的多个项目，以确定新的疾病基因，并在NIH资助的项目中检查与疾病相关的途径。我们的调查人员拥有资金、专业知识和机构支持，可以充分利用所要求的仪器和这项技术将提供的信息。这项技术将最大限度地发挥其潜在价值，推进这项由美国国立卫生研究院支持的研究。

DESCRIPTION (provided by applicant): Project Summary/Abstract We request funding for a dual-purpose microarray platform, an iScan(R) system with Autoloader 2 by Illumina, Inc. This instrument will perform high-density genome wide association and methylation studies, custom single nucleotide polymorphism (SNP) detection and genome-scale expression profiling. The requested instrument will replace an outdated and leased BeadStation", also from Illlumina, Inc., which is now overwhelmed with queued projects and which will revert to the equipment owner on July 1, 2010. The requested instrument system is >10 times faster than the leased instrument. The new instrument will with higher throughput capacity will serve our NIH-funded projects more efficiently. The proposed Major Users are unified by their NIH funded work directed toward understanding systemic lupus erythematosus, its sub-phenotypes, and related autoimmune rheumatic disorders. Over 30,000 subjects have been collected to explain the genetics of lupus by genotyping and gene expression analysis. Experiments are underway that will require >20,000 array readings in the next few months. In the subsequent four years >100,000 array readings are anticipated generating billions of genotypes and gene expression measurements. This work often requires large sample sizes (>10,000) in order to have adequate statistical power. In addition to the genetic localization available from extensive fine mapping, the approach of trans-ancestry mapping of genetic association effects virtually always contributes toward the identification of the causative polymorphisms. In addition to lupus, other phenotypes are of interest to our NIH funded community of investigators including Sjvgren's syndrome, Behcet's disease, sarcoidosis, rheumatoid arthritis, diabetes, and malignancies. The Illumina iScan(R) system is currently the best system with respect to these parameters. Users may perform not only SNP detection and copy number variation but also genomic scale gene expression studies. The genotyping capabilities are especially important as both genome wide association studies (GWAS) with over 1 million polymorphisms are planned, as well as custom arrays from 1536 to over 200,000 single nucleotide polymorphisms (SNPs). By supporting multiple investigators in both small and large projects consisting of more than 14,000 samples in some single experiments our primary bottleneck is array scanning time. The iScan system equipped with a sample autoloader will increase our capacity nearly 40 fold. This capacity will allow the simultaneous completion of multiple projects from a large number of investigators to identify novel disease genes and examine disease related pathways in NIH funded projects. Our investigators have the funding, expertise and institutional support to fully exploit the requested instrument and the information this technology will provide. This technology will be used to its maximum potential value in advancing this NIH supported research.