High Throughput DNA Sequencer

描述（由申请人提供）：我们拟向Illumina购买一套Solexa基因组分析系统。高通量序列数据将对校园研究产生积极影响。21名研究人员将能够在以下领域开展项目：1)基因组重测序，以确定细菌毒力决定因素，并将人类基因变异与疾病易感性联系起来；2)蛋白质与染色体DNA在整个基因组中的相互作用，以了解转录和表观遗传调控；3)全基因组基因表达，使我们能够全面了解从编码序列到非编码rna的转录过程。与现有技术相比，高通量DNA序列技术有两个显著的优势。首先，数据的收集是如此有效，以至于实验设计的根本改变成为可能，例如，允许对细菌基因组进行快速重测序，以获得与毒力相关的变异，或对人类基因组片段进行重测序，以进行SNP关联研究。其次，测序的大多数应用较少依赖于已知的信息，而微阵列是另一个主要的全基因组分析工具，它完全依赖于目标基因组序列的知识，或者在一些基因表达阵列的情况下，也依赖于转录的信息，甚至是剪接的信息。测序仪将被添加到现有的DNA和蛋白质微阵列设备中，形成UCI基因组学核心设备。校园已承诺提供资金，以完成Solexa仪器的购买和延长保修期，并购买必要的配件设备，并雇用全职技术人员和兼职系统管理员来为这次扩展提供人员。收购测序仪将对这个快速发展的加州大学校园的研究和培训产生高度积极的影响。公共卫生相关性：来自整个校园的研究人员联盟提议从Illumina获得用于UCI基因组学核心设施的Solexa高通量测序仪。高通量测序极大地增加了在一次实验操作中可以收集的序列量。将该仪器加入核心设施将使令人兴奋的生物医学研究成为可能。项目包括对整个细菌基因组进行测序以发现毒性决定因素，对人类基因组进行分析以确定与疾病相关的序列变异，确定人类基因组中与癌症相关的调节蛋白结合以控制基因表达的位点，以及对绵羊肺癌模型中基因表达变化进行量化。

DESCRIPTION (provided by applicant): We propose to purchase a Solexa Genome Analyzer System from Illumina. High throughput sequence data will positively impact campus research. Twenty-one investigators will be enabled to perform projects in the areas of: 1) genome resequencing to identify bacterial virulence determinants and to correlate human gene variants with disease susceptibility; 2) interaction of proteins with chromosomal DNA throughout the genome in order to understand transcriptional and epigenetic regulation; and 3) genomewide gene expression to enable understanding of the comprehensive picture of transcription from coding sequences to noncoding RNAs. High throughput DNA sequence technologies have two very significant advantages over current technologies. First, data are collected so efficiently that fundamental changes in experimental design are enabled, for example by allowing rapid resequencing of bacterial genomes for variations association with virulence or resequencing segment of the human genome for SNP association studies. Second, most applications of sequencing are less dependent on what is already known than microarrays, the other major genome wide analysis tool which is completely dependent upon knowledge of target genome sequence or in the case of some gene expression arrays, also dependent on knowledge about what is transcribed and even what is spliced. The sequencer will be added to the current DNA and Protein MicroArray Facility to form a UCI Genomics Core Facility. Funds have been committed by the campus to complete purchase of the Solexa instrument and extended warranties and purchase the necessary accessory equipment, and to hire a full time technician and part time systems administrator to staff this expansion. Acquisition of the sequencer will have a high positive impact on research and training at this rapidly growing UC campus. PUBLIC HEALTH RELEVANCE: A consortium of investigators from across campus proposes to acquire a Solexa high throughput sequencer from Illumina for the UCI Genomics Core Facility. High throughput sequencing dramatically increases the amount of sequence which can be collected in one experimental operation. Addition of this instrument to the Core Facility will enable exciting biomedical research. Projects include sequencing entire bacterial genomes to discover virulence determinants, analysis of human genomes to identify sequence variants associated with disease, identification of sites across the human genome where cancer-related regulatory proteins bind to control gene expression, and quantification of changes in gene expression in a sheep model for lung cancer.