权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Large-scale expression analysis of natural antisense transcripts

天然反义转录本的大规模表达分析

基本信息

批准号：
8248786
负责人：
Xijin Ge
金额：
$ 20.54万
依托单位：
SOUTH DAKOTA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8248786
关键词：
Biological Process Code Communities Complement Complementary DNA Coupled DNA DNA Microarray Chip DNA Sequence Data Data Set Databases Disease Documentation Evolution Exhibits Exons Expressed Sequence Tags Gene Expression Gene Expression Profile Gene Expression Profiling Generations Genes Genetic Transcription Genomics Goals Histocompatibility Testing Human Investigation Jurkat Cells Label Lead Length Messenger RNA Methods Modeling Molecular Profiling Monitor Mus Mutation Noise Normal tissue morphology Northern Blotting Oligonucleotide Microarrays Oligonucleotides Orthologous Gene Outcome Pattern Physiological Pilot Projects Post-Translational Regulation Process Proteins Protocols documentation RNA Randomized Rattus Research Reverse Transcriptase Polymerase Chain Reaction Running Sampling Signal Transduction Single-Stranded DNA Specificity Testing Time Tissues Transcript Transcriptional Regulation base comparative cost density functional genomics genome-wide human tissue imprint insight mammalian genome novel pressure serial analysis of gene expression trait trend

项目摘要

Summary Recent studies have identified a large number of natural antisense transcripts that are transcribed from the genomic loci of well annotated genes, but from the opposite DNA strands. It is still unclear whether the majority of antisense transcripts are functional or merely transcriptional noise. We hypothesized that if antisense transcripts are related to certain physiological functions, they will exhibit variable levels of expression in different types of tissues and the pattern would tend to be evolutionarily conserved. By adapting commercial high-density oligonucleotide microarrays, we developed a cost-efficient approach that can monitor antisense expression across all exonic loci in mammalian genomes. Based on this approach, we will perform systematic profiling of antisense expression in various normal tissues in human, mouse and rat. Coupled with expression analysis of sense transcripts in the same samples, this will define a "double stranded" expression profile at the exon level. The data will be used for comparative analyses to determine if there are conserved patterns of tissue-dependent antisense expression. We will compare the correlations of expression patterns in orthologous pairs of antisense transcripts with the correlation of the expression pattern of permutated pairs. We will also determine whether highly expressed pairs of orthologous antisense transcripts have smaller DNA sequence divergence and whether orthologous pairs of antisense transcripts with smaller DNA sequence divergence tend to have (1) higher correlation in their expression profiles across various tissues, (2) smaller changes in expression level between species, and (3) smaller change in breadth of expression, similar to what have been observed in protein-coding genes. This could either provide substantial evidence for a selective purifying pressure on antisense transcription or favor a "neutral drift" model. The comprehensive datasets will also be used to identify novel antisense transcripts and tissue-specific antisense transcripts for further investigation. Such large-scale analysis of antisense expression will critically evaluate whether antisense transcription is a highly regulated process.

总结最近的研究已经鉴定了大量的天然反义转录物，从注释良好的基因的基因组位点转录，但从相反的DNA 股。目前还不清楚大多数反义转录物是否是功能性的，仅仅是转录噪音。我们假设，如果反义转录本与在某些生理功能中，它们将在不同的组织中表现出不同的表达水平。组织类型和模式在进化上趋于保守。通过调整商业高密度寡核苷酸微阵列，我们开发了一种具有成本效益的可以监测哺乳动物中所有外显子基因座的反义表达的方法基因组基于这种方法，我们将对反义核酸进行系统分析。在人、小鼠和大鼠的各种正常组织中表达。再加上表情分析相同样品中的正义转录物，这将定义“双链” 外显子水平的表达谱。这些数据将用于比较分析，确定是否存在组织依赖性反义表达的保守模式。我们将比较表达模式的相关性，在正交对，反义转录物与排列对表达模式的相关性。我们还将确定是否高表达的反义核酸对，转录本的DNA序列差异较小，具有较小DNA序列差异的反义转录物倾向于具有（1）较高的它们在不同组织中的表达谱的相关性，（2）种间表达水平，和（3）表达宽度的较小变化，类似于在蛋白质编码基因中观察到的情况。这可以提供反义转录的选择性纯化压力的实质性证据，或倾向于“中性漂移”模式。综合数据集还将用于确定新的反义转录物和组织特异性反义转录物，调查这种大规模的反义表达分析将批判性地评估反义转录是否是一个高度调控的过程。