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：
7791283
负责人：
Xijin Ge
金额：
$ 20.56万
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 2013-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7791283
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 public health relevance serial analysis of gene expression trait trend

项目摘要

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: The present proposal represents an attempt to obtain comprehensive data on the expression of a certain type of novel genes that could interfere with ordinary protein- coding genes. We will study their expression patterns in various normal tissues of human, mouse and rat so that we could gain insight into their potential physiological function.

描述（由申请人提供）：最近的研究确定了大量自然反义转录本，这些转录物是从良好注释基因的基因组基因座转录的，但从相反的DNA链中。目前尚不清楚大多数反义转录本是功能性还是仅仅是转录噪声。我们假设，如果反义转录本与某些生理功能有关，则它们将在不同类型的组织中表现出可变的表达水平，并且该模式往往在进化上保守。通过调整商业高密度寡核苷酸微阵列，我们开发了一种经济高效的方法，可以监测哺乳动物基因组中所有外显子基因座的反义表达。基于这种方法，我们将对人，小鼠和大鼠的各种正常组织中的反义表达进行系统分析。再加上同一样品中的感觉转录本的表达分析，这将定义外显子级的“双链”表达谱。数据将用于比较分析，以确定是否存在组织依赖性反义表达的保守模式。我们将比较反义转录本的直系同源对中表达模式的相关性与置换对的表达模式的相关性。 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.这可以为反义转录的选择性纯化压力提供大量证据，或者有利于“中性漂移”模型。综合数据集还将用于识别新型的反义转录本和组织特异性的反义转录本以进行进一步研究。对反义表达的这种大规模分析将严格评估反义转录是否是一个高度调节的过程。公共卫生相关性：本提案代表了一种尝试获取有关某种类型的新型基因表达的全面数据，这些数据可能会干扰普通的蛋白质编码基因。我们将研究它们在人，小鼠和大鼠的各种正常组织中的表达模式，以便我们可以深入了解它们的潜在生理功能。