Transcripts and Functions Targeted by Non-coding RNAs in Palate Development

上颚发育中非编码 RNA 靶向的转录本和功能

基本信息

批准号：
9165356
负责人：
Junichi Iwata
金额：
$ 23.1万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9165356
关键词：
Accounting Affect Anterior Base Sequence Bioinformatics Biological Cell Count Cell Proliferation Cells Cleft Palate Code Complex DNA Sequence Data Data Analyses Data Set Databases Development Diagnosis Disease Early Diagnosis Embryo Environmental Risk Factor Ethnic Origin Etiology Event Family Future Gender Gene Expression Gene Expression Regulation Gene Mutation Gene Targeting Genes Genetic Genetic Transcription Genetic study Genome Goals Health Hour Human Image In Situ Hybridization Individual Internet Lateral Lead Linear Models Link Maps Medial Mesenchymal Messenger RNA Meta-Analysis MicroRNAs Morphogenesis Mus Organ Palate Pattern Phenotype Play Population Prevalence Prevention Process Proteins Quality Control RNA RNA-Protein Interaction Reading Reverse Transcriptase Polymerase Chain Reaction Role Scanning Electron Microscopy Specificity Staging Structure Technology Testing Therapeutic Tissues Transact Transcript Translating Untranslated RNA Variant base design differential expression genetic approach genetic information genome-wide human genome sequencing insight overexpression palatogenesis prevent public health relevance research study systematic review tool transcriptome transcriptome sequencing

Accounting Affect Anterior Base Sequence Bioinformatics Biological Cell Count Cell Proliferation Cells Cleft Palate Code Complex DNA Sequence Data Data Analyses Data Set Databases Development Diagnosis Disease Early Diagnosis Embryo Environmental Risk Factor Ethnic Origin Etiology Event Family Future Gender Gene Expression Gene Expression Regulation Gene Mutation Gene Targeting Genes Genetic Genetic Transcription Genetic study Genome Goals Health Hour Human Image In Situ Hybridization Individual Internet Lateral Lead Linear Models Link Maps Medial Mesenchymal Messenger RNA Meta-Analysis MicroRNAs Morphogenesis Mus Organ Palate Pattern Phenotype Play Population Prevalence Prevention Process Proteins Quality Control RNA RNA-Protein Interaction Reading Reverse Transcriptase Polymerase Chain Reaction Role Scanning Electron Microscopy Specificity Staging Structure Technology Testing Therapeutic Tissues Transact Transcript Translating Untranslated RNA Variant base design differential expression genetic approach genetic information genome-wide human genome sequencing insight overexpression palatogenesis prevent public health relevance research study systematic review tool transcriptome transcriptome sequencing

展开

项目摘要

ABSTRACT The cause of cleft palate is influenced by multiple complex genetic and environmental factors. During palate morphogenesis, hundreds of gene expressions dramatically change at each embryonic stage. However, it is still largely unknown how these gene expressions are regulated. Recent studies reveal that non-coding RNAs (ncRNAs: 98% of transcriptome) affect the expression of genes encoded by coding RNAs (aka messenger RNAs, mRNAs) as well as the phenotype without altering the DNA sequence, and contribute to a number of diseases. Although most genetic information is transacted by proteins through mRNAs, the majority of the genome is transcribed into ncRNAs including microRNAs (miRs) and long non-coding RNAs (lncRNAs). We hypothesize that the proper control of ncRNAs, which play important roles in palate development, is crucial for the regulation of genes, due to the fact that their disruption causes cleft palate. To identify ncRNAs involved in palate development, we will analyze 1) FaceBase1 miR sequencing (miR-seq) datasets; 2) FaceBase1 mRNA microarray datasets; and 3) FaceBase1 RNA sequencing (RNA-seq) datasets, from the developing mouse palate. In addition, to predict ncRNAs involved in cleft palate from previous genetic studies in humans and mice, we will perform systematic review and meta-analyses for cleft palate causative genes. The findings by bioinformatics analyses will then be validated experimentally. Our specific aims are to 1) determine the genes and their functions regulated by miRs during palate development; 2) identify lncRNAs involved in palate development; and 3) determine the direct biological link of ncRNAs to the phenotype. This study will provide insight into the role of ncRNAs in palate development and suggest possible strategies for the diagnosis and prevention of cleft palate.

抽象的 left裂的原因受到多个复杂的遗传和环境因素的影响。在味蕾期间形态发生，数百个基因表达在每个胚胎阶段都发生了巨大变化。但是，是这些基因表达如何调节仍然未知。最近的研究表明，非编码RNA （NCRNA：转录组的98％）影响通过编码RNA（又称Messenger）编码的基因的表达 RNA，mRNA）以及表型而不改变DNA序列，并有助于多个疾病。尽管大多数遗传信息都是通过mRNA通过蛋白质进行的，但大多数基因组被转录为NCRNA，包括microRNA（MIR）和长非编码RNA（LNCRNA）。我们假设对NCRNA的适当控制（在papepenting中起重要作用）对于基因的调节，因为它们的破坏会导致口感cle裂。识别涉及的ncRNA 口感开发，我们将分析1）facebase1 mir测序（mir-seq）数据集； 2）facebase1 mRNA 微阵列数据集； 3）来自发育中的鼠标口感。此外，要预测人类以前遗传研究和小鼠，我们将对left裂性基因进行系统的审查和荟萃分析。结果然后，生物信息学分析将通过实验验证。我们的具体目的是1）确定基因及其功能由mir在口感发育过程中受到调节； 2）识别涉及味觉的lncrnas 发展; 3）确定NCRNA与表型的直接生物学联系。这项研究将提供深入了解NCRNA在pa de发育中的作用，并提出了诊断的可能策略预防裂纹。