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Investigation of noncoding variation in human pancreatic islets and their develop

人胰岛非编码变异的研究及其发展

基本信息

批准号：
8827485
负责人：
Michael Lee Stitzel
金额：
$ 24.9万
依托单位：
JACKSON LABORATORY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-20 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8827485
关键词：
Address Adult Affect Alleles Beta Cell Binding Biological Assay Biological Models Blindness Blood Glucose Blood Vessels Cardiovascular Diseases Cell Differentiation process Cell Line Cells Chromatin Chromosomes Code Collaborations Complex Data Deoxyribonucleases Development Diabetes Mellitus Disease Distal EP300 gene Economic Burden Elements Enhancers Environment Epigenetic Process Failure Foundations Functional RNA Functional disorder Funding Gene Expression Generations Genes Genetic Genetic Enhancer Element Genetic Risk Genetic Variation Genome Genotype Goals Health Histone H3 Human Hypersensitivity In Vitro Individual Insulator Elements Insulin Insulin Resistance Investigation Islet Cell Islets of Langerhans Kidney Failure LacZ Genes Lead Letters Luciferases Measures Mediator of activation protein Methylation Molecular Molecular Conformation Morbidity - disease rate Mus Neurologic Non-Insulin-Dependent Diabetes Mellitus Nucleic Acid Regulatory Sequences Pancreas Participant Pattern Peripheral Nervous System Diseases Phase Phenotype Proteins Protocols documentation Public Health RNA Reagent Regulatory Element Reporter Research Personnel Research Project Grants Risk Risk Factors Role Sampling Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Therapeutic Intervention Tissues Training Activity Transcriptional Silencer Elements United States Variant base cell type chromatin immunoprecipitation cohesin cost diabetes risk genetic association genome wide association study genome-wide health economics histone modification induced pluripotent stem cell islet mortality pancreatic islet function precursor cell promoter spatiotemporal stem

项目摘要

Title: Investigation of noncoding variation in human pancreatic islets and their developmental precursors. The goal of this research project is to understand the role of genetic variation in non- protein coding, regulatory regions of the genome in human pancreatic islet function and dysfunction. Insulin-secreting cells in the islet are responsible for maintaining normal blood glucose levels. Type 2 diabetes (T2D) results from progressive failure of these cells to secrete insulin in the face of increasing blood glucose levels and is the cause of substantial morbidity and mortality in the United States and worldwide. Development of T2D involves complex interactions between an individual's genes and environment. Genetic association studies have identified approximately 40 regions in the genome that confer risk of developing T2D. The majority of these regions does not contain coding sequence variants, but instead contains non-coding variants. This project uses genome- wide chromatin profiling to identify the critical regulatory elements that contribute to T2D by determining which of the candidate regulatory regions function as enhancers, silencers, or insulators in human islets (Specific Aim 1) and which elements contain variants that alter gene expression in adult human islets (Specific Aim 2) or in pancreatic precursor cells (Specific Aim 3). Completion of these aims will provide detailed functional annotation of enhancer, silencer, and insulator elements, identify key regulatory element-promoter interactions, and identify how T2D-associated and other variants alter their function in human pancreatic precursor or mature islet cells.

题目：研究人类胰岛的非编码变异