INVESTIGATING THE ASSOCIATION BETWEEN HYPOMETHYLATION OF TRANSPOSABLE ELEMENTS

研究转座元件低甲基化之间的关联

• 批准号: 8357854
• 负责人: Lucia Carbone
• 金额: $ 3.63万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357854
• 关键词: Acute Myelocytic Leukemia; Algorithms; Bioinformatics; Biological Models; Blast Cell; Chromosomal Rearrangement; Chromosomes; Custom; DNA Sequence; DNA Sequence Rearrangement; DNA Transposable Elements; Elements; Epigenetic Process; Funding; Genome; Genomics; Grant; Hylobates Genus; Libraries; Malignant - descriptor; Malignant Neoplasms; Maps; Measures; Methylation; Mutation; National Center for Research Resources; Normal Cell; Patients; Primates; Principal Investigator; Repetitive Sequence; Reporting; Research; Research Infrastructure; Resources; Source; Testing; United States National Institutes of Health; Variant; base; bisulfite; cost; next generation; structural genomics

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project will study the relationship between global hypomethylation, activation of Transposable Elements (TEs), and chromosomal rearrangements in cancer. TEs are DNA sequences that can move and insert randomly in the genome causing mutations, including large-scale chromosomal rearrangements. CpG methylation is the main mechanism to repress these elements and limit genomic damage. Both reduction of CpG-methylation (hypomethylation) and chromosomal rearrangements are common in cancer, although a causal relationship is unclear at this point. Using gibbons, which display an unusually high rate of evolutionary chromosome changes and therefore are an excellent model system for studying mechanisms of genomic structural variation, we have shown an association between undermethylated TEs (Alus) and chromosomal breakpoints. In this pilot, we will look for a similar association in cancer (somatic) chromosomal breakpoints and test different approaches based on next-generation sequencing on one Acute Myeloid Leukemia (AML) patient. We will generate short and long-range paired-end Illumina libraries from the blasts and normal cells of the patient in order to map the somatic rearrangements. Furthermore, we will measure CpG-methylation of TEs using whole-genome bisulfite sequencing. Custom algorithms and bioinformatics workflows will be generated to identify the epigenetic state of repetitive elements nearby breakpoints and study changes related to malignant transformation. As this grant was recently been funded, there is no progress to report at this point.

这个子项目是利用这些资源的众多研究子项目之一