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Single molecule detection of L1 insertions and intermediates

L1 插入和中间体的单分子检测

基本信息

批准号：
10662586
负责人：
BRADLEY Evan BERNSTEIN
金额：
$ 45.05万
依托单位：
DANA-FARBER CANCER INST
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10662586
关键词：
3&apos Flanking Region Admixture Benchmarking Biological Assay Biology Cataloging Catalogs Cell Nucleus Cells Cellular Assay Code Complement Complementary DNA Coupled DNA DNA Insertion Elements DNA Transposable Elements Data Data Analyses Detection Development Disease Elements Epigenetic Process Event Gene Frequency Genetic Variation Genome Genomic DNA Genomics Goals Heritability High-Throughput Nucleotide Sequencing Human Human Genetics Hybrids In Situ Inherited Laboratories Long Interspersed Elements Malignant Neoplasms Maps Methods Methylation Molecular Biology Molecular Computations Mosaicism Normal tissue morphology Phase Population Procedures Production Proteins Quality Control RNA Reaction Repression Research Personnel Retrotransposition Retrotransposon Reverse Transcription Sensitivity and Specificity Single Nucleotide Polymorphism Site Somatic Mutation Sorting Source Standardization Technology Tissues Validation Variant computational pipelines data analysis pipeline experience genetic variant genome-wide genomic locus genomic tools human tissue innovation instrument method development multidisciplinary nanopore promoter scale up single cell technology single molecule technology development tool tool development transposon sequencing variant detection whole genome

项目摘要

Project Summary Transposable elements are major sources of heritable human genetic variation and can contribute to disease by causing somatic mutations. This application focuses on the development of genomic tools and technologies to assess the contributions of these transposons to somatic mosaicism in normal tissues. Specifically, we will develop tools and technologies to detect variants in long interspersed element-1 (LINE-1, L1) sequences. L1 is the only active self-propagating protein-coding transposon in humans. We each inherit a distinct complement of active L1 loci, each of which is typically repressed through methylation of its internal promoter. Here, we propose to develop single cell mapping approaches to detect de novo L1 insertions and integrate these with long-read sequencing approaches to reveal the epigenetic status of source elements. We will also pioneer highly innovative approaches to detect intermediates of the target primed reverse transcription (TPRT) reaction that gives rise to L1 insertion events. Our multidisciplinary team brings together investigators with expertise in retrotransposon biology and genetic variation; innovation in the field of epigenetics; and experience with molecular biology and computational genomics methods development. Our shared goal in this UG3/UH3 project is to provide enabling tools and technologies to the Somatic Mosaicism across Human Tissues (SMaHT) Network.

项目总结