Novel insight into stability and change in a basal vetebrate genome

对基础脊椎动物基因组稳定性和变化的新见解

基本信息

批准号：
7676260
负责人：
Jeramiah James Smith
金额：
$ 4.72万
依托单位：
BENAROYA RESEARCH INST AT VIRGINIA MASON
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：
2009-04-16 至 2010-08-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7676260
关键词：
Adult Affect Architecture Biological Biological Assay Biological Models Biology Cataloging Catalogs Cell Lineage Cells DNA DNA Sequence Rearrangement DNA Structure Data Analyses Data Set Development Disease Drug or chemical Tissue Distribution Embryonic Development Event Excision Family Fertilization Future Gene Expression Genes Genetic Recombination Genetic Transcription Genome Genomics Health Human Human Genome Knowledge Lampreys Maintenance Malignant Neoplasms Measures Mediating Methods Modeling Molecular Molecular Target National Human Genome Research Institute Nucleic Acid Regulatory Sequences Organogenesis Petromyzon marinus Plant Roots Regulation Research Research Training Resources Screening procedure Sequence Analysis Site Somatic Cell Structure System Testing Testis Time Tissues Translating United States National Institutes of Health Vertebrate Biology Whole-Genome Shotgun Sequencing base cancer type comparative functional genomics functional outcomes genome sequencing genome-wide hatching insight interest neuronal cell body novel progenitor programs vertebrate genome

Adult Affect Architecture Biological Biological Assay Biological Models Biology Cataloging Catalogs Cell Lineage Cells DNA DNA Sequence Rearrangement DNA Structure Data Analyses Data Set Development Disease Drug or chemical Tissue Distribution Embryonic Development Event Excision Family Fertilization Future Gene Expression Genes Genetic Recombination Genetic Transcription Genome Genomics Health Human Human Genome Knowledge Lampreys Maintenance Malignant Neoplasms Measures Mediating Methods Modeling Molecular Molecular Target National Human Genome Research Institute Nucleic Acid Regulatory Sequences Organogenesis Petromyzon marinus Plant Roots Regulation Research Research Training Resources Screening procedure Sequence Analysis Site Somatic Cell Structure System Testing Testis Time Tissues Translating United States National Institutes of Health Vertebrate Biology Whole-Genome Shotgun Sequencing base cancer type comparative functional genomics functional outcomes genome sequencing genome-wide hatching insight interest neuronal cell body novel progenitor programs vertebrate genome

展开

项目摘要

DESCRIPTION (provided by applicant): The broad objectives of this proposal are to elucidate the mechanisms that promote stability and change within vertebrate genomes. This knowledge is critical for understanding how the integrity of information encoded in the human genome is maintained and passed from cell to cell. Disruption of the numerous mechanisms that participate in the maintenance of genome structure is the root cause of many types of cancers and other genomic disorders. Many complimentary systems will need to be developed in order to more fully appreciate the diversity of mechanisms that participate in the maintenance of genome integrity, and mediate the rearrangement of DNA sequences. Indeed, the NIH has recognized the importance of developing non-mammalian model systems for comparative and functional genomic studies. The sea lamprey (Petromyzon marinus) is emerging as an attractive system for understanding the fundaments of vertebrate biology and was chosen by the NIH and NHGRI for whole genome sequencing, in order to facilitate further research using this important vertebrate lineage. This proposal builds on recently experimental developments that reveal the lamprey's novel genome biology. The lamprey undergoes dramatic changes in the architecture of its genome that occur as a feature of its normal development. This results in a situation wherein nearly every somatic tissue possesses a genome that is dramatically different from its germline precursor (i.e.sperm). These rearrangements occur at a massive (genome-wide) scale, are highly predictable, and are regulated during normal development. The specific aims of this proposal are to expand this newly discovered information about the lamprey genome such that we can begin to understand the molecular causes and consequences of these rearrangements in lamprey and ultimately translate these into a better understanding of the mechanisms by which rearrangements of the human genome are and can be regulated. LAY SUMMARY: Tight maintenance of genome structure is critical for maintenance of health and survival. Some exceptional species undergo dramatic changes in their genome structure that mimic disease causing changes. Proposed research is targeted at the genome of one of these species (the sea lamprey) and strives to better understand how such dramatic changes are regulated and affect the biology of this non- human model of basal vertebrate development.

描述（由申请人提供）：该提案的广泛目标是阐明促进脊椎动物基因组内稳定性和变化的机制。这种知识对于理解人类基因组中编码的信息的完整性如何维持并传递到细胞到细胞至关重要。参与基因组结构维持的众多机制的破坏是许多类型的癌症和其他基因组疾病的根本原因。将需要开发许多免费系统，以便更充分地理解参与基因组完整性的机制的多样性，并介导DNA序列的重排。实际上，NIH认识到开发非哺乳动物模型系统进行比较和功能基因组研究的重要性。 Sea Lamprey（Petromyzon Marinus）成为一种有吸引力的系统，用于理解脊椎动物生物学的基础，并由NIH和NHGRI选择整个基因组测序，以便使用这项重要的脊椎动物线索来促进进一步的研究。该提案建立在最近的实验发展，揭示了lamp带的新型基因组生物学。七lamp虫经历了其基因组结构的巨大变化，这是其正常发育的特征。这导致了几乎每个体细胞组织具有与其生殖线前体（即植物）截然不同的基因组的情况。这些重排以较大的（全基因组）量表发生，高度可预测，并且在正常发育过程中受到调节。该提案的具体目的是扩大有关七lamp鼠基因组的新信息，以便我们可以开始理解这些重排的分子原因和后果，并最终将其转化为对人类基因组重新排列的机制的更好理解，可以调节和可以调节人类基因组的重排。摘要摘要：严格维持基因组结构对于维持健康和生存至关重要。一些例外物种的基因组结构发生了巨大变化，导致疾病导致变化。拟议的研究针对这些物种之一（海七lamp虫）的基因组，并致力于更好地了解这种戏剧性变化如何受到调节并影响这种基础脊椎动物发育的非人类模型的生物学。