Novel insight into stability and change in a basal vetebrate genome

描述（由申请人提供）： 这个提议的主要目标是阐明促进脊椎动物基因组稳定和变化的机制。这一知识对于理解人类基因组中编码的信息的完整性是如何保持并从细胞传递到细胞的至关重要。参与维持基因组结构的许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。为了更充分地了解参与维持基因组完整性和介导DNA序列重排的机制的多样性，需要开发许多互补系统。事实上，NIH已经认识到开发非哺乳动物模型系统用于比较和功能基因组研究的重要性。 海七鳃鳗（Petromyzon marinus）正在成为一个有吸引力的系统，用于了解脊椎动物生物学的基础，并被NIH和NHGRI选择进行全基因组测序，以促进使用这一重要的脊椎动物谱系的进一步研究。这项建议建立在最近的实验发展，揭示了七鳃鳗的新基因组生物学。七鳃鳗经历了戏剧性的变化，其结构的基因组发生的一个特点，其正常发展。这导致几乎每个体细胞组织都具有与其生殖系前体（即精子）显著不同的基因组的情况。这些重排发生在大规模（全基因组）范围内，具有高度可预测性，并在正常发育过程中受到调节。这项建议的具体目标是扩大这一新发现的信息七鳃鳗基因组，使我们可以开始了解分子的原因和后果，这些重新安排七鳃鳗，并最终转化为更好地了解机制，其中重新安排的人类基因组是和可以调节。 基因组结构的紧密维持对于维持健康和生存至关重要。一些特殊的物种在其基因组结构上发生了巨大的变化，这些变化模仿了引起疾病的变化。拟议的研究针对的是这些物种之一（海七鳃鳗）的基因组，并努力更好地了解这种戏剧性的变化是如何调节和影响这种基础脊椎动物发育的非人类模型的生物学的。

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.