Germline sequence resources & analyses in a vertebrate model that undergoes PGR

描述(申请人提供)：七鳃鳗Petromyzon marinus是一种新兴的非哺乳动物模式生物，符合PA-07-457标准。基因组已经测序到9.1倍的覆盖率，组装程序已经公开可用。这一提议的推动力是基于我们对海鳗基因组动态性质的观察。我们最近发现，在胚胎发生的早期，海洋假单胞菌经历了大量的染色质减少，多达20%的体细胞基因组被丢弃。这项提案中提供的大量初步数据证实了这些损失，并重要地证实了我们之前的观察结果，即大片蛋白质编码序列也在发育中被消除。这些发现揭示了现有七鳃鳗基因组序列组装的一个严重缺陷。在这项应用中，我们建议生成和组装来自Marinus生殖系的DNA序列，这将为该物种提供一个全面改进的基因组组装。这项拟议的工作填补了这种有机体在序列知识方面的一个主要空白，因此对于几乎每个利用七鳃鳗作为主要模型或作为了解脊椎动物发育、生理学或基因组生物学基本特征的参考的实验室来说都是至关重要的。通过开发未采样区域的种子组装，改善体细胞和生殖系基因组组装的邻接性，交叉告知现有克隆资源，并注释基因组恒定和修饰区域中表达序列的位置，我们将极大地提高现有七鳃鳗基因组资源对群落的利用，并在这个非哺乳动物模型系统中了解更多关于程序性基因组重排的知识。 公共卫生相关性：七鳃鳗是一种新兴的非哺乳动物模式生物，已被广泛用于研究许多脊椎动物特有的特征，包括那些与人类健康相关的特征。然而，七鳗鱼基因组序列的不足，对研究这种生物的研究人员来说是一个很大的问题。因此，开发改良的七鳃鳗基因组序列对该社区来说是势在必行的。

DESCRIPTION (provided by applicant): The sea lamprey, Petromyzon marinus, is an emerging nonmammalian model organism that satisfactorily meets the criteria for PA-07-457. The genome has been sequenced to 9.1X coverage and an assembly is publicly available. The impetus for this proposal is based on our observations concerning the dynamic nature of the sea lamprey genome. We have recently shown that P. marinus undergoes substantial chromatin diminution with as much as 20% of its somatic genome being discarded during early embryogenesis. Extensive preliminary data presented in this proposal confirm these losses and importantly corroborate our prior observations that large swaths of protein-coding sequences are also being developmentally eliminated. These findings uncover a severe deficiency in the available lamprey genome sequence assembly. In this application we propose to generate and assemble DNA sequences from the P. marinus germline that will provide an overall improved genome assembly for this species. The proposed work fills a major gap in sequence knowledge for this organism and is therefore critical to nearly every lab that utilizes lamprey as a primary model or as a reference for understanding basal features of vertebrate development, physiology, or genome biology. By developing seeded assemblies of unsampled regions, improving contiguity of the somatic and germline genome assemblies, cross-informing existing clone resources, and annotating the location of expressed sequences within constant and modified regions of the genome, we stand to dramatically improve the utility of existing lamprey genome resources for the community and to learn much about programmed genome rearrangement in this nonmammalian model system. PUBLIC HEALTH RELEVANCE: The lamprey is an emerging nonmammalian model organism that has been utilized extensively to study many vertebrate-specific characteristics, including those of human health relevance. The inadequacy of the lamprey genome sequence, however, is highly problematic for researchers studying this organism. Development of an improved lamprey genome sequence is thus imperative for the community.