Analysis of inter- and intra-species genetic diversity and their function with a focus on mobile elements

生物体如何在同一物种和不同物种的个体之间在遗传水平上产生差异，以及这些差异如何导致不同的生物学特征，代表了具有重要意义的基本生物学问题。解决这些问题是我研究计划的长期目标，我们将在本资助期内开展四项相互关联的研究，每项研究都解决刚才提出的中心问题的一个特定方面。研究1将开发一套参考序列数据库和工具，以改善对个人基因组结构变异的分析。结构变异是基因组序列的大规模重排，主要包括拷贝数变异、易位、倒位和移动的元件插入。这些变异已被认为是与表型变异高度相关的遗传变异，但它们的检测和表征一直非常具有挑战性。我们将通过开发结构变体参考数据库和相关工具来解决当前方法的不一致性。我还将通过构建现代人类祖先的参考基因组来解决当前人类参考基因组序列在定义变体方面的不足。研究2将深入评估灵长类动物之间、现代人和古代人之间以及现代人之间的移动的因素所造成的遗传差异。移动的元件是一组可以在基因组中移动或扩展的遗传元件。它们在大多数基因组中占很大比例，是种内和种间遗传多样性的主要来源，是一种结构变异形式。本研究应用我们为人类研究开发的计算基因组学方法，分析了非人灵长类动物和古人类的7个基因组。研究3将评估移动的元素衍生的遗传多样性的功能。我们将通过研究移动的元件的转录活性以及它们对基因转录和相关细胞过程（如选择性剪接）的贡献来解决这个长期问题。研究4将应用从灵长类动物研究开发的研究策略来分析产精油的熏衣草。基于我们最近获得的熏衣草基因组序列，我们将提供一个完整的遗传组成的注释，并分析熏衣草品种和物种之间的遗传多样性的类型和数量。这些信息有助于了解与精油生产相关的遗传机制，并为熏衣草指纹图谱和育种提供遗传标记。在解决这些重要的生物学问题的同时，拟议的研究为基因组学研究社区建立了宝贵的资源。此外，该计划将发展多学科合作，并在基因组学和生物信息学的高度需求领域提供HQP培训。

How organisms develop differences at the genetic level among individuals of the same species and across species and how these differences lead to different biological traits represent fundamental biological questions with important implications. Addressing these questions is the long-term goal of my research program, and we will carry out four interconnected studies in this funding period, each addressing a specific aspect of the central questions just posed. Study 1 will develop a set of reference sequence databases and tools to improve analysis of structural variants in personal genomes. Structural variants are large genome sequence rearrangements, including mainly copy number variation, translocation, inversion, and mobile element insertion. These variants have been recognized as genetic variants highly relevant to phenotypic variation, but their detection and characterization have been very challenging. we shall address the current methodology insufficiencies by developing a structural variant reference database and related tools. I shall also address the shortfalls of current human reference genome sequence in defining variants by constructing a reference genome ancestral to modern humans. Study 2 will provide an in-depth assessment of the genetic differences contributed by mobile elements among primates, between modern and archaic humans, and among modern humans. Mobile elements are a group of genetic elements that can move or expand in a genome. They constitute a significant proportion of most genomes and represent a major source of intra- and inter-species genetic diversity as a form of structural variant. This study applies the computational genomics methodologies we developed for human study to analyzing 7 genomes of non-human primates and archaic humans. Study 3 will assess the functions of mobile element-derived genetic diversity. We shall address this long-term question by examining the transcriptional activity of mobile elements as well as their contribution to the gene transcripts and related cellular processes, such as alternative splicing. Study 4 will apply the research strategies developed from primate studies to the analysis of essential oil-producing lavenders. Based on the lavender genome sequence we recently generated, we shall provide a full annotation of the genetic composition and analyze the types and amounts of genetic diversity among lavender cultivars and species. Such information can help understand the genetic mechanisms related to essential oil production and provide genetic markers for lavender fingerprinting and breeding. While addressing these important biological questions, the proposed studies build valuable resources for the genomics research communities. Further, the program will develop multi-disciplinary collaborations and provides HQP training in the highly demanded areas of genomics and bioinformatics.