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

点击翻译按钮获取中文摘要

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.