Genome Dynamics: Evolution, Organization and Function

描述(申请人提供)：我们使用近交系小鼠进行的初步研究表明，哺乳动物基因组包含广泛的、区域性的功能相关元件区域，随着进化时间的推移，这些区域结合在一起，促进功能相关基因上相容的等位基因集的共同遗传和生存，并且不同染色体上的区域以明显的非随机方式相互作用，形成无尺度网络。实际上，哺乳动物基因组是一个动态系统，其组织和表达在空间上是不同的，进化和遗传在时间上也是不同的。利用一个由计算生物学家、分子生物学家和遗传学家组成的团队，我们建议从进化的角度将基因组动力学作为一个完整的系统来扩展我们的研究。这需要在我们将产生的大数据集上使用计算方法来描述基因组组织、基因表达、表型确定和重组热点在确定共适应等位基因集的遗传中的影响之间的相互作用。通过开发这些相互作用的详细地图，我们可以评估基本原则。我们将制定培训和外展计划，向整个研究社区提供我们的信息和工具，并开始努力促进这一研究领域的发展，利用杰克逊实验室在相关努力中的持续计划。为了促进这一领域的长期发展，除了聚集在一起从事这一项目的现有教员外，我们正在招聘几名年轻教员，以便他们的相关努力能够随着时间的推移而蓬勃发展。我们的项目旨在增强我们发现人类健康和疾病潜在分子机制的研究能力。基因组科学的最新进展表明，达成这些理解是朝着改进我们最常见疾病的预防和治疗迈出的有力一步，这些疾病包括癌症、心脏病以及免疫和神经系统疾病。

DESCRIPTION (provided by applicant): Our preliminary studies using inbred mice show that mammalian genomes contain extensive, regional domains of functionally related elements that coalesced over evolutionary time to promote the coinheritance and survival of compatible sets of alleles at functionally related genes, and that domains on separate chromosomes interact in a distinctly non-random manner, forming scale-free networks. In effect, the mammalian genome is a dynamic system which varies spatially in its organization and expression and temporally in its evolution and inheritance. Using a team of computational biologists, molecular biologists and geneticists, we propose extending our studies of genome dynamics as an integrated system from an evolutionary perspective. This requires using computational approaches on large data sets we will generate to describe the interactions between genome organization, gene expression, phenotype determination and the impact of recombination hotspots in determining inheritance of co-adapted sets of alleles. By developing detailed maps of these interactions we can evaluate the underlying principles. We will develop training and outreach programs to make our information and tools available to the research community at large and initiate efforts to promote the development of this research area, taking advantage of The Jackson Laboratory's sustained programs in related efforts. To promote the long-term growth of this field of endeavor, in addition to the established faculty that have come together to pursue this program, we are recruiting several younger faculty so that their related efforts can flourish and develop over time. Our projects are designed to enhance our research capabilities for discovering the molecular mechanisms underlying human health and disease. Recent advances in genomic sciences have made it clear that reaching these understandings is a powerful step forward in developing improved prevention and therapy for our most common ills, including cancer, heart disease, and disorders of the immune and neurological systems.