Genome Dynamics: Evolution, Organization and Function

描述（由申请人提供）：我们使用近交系小鼠的初步研究表明，哺乳动物基因组包含广泛的功能相关元件的区域结构域，这些结构域在进化过程中合并，以促进功能相关基因处相容等位基因组的共遗传和存活，并且不同染色体上的结构域以明显非随机的方式相互作用，形成无标度网络。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变化，其进化和遗传在时间上变化。利用计算生物学家，分子生物学家和遗传学家的团队，我们建议从进化的角度扩展我们的研究作为一个综合系统的基因组动力学。这需要在我们将生成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组遗传中的影响之间的相互作用。通过绘制这些相互作用的详细地图，我们可以评估基本原理。我们将开发培训和推广计划，使我们的信息和工具提供给广大的研究界，并开始努力促进这一研究领域的发展，利用杰克逊实验室的相关工作的持续计划。为了促进这一奋进的长期发展，除了已经走到一起追求这一计划的既定教师，我们正在招募几个年轻的教师，使他们的相关努力可以随着时间的推移蓬勃发展。我们的项目旨在提高我们的研究能力，以发现人类健康和疾病的分子机制。基因组科学的最新进展清楚地表明，达成这些理解是在开发针对我们最常见疾病（包括癌症、心脏病以及免疫和神经系统疾病）的改进预防和治疗方面向前迈出的有力一步。

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.