Genome Dynamics: Evolution, Organization and Function

我们用近交系小鼠进行的初步研究表明，哺乳动物的基因组包含广泛的、区域性的 随着进化时间的推移聚合在一起以促进共同遗传的功能相关元件的结构域 以及在功能相关基因上相容的等位基因集的存活率，以及 分离的染色体以一种明显的非随机方式相互作用，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是不同的， 在时间上它的进化和传承。 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，我们建议扩大我们的 从进化的角度将基因组动力学作为一个完整的系统进行研究。这需要 在我们将生成的大型数据集上使用计算方法来描述 基因组组织、基因表达、表型决定和重组的影响 确定共适应等位基因组遗传的热点。通过开发这些项目的详细地图 互动，我们可以评估潜在的原则。 我们将制定培训和外展计划，使我们的信息和工具可供 整个研究界并开始努力促进这一研究领域的发展，采取 在相关努力中利用杰克逊实验室的持续计划。推动长远发展 这一努力领域的发展，除了聚集在一起追求 在这个项目中，我们正在招聘几名年轻的教师，以便他们的相关工作能够蓬勃发展 随着时间的推移。 我们的项目旨在提高我们发现分子机制的研究能力。 潜在的人类健康和疾病。基因组科学的最新进展清楚地表明 达成这些认识是在改进预防和治疗方面迈出的有力一步 对于我们最常见的疾病，包括癌症，心脏病，免疫和神经疾病 系统。

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 endeavour, 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.