Genome-Wide Analysis of Gene Duplication in Vertebrates

描述：（申请人的摘要）大规模重复，从染色体 片段到整个基因组，随后的突变被认为是一个主要的 推动脊椎动物功能多样性的力量。孤立的例子 重复的区域支持这一理论，但对哺乳动物的全基因组研究表明， 基因复制和随后的功能多样化还没有被 企图。更好地理解 复制的基因将大大增强旁系同源关系的力量， 预测基因功能和了解遗传疾病。候选人的 长期的职业目标是建立一个独立的，研究计划， 学术界，使用计算基因组学研究基因复制在 哺乳动物基因组的进化、结构和功能。的具体目标 目前的建议构成了该计划的第一步，并将 允许候选人证明她的跨学科的可行性 approach.它们是（1）构造所有可辨别的空间有序集 在小鼠和人类基因组中复制基因，并估计 （2）开发算法来识别大量的 规模重复发生，并确定重组的顺序 （3）使用概率模型来确定 重新排列，重复区域的空间组织在多大程度上 保存;以及（4）用函数数据注释复制数据， 研究功能分化过程的准备 重复。

DESCRIPTION: (Applicant's Abstract) Large scale duplication, from chromosomal fragments to the entire genome, followed by mutation is considered a major force driving functional diversity in vertebrates. Isolated examples of duplicated regions support this theory, but a genome-wide study of mammalian gene duplication and subsequent functional diversification has not been attempted. A better understanding of the functional similarities between duplicated genes would greatly enhance the power of paralogous relationships in predicting gene function and understanding genetic disease. The candidate's long-term career goal is to establish an independent, research program in academia, using computational genomics to study the role of gene duplication in the evolution, structure and function of mammalian genomes. The specific goals of the current proposal constitute the first step in this program and will allow the candidate to demonstrate the feasibility of her interdisciplinary approach. They are (1) to construct a spatially ordered set of all discernible duplicated genes in the mouse and human genomes and to estimate the time of duplication for each; (2) to develop algorithms to identify the number of large scale duplications that took place and determine the sequence of rearrangements that subsequently fragmented them; (3) to determine, using probabilistic models of rearrangements, to what extent spatial organization of duplicated regions is preserved; and (4) to annotate the duplication data with functional data in preparation for studying the processes of functional differentiation following duplication.