Genome-Wide Analysis of Gene Duplication in Vertebrates

描述：(申请人摘要)大规模复制，从染色体片段到整个基因组，然后发生突变被认为是一种主要的 推动脊椎动物功能多样性的力量。个别的例子 重复区域支持这一理论，但对哺乳动物的全基因组研究 基因复制和随后的功能多样化还没有 已尝试。更好地理解两者在功能上的相似性 复制的基因将极大地增强平行关系的力量 预测基因功能和了解遗传病。候选人的 长期的职业目标是在中国建立一个独立的研究项目 学术界，使用计算基因组学来研究基因复制在 哺乳动物基因组的进化、结构和功能。具体目标 目前的提案构成了该方案的第一步，并将 允许应聘者展示她的跨学科的可行性 接近。它们是(1)构造所有可辨别的空间有序集合 在小鼠和人类基因组中复制基因，并估计 每个重复；(2)开发识别算法，识别大数 衡量发生的复制并确定重新排列的顺序 这随后使它们支离破碎；(3)使用概率模型确定 对于重排，重复区域的空间组织在多大程度上 保存；以及(4)用功能数据注释复制数据 为后续功能分化过程的研究做准备 复制。

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.