Repetitive DNA structure of the human genome

人类基因组的重复DNA结构

• 批准号: 7413422
• 负责人: PETER E WARBURTON
• 金额: $ 30.87万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7413422
• 关键词: 13q; 18p; 21q; Accounting; Affect; Age; Algorithms; Arabidopsis; Base Pairing; Bioinformatics; Biological; Biology; Cataloging; Catalogs; Chromosome Structures; Chromosomes; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 9; Chromosomes, Human, X; Chromosomes, Human, Y; Class; Code; Computer Analysis; Computer software; Computers; Cruciform DNA; Custom; DNA; DNA Sequence; DNA Sequence Rearrangement; DNA Structure; DNA Transposable Elements; DNA Transposons; DNA biosynthesis; Depth; Disease; Doctor of Philosophy; Elements; Event; Evolution; Extinction (Psychology); Family; Gametogenesis; Gene Conversion; Generations; Genes; Genetic Crossing Over; Genome; Genomics; Germ Cells; Health; Human; Human Chromosomes; Human Genome; Human Genome Project; Left; Length; Location; Meiosis; Meiotic Recombination; Methodology; Methods; Molecular; Molecular Analysis; Molecular Evolution; Mus; Mutation; Natural History; Numbers; Open Reading Frames; Pattern; Population; Positioning Attribute; Primates; Process; Proteins; Pseudogenes; Purpose; Range; Rate; Recording of previous events; Relative (related person); Research Personnel; Retrotransposon; Role; Satellite DNA; Scientist; Selfish DNA; Sex Chromosomes; Shapes; Stretching; Structure; Surveys; Tandem Repeat Sequences; Testis; Time; Today; Upper arm; Variant; X Chromosome; base; density; genome sequencing; genome-wide analysis; heuristics; human DNA sequencing; indexing; insight; male; neglect; novel; programs; size; stem; tool

DESCRIPTION (provided by applicant): The repetitive DNA structure of the human genome The recent completion of the human genome project gives today's scientists the privileged opportunity to provide, for the first and only time, a detailed comprehensive description of the structure of the human DNA sequence. Large parts of our genome remain relatively understudied, especially the repetitive DNA fractions, which account for greater than 45% of our total DNA sequence. Many important genomic turnover mechanisms contribute to the large accumulation of repetitive DNA in our genome, including genomic duplication, transposition, unequal crossing over, and gene conversion, which have a huge impact on the structure of our genome over the course of evolution. Therefore, we propose to undertake the first genome- wide survey and analysis of three distinct aspects of human repetitive DNA, by developing novel computer algorithms, genome analysis tools, and rigourous experimental approaches. 1) We propose to identify and characterize the complete catalogue of human inverted DNA repeats, which have been associated with many important genome functions such as DNA replication, meiotic crossover, and gene conversion. Our results have shown that the human X chromosome contains a preponderance of large highly homologous inverted repeats that contain testes genes. 2) We propose to investigate novel classes of tandemly repeated "satellite" DNA that contain human transposons. These are organized in multiple large arrays primarily in the pericentromeric regions of chromosomes, where rapid chromosome evolution takes place. We have identified and characterized a large family of tandem repeats composed almost entirely of rearranged MaLR LTR transposons, found on 8 different human chromosomes in arrays as large as 70kb. 3) We propose to perform a genome-wide analysis of human transposable elements (TE's) by analyzing the large number of nested transposon clusters where newer TE's have transposed into older TE's. We have developed unique methodology and computer algorithms that can locate and index all such transposon clusters in the human genome, and can derive a relative chronological order of human TEs over the course of evolution. This represents a completely novel method of studying molecular evolution that is not dependent on the assumption of a constant mutation rate (molecular clock). The studies proposed in this application will facilitate both computational and biological approaches to genomics and provide a unique analysis of a large and relatively neglected portion of our DNA sequence.

描述（由申请人提供）：人类基因组的重复DNA结构最近完成的人类基因组计划为当今的科学家提供了一个难得的机会，第一次也是唯一一次提供人类DNA序列结构的详细全面描述。我们基因组的大部分内容仍然相对未被充分研究，尤其是重复 DNA 片段，它占我们总 DNA 序列的 45% 以上。许多重要的基因组周转机制导致基因组中重复DNA的大量积累，包括基因组复制、转座、不等交换和基因转换，这些机制在进化过程中对我们基因组的结构产生巨大影响。因此，我们建议通过开发新颖的计算机算法、基因组分析工具和严格的实验方法，对人类重复 DNA 的三个不同方面进行首次全基因组调查和分析。 1）我们建议识别和表征人类反向DNA重复序列的完整目录，这些重复序列与许多重要的基因组功能相关，例如DNA复制、减数分裂交叉和基因转换。我们的结果表明，人类 X 染色体含有大量含有睾丸基因的高度同源的反向重复序列。 2) 我们建议研究含有人类转座子的新型串联重复“卫星”DNA。它们主要在染色体的着丝粒周围区域组织成多个大型阵列，在那里发生快速的染色体进化。我们已经鉴定并鉴定了一个串联重复大家族，该家族几乎完全由重排的 MaLR LTR 转座子组成，这些转座子存在于 8 条不同的人类染色体上，阵列大小高达 70kb。 3）我们建议通过分析大量嵌套的转座子簇（其中较新的TE已转座为较旧的TE），对人类转座元件（TE）进行全基因组分析。我们开发了独特的方法和计算机算法，可以在人类基因组中定位和索引所有此类转座子簇，并可以推导出人类 TE 在进化过程中的相对时间顺序。这代表了一种研究分子进化的全新方法，该方法不依赖于恒定突变率（分子钟）的假设。本申请中提出的研究将促进基因组学的计算和生物学方法，并为我们 DNA 序列的大部分且相对被忽视的部分提供独特的分析。